KR20230110271A - 식물성 칸나비노이드들의 생산에 사용하기 위한 개선된 활성을 갖는 올리베톨산 시클라아제 변이체들 - Google Patents

식물성 칸나비노이드들의 생산에 사용하기 위한 개선된 활성을 갖는 올리베톨산 시클라아제 변이체들 Download PDF

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KR20230110271A
KR20230110271A KR1020237017474A KR20237017474A KR20230110271A KR 20230110271 A KR20230110271 A KR 20230110271A KR 1020237017474 A KR1020237017474 A KR 1020237017474A KR 20237017474 A KR20237017474 A KR 20237017474A KR 20230110271 A KR20230110271 A KR 20230110271A
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티모시 에스. 리아오
레티안 송
루이스 홈
커티스 월튼
다니엘 펄롱
민디 멜가르
데반시 바르가바
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히야신스 바이오로지컬스 아이엔씨.
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Abstract

본 발명은 일반적으로 올리베톨산 및 식물성 칸나비노이드의 생산을 위한 방법, 단리된 폴리펩티드 및 폴리뉴클레오티드, 발현 벡터, 및 숙주 세포에 관한 것이다. 올리베톨산(OVLa)을 생산하거나 식물성 칸나비노이드를 생산하는 능력을 갖는 이종 숙주 세포에서 올리베톨산(OVLa) 및/또는 식물성 칸나비노이드를 생산하는 방법은 야생형 올리베톨산 시클라아제(OAC) 단백질에 대해 적어도 6개의 아미노산 돌연변이들을 갖는 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 뉴클레오티드로 숙주 세포를 형질전환시키는 단계, 및 상기 형질전환된 숙주 세포를 배양하여 올리베톨산(OVLa) 및/또는 이로부터 유래된 식물성 칸나비노이드를 생산하는 단계를 포함한다. 상기 변이체 올리베톨산 시클라아제(OAC) 단백질(서열 번호: 92)은 야생형 올리베톨산 시클라아제(OAC) 단백질(서열 번호: 91)과 적어도 85%의 서열 동일성을 갖는다. 개선된 올리베톨산(OVLa) 또는 식물성 칸나비노이드 생산 능력을 갖는 예시적인 변이체들이 기재되어 있다.

Description

식물성 칸나비노이드들의 생산에 사용하기 위한 개선된 활성을 갖는 올리베톨산 시클라아제 변이체들
관련 출원에 대한 교차 참조
본 출원은 2020년 11월 20일에 출원된 미국 특허 출원 일련 번호 16/953,638의 이익 및 이에 대한 우선권을 주장하며, 이의 전체 내용은 본원에 참조로 포함된다.
분야
본 발명은 일반적으로 식물성 칸나비노이드(phytocannabinoid)의 생산에 유용한 올리베톨산 시클라아제(olivetolic acid cyclase) 활성을 갖는 단백질에 관한 것이다.
식물성 칸나비노이드는 칸나비스 사티바(Cannabis sativa) 식물에서 생산되는 100가지가 넘는 서로 다른 공지된 구조들을 갖는 화합물들의 큰 부류이다. 식물성 칸나비노이드는 칸나비스 사티바에서 생합성되거나, 또는 칸나비스 사티바에서 생합성된 식물성 칸나비노이드의 열분해나 다른 분해과정으로부터 생성될 수 있는 것으로 알려져 있다. 테트라하이드로칸나비놀(tetrahydrocannabinol; THC) 및 칸나비디올(cannabidiol; CBD)과 같은 이러한 생체 활성 분자들은 의료 및 레크리에이션 목적으로 식물 소재에서 추출될 수 있다. 하지만, 식물 소재의 합성은 비용이 많이 들고, 대량으로 쉽게 확장될 수 없으며, 충분한 양의 식물성 칸나비노이드를 생산하려면 긴 성장 기간이 필요하다. 칸나비스 사티바 식물은 곡물, 섬유, 및 기타 소재의 귀중한 공급원이기도 하지만, 특히나 실내에서 식물성 칸나비노이드를 생산하기 위해 칸나비스 사티바를 재배하는 것은 에너지와 노동력 측면에서 비용이 많이 든다. 칸나비스 사티바 식물에서 식물성 칸나비노이드의 후속 추출, 정제, 및 분별에도 많은 노동력과 에너지가 필요하다.
식물성 칸나비노이드는 칸나비스 사티바의 의학적 및 향정신성 효과의 원인이 되는 약리학적 활성 분자이다. 칸나비스 사티바 식물에서 식물성 칸나비노이드를 생합성하는 것은 다른 농업 프로젝트들과 유사하게 확장된다. 다른 농업 프로젝트들과 마찬가지로, 칸나비스 사티바를 재배하여 식물성 칸나비노이드를 대규모로 생산하는 것은 다양한 투입물들(예를 들어, 영양분, 빛, 해충 방제, CO 등)이 필요하다. 칸나비스 사티바를 재배하는 데 필요한 투입물들은 반드시 제공되어야 한다. 또한, 칸나비스 사티바를 재배하는 것는, 허용된다 해도, 현재 엄격한 규제, 과세, 및 상기 식물에서 제조된 산물이 상업용으로 사용되는 경우에 엄격한 품질 관리의 대상이 되므로, 비용을 더욱 증가시킨다.
식물성 칸나비노이드 유사체는 식물성 칸나비노이드와 구조적으로 유사한 약리학적 활성 분자이다. 식물성 칸나비노이드 유사체는 흔히 화학적으로 합성되는데, 이는 많은 노동력이 필요하고, 비용이 많이 들 수 있다. 이에 따라, 견고하고 확장가능하며, 발효가능한 유기체에서 식물성 칸나비노이드 및 식물성 칸나비노이드 유사체를 제조하는 것이 경제적일 수 있다. 사카로마이세스 세레비시아에(Saccharomyces cerevisiae)는 유사한 분자들의 산업적 규모 생산에 사용된 발효가능한 유기체의 일 예이다.
자연적으로 발생하는 식물성 칸나비노이드를 생산하기 위한 칸나비스 사티바 재배에 수반되는 많은 시간, 에너지, 및 노동력은 다른 방법에 의해 식물성 칸나비노이드를 생산하기 위한 형질전환 세포주를 생산할 동기를 제공한다. 올리베톨산 및 이의 유사체를 포함한 폴리케티드(polyketide)는 식물성 칸나비노이드의 귀중한 전구체이다.
식물성 칸나비노이드의 생산, 및/또는 중간체 또는 전구체 화합물로서 식물성 칸나비노이드 생합성에 유용한 화합물의 생산을 위한 대안적 효소 및 방법을 강구하는 것이 바람직하다.
올리베톨산 시클라아제(OAC) 변이체는 올리베톨산(OVLa)을 생산할 수 있는 것으로 본원에 기재되어 있다. 이러한 변이체는 이종 숙주에서 올리베톨산, 및 관련된 식물성 칸나비노이드의 생산에 유용하다. 생산 방법이 기재되어 있다. 변형된 효모 세포에서 올리베톨산 및 다운스트림 대사산물을 생산할 수 있는 기재된 OAC 변이체는 모든 숙주에 적용될 수 있으며, 식물성 칸나비노이드 생산에도 사용될 수 있다.
기재된 특정 측면에서, OAC 변이체는 야생형 효소에 대해 6개 이상의 비보존적 치환 아미노산 돌연변이들을 포함한다. 기재된 특정 OAC 변이체는 야생형 효소에 비해 개선된 활성 및/또는 개선된 올리베톨 대 올리베톨산의 비율을 나타낸다.
올리베톨산(OVLa)을 생산하거나 식물성 칸나비노이드를 생산하는 능력이 있는 이종 숙주 세포에서 올리베톨산(OVLa) 또는 이로부터 유래된 식물성 칸나비노이드를 생산하는 방법이 기재되어 있다. 상기 방법은 야생형 올리베톨산 시클라아제(OAC) 단백질에 대해 적어도 6개의 아미노산 돌연변이들을 갖는 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 뉴클레오티드로 숙주 세포를 형질전환시키는 단계, 및 상기 형질전환된 숙주 세포를 배양하여 올리베톨산 및/또는 이로부터 유래된 식물성 칸나비노이드를 생산하는 단계를 포함하며, 이때 상기 변이체 OAC 단백질은 서열 번호: 91에 기재된 야생형 OAC 단백질 서열과 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 서열 동일성을 갖는다.
서열 번호: 92와 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99% 서열 동일성을 갖는 아미노산 서열을 포함하는 올리베톨산 시클라아제 활성을 갖는 단리된 폴리펩티드가 기재되어 있으며, 이때 서열 번호: 92는 서열 번호: 91에 대해 6개 이상의 아미노산 잔기들의 돌연변이들을 포함하며, 상기 돌연변이들은 서열 번호: 91의 잔기 28, 31, 41, 43, 44, 68, 74, 84, 100, 또는 102 중 6곳 이상에 위치한다.
다음을 포함하는 단리된 폴리뉴클레오티드가 기재되어 있다: (a) 서열 번호: 3 내지 서열 번호: 39에 기재된 뉴클레오티드 서열; (b) (a)의 뉴클레오티드 서열과 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99% 동일성을 갖는 뉴클레오티드 서열, 또는 (c) (a)의 서열을 갖는 뉴클레오티드의 상보적 가닥과 하이브리드화되는 뉴클레오티드 서열. 상기 폴리뉴클레오티드를 포함하는 발현 벡터, 및 이러한 발현 벡터로 형질전환된 숙주 세포가 기재되어 있다.
본 발명의 다른 측면들과 특징들은 첨부된 도면들과 함께 구체적인 구현예들에 대한 하기의 설명을 검토할 때 당업자에게 명백해질 것이다.
이제, 본 발명의 구현예들을 첨부된 도면들을 참조하여 설명할 것이지만, 이러한 구현예들은 예시로만 제공되는 것이다.
도 1칸나비스 사티바에서 칸나비노이드 생합성 경로를 도시한 것이다.
도 2는 출원인의 동시 계류중인 국제 출원 번호 PCT/CA2020/050687에 기재된 칸나비노이드 생합성 경로를 도시한 것이다.
도 3은 부위 포화 돌연변이유발(site-saturation mutagenesis) 프로토콜에 사용되는 PCR 프라이머를 도시한 것이다.
도 4는 조합 라이브러리(combinatorial library) 구축을 위해 돌연변이유발 올리고뉴클레오티드를 조립하는 데 사용된 중첩 확장(overlap-extension) 접근법을 도시한 것이다. 기호 x는 점 돌연변이를 나타낸다.
도 5는 돌연변이 OAC 변이체를 사용한 올리베톨산 생산 결과를 도시한 것이다.
올리베톨산(OVLa) 또는 이로부터 생산된 식물성 칸나비노이드를 생산하는 방법이 본원에 기재되어 있다. 올리베톨산(OVLa)을 생산하거나 식물성 칸나비노이드를 생산하는 능력을 포함하는 이종 숙주 세포는 야생형 올리베톨산 시클라아제(OAC) 단백질에 대해 적어도 6개의 아미노산 돌연변이를 갖는 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 뉴클레오티드로 형질전환되고, 상기 형질전환된 숙주 세포를 배양하여 올리베톨산 및/또는 이로부터 유래된 식물성 칸나비노이드를 생산하며, 이때 상기 변이체 OAC 단백질은 서열 번호: 91에 기재된 야생형 OAC 단백질 서열과 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 서열 동일성을 갖는다. 예시적인 변이체 단백질은 기재된 방법에 따라 야생형에 비해 개선된 올리베톨산(OVLa) 또는 식물성 칸나비노이드 생산을 초래할 수 있다.
일부 구현예에서, OAC 단백질의 적어도 6개의 아미노산 돌연변이들 중 적어도 4개의 돌연변이들은 야생형 OAC 단백질(서열 번호: 91)의 잔기 28, 31, 41, 43, 44, 68, 74, 84, 100 또는 102에 있으며, 다른 돌연변이들은 상기 서열의 다른 곳에 위치한다. 잔기 28, 31, 41, 43, 44, 68, 74, 84, 100, 또는 102에 돌연변이가 존재하는 경우, 이는 보존적 또는 비보존적 아미노산 치환일 수 있지만, 비보존적 아미노 치환이 유리할 수 있다. 6개 아미노산 돌연변이들 중 적어도 4개의 돌연변이들이 특정 잔기 위치들에 존재하지만, 예시적 구현예에서는 4개 초과의 돌연변이들이 특정 잔기에 존재할 수 있으며, 예를 들어, 아미노산 돌연변이들 중 6, 7, 8, 9 또는 10개의 돌연변이들이 야생형 서열에 대해 28, 31, 41, 43, 44, 68, 74, 84, 100, 또는 102번 위치들에서 발견될 수 있다. 특정 구현예에서, 잔기 28, 31, 41, 43, 44, 68, 74, 84, 100 또는 102에 위치한 돌연변이들 이외의 돌연변이들은 보존적 아미노산 치환으로 제한될 수 있으므로 변이체 OAC 단백질은 야생형 OAC 단백질과 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99% 서열 동일성을 유지한다.
상기 방법은 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 뉴클레오티드로 숙주 세포를 형질전환하는 것을 포함할 수 있으며, 상기 뉴클레오티드는 (a) 서열 번호: 3 내지 서열 번호: 39에 기재된 뉴클레오티드 서열; (b) (a)의 서열과 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99% 동일성을 갖는 뉴클레오티드 서열; 또는 (c) (a)의 서열을 갖는 뉴클레오티드의 상보적 가닥과 하이브리드화되는 뉴클레오티드 서열을 포함한다. 예를 들어, 변이체 OAC 단백질은 서열 번호: 40 내지 서열 번호: 76 중 어느 하나에 따른 서열을 포함할 수 있다.
특정 구현예에서, 야생형 OAC 단백질에 대한 적어도 6개의 아미노산 돌연변이 중 적어도 4개는 다음으로 이루어진 그룹으로부터 선택된다: V28A; V31G; Y41T, Y41S 또는 Y41V; K44V; T68L 또는 T68R; I74E, I74R, I74D 또는 I74G; V84R; R100M 또는 R100E; 및 G102R, G102S, 또는 G102STOP. 예를 들어, 일부 구현예에서는 야생형에 대한 적어도 10개, 적어도 9개, 적어도 8개, 적어도 7개, 적어도 6개, 또는 적어도 5개의 이들 아미노산 돌연변이들이 존재할 수 있다.
상기 방법에서, 형질전환된 숙주 세포에 의한 식물성 칸나비노이드의 생산은 칸나비게롤(cannabigerol; CBG), 칸나비게롤산(cannabigerolic acid; CBGa), 칸나비게로바린(cannabigerovarin; CBGV), 칸나비게로바린산(cannabigerovarinic acid; CBGVa), 칸나비게로신(cannabigerocin; CBGO), 칸나비게로신산(cannabigerocinic acid; CBGOa), 칸나비바린(cannabivarin), 테트라하이드로칸나비놀(THC), 또는 테트라하이드로칸나비놀산(tetrahydrocannabinolic acid; THCa)을 포함하나 이에 제한되지 않는 식물성 칸나비노이드의 생산을 수반할 수 있다. 또한, 기재된 OAC 변이체를 사용하여, 숙주 세포 내의 디바린산 신타아제(divarinic acid synthase)와 함께 숙주 세포는 칸나비바린, 예를 들어 디바린산을 생산할 수 있다.
상기 숙주 세포는 올리베톨산 시클라아제(OAC) 야생형(서열 번호: 91)으로부터 표시된 치환들이 존재하는 다음 서열들 중 어느 하나의 서열과 적어도 85%, 적어도 90%, 적어도 95%, 적어도 99%, 또는 100% 서열 동일성을 갖는 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 뉴클레오티드로 형질전환될 수 있다:
V28A/V31G/Y41S/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102R (서열 번호: 42),
V28A/Y41T/G43SILENT(=GGG)/T68L/I74E/V84R/R100M/G102R (서열 번호: 40),
Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R (서열 번호: 41),
V28A/Y41T/G43SILENT(=GGG)/T68L/I74G/V84R/R100E (서열 번호: 43),
V28A/Y41T/G43SILENT(=GGG)/K44V/T68L/I74D/V84R/R100M/G102R (서열 번호: 44),
V28A/Y41T/G43SILENT(=GGG)/T68L/I74D/V84R/G102R (서열 번호: 45),
V28A/Y41T/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102R (서열 번호: 46),
Y41T/G43SILENT(=GGG)/T68R/I74R/V84R/R100M/G102STOP (서열 번호: 47),
V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/R100E/G102R (서열 번호: 48),
V28A/Y41T/G43SILENT(=GGG)/K44V/T68R/I74G/V84R/G102STOP (서열 번호: 49),
V28A/Y41T/G43SILENT(=GGG)/K44V/T68R/I74G/V84R/G102STOP (서열 번호: 50),
V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74E/V84R/R100E (서열 번호: 51),
V28A/Y41S/G43SILENT(=GGG)/T68R/I74R/V84R/R100M/G102STOP (서열 번호: 52),
Y41T/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/G102R (서열 번호: 53),
V28A/Y41T/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100E/G102R (서열 번호: 54),
V28A/V31G/Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R (서열 번호: 55),
V28A/G43SILENT(=GGG)/K44V/I74D/V84R/R100E/G102R(=CGC) (서열 번호: 56),
V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/G102R (서열 번호: 57),
Y41T/G43SILENT(=GGG)/T68L/I74G/V84R/R100M/G102R (서열 번호: 58),
V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100E/G102R (서열 번호: 59),
V31G/Y41S/G43SILENT(=GGG)/K44V/T68R/V84R/R100E (서열 번호: 60),
V28A/Y41V/G43SILENT(=GGG)/T68L/I74D/R100E/G102STOP (서열 번호: 61)
V28A/Y41V/G43SILENT(=GGG)/T68R/I74G/V84R/R100M/G102R (서열 번호: 62),
V31G/G43SILENT(=GGG)/I74G/V84R/R100E (서열 번호: 63),
V28A/Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100M/G102R (서열 번호: 64),
V28A/V31G/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R (서열 번호: 65),
V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/R100M/G102R (서열 번호: 66),
V28A/V31G/G43SILENT(=GGG)/T68L/I74R/V84R/R100E/G102R (서열 번호: 67),
V31G/Y41V/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102STOP (서열 번호: 68),
V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74D/V84R/G102R (서열 번호: 69),
V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74D/V84R/R100E/G102R (서열 번호: 70),
V28A/Y41S/G43SILENT(=GGG)/K44V/T68R/I74G/V84R/R100M/G102R (서열 번호: 71),
V28A/Y41V/G43SILENT(=GGG)/K44V/I74R/R100E/G102STOP (서열 번호: 72),
V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/I74E/V84R/R100M/G102R (서열 번호: 73),
V28A/G43SILENT(=GGG)/K44V/T68R/I74E/V84R/R100E/G102STOP (서열 번호: 74),
V31G/Y41T/G43SILENT(=GGG)/K44V/T68L/I74D/V84R/G102R (서열 번호: 75), 또는
Y41V/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/G102R (서열 번호: 76).
기재된 방법에서 형질전환된 숙주 세포는 박테리아 세포, 진균 세포, 원생생물 세포, 또는 식물 세포일 수 있다. 예시적인 유기체로는 사카로마이세스 세레비시아에, 에스케리키아 콜라이(E. coli), 야로위아 리폴리티카(Yarrowia lipolytica), 또는 코마가타엘라 파피(Komagataella phaffii), 뿐만 아니라 본원에 기재된 다른 유기체들이 포함된다. 형질전환된 숙주 세포는 식물성 칸나비노이드 생산에 유용한 다른 효소를 추가로 포함하거나 상기 효소로 형질전환될 수 있다. 예를 들어, 폴리케티드 신타아제 효소를 암호화하는 폴리뉴클레오티드 및/또는 프레닐트랜스퍼라아제(prenyltransferase) 효소를 암호화하는 폴리뉴클레오티드도 숙주 세포에 포함될 수 있다. 출원인의 동시 계류중인 국제 출원 번호 PCT/CA2020/050687(본원에 참조로 포함됨)에 기재된 것과 같은 폴리뉴클레오티드 및 방법에 대한 추가 옵션이 고려된다.
올리베톨산 시클라아제(OAC) 활성을 갖는 단리된 폴리펩티드가 본원에 기재되어 있다. 상기 폴리펩티드 활성은 서열 번호: 92에 기재된 아미노산 서열을 포함하며, 이때 서열 번호: 92는 서열 번호: 91(야생형 OAC)에 대해 6개 이상의 아미노산 잔기들의 돌연변이들을 포함하며, 상기 돌연변이들은 서열 번호: 91의 잔기 28, 31, 41, 43, 44, 68, 74, 84, 100, 또는 102에 있다. 상기 단리된 폴리펩티드는 서열 번호: 40 내지 서열 번호: 76 중 하나에 기재된 아미노산 서열을 가질 수 있다.
(a) 서열 번호: 3 내지 서열 번호: 39에 기재된 뉴클레오티드 서열; (b) (a)의 뉴클레오티드 서열과 적어도 85% 동일성을 갖는 뉴클레오티드 서열; 또는 (c) (a)의 서열을 갖는 뉴클레오티드의 상보적 가닥과 하이브리드화되는 뉴클레오티드 서열;을 가질 수 있는 단리된 폴리뉴클레오티드가 기재되어 있다.
야생형 올리베톨산 시클라아제(OAC) 단백질에 대해 6개 이상의 아미노산 돌연변이들이 존재하는 서열 번호: 92의 서열을 갖는 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 폴리뉴클레오티드를 포함하는 발현 벡터가 기재되어 있다. 이러한 발현 벡터에서, 변이체 OAC 단백질을 암호화하는 폴리뉴클레오티드는 서열 번호: 3 내지 서열 번호: 39 중 어느 하나의 서열과 적어도 85%의 서열 동일성을 가질 수 있다.
상기 기재된 발현 벡터로 형질전환된 숙주 세포도 본원에 포함된다. 이러한 숙주 세포는 추가로 폴리케티드 신타아제 효소 및/또는 프레닐트랜스퍼라아제 효소를 암호화하는 폴리뉴클레오티드와 같이 올리베톨산 및/또는 식물성 칸나비노이드의 합성에 유용한 다른 효소를 암호화하는 폴리뉴클레오티드를 포함할 수 있다. 이러한 숙주 세포는 박테리아 세포, 진균 세포, 원생생물 세포, 또는 식물 세포, 예를 들어, 사카로마이세스 세레비시아에, 에스케리키아 콜라이, 야로위아 리폴리티카, 또는 코마가타엘라 파피일 수 있다.
정의
본원에 사용된 특정 용어들은 아래에 설명되어 있다.
본원에 사용된 "칸나비노이드"라는 용어는 칸나비노이드 수용체에서 직접 또는 간접적인 활성을 나타내는 화학적 화합물을 지칭한다. 칸나비노이드의 비제한적 예로는 테트라하이드로칸나비놀(THC), 칸나비디올(CBD), 칸나비놀(CBN), 칸나비게롤(CBG), 칸나비크로멘(cannabichromene; CBC), 칸나비시클롤(cannabicyclol; CBL), 칸나비바린(CBV), 테트라하이드로칸나비바린(THCV), 칸나비디바린(cannabidivarin; CBDV), 칸나비크로메바린(cannabichromevarin; CBCV), 칸나비게로바린(CBGV), 및 칸나비게롤 모노메틸 에테르(cannabigerol monomethyl ether; CBGM)가 포함된다.
본원에 사용된 "식물성 칸나비노이드"라는 용어는 식물 종에서 일반적으로 발생하는 칸나비노이드를 지칭한다. 본 발명에 따라 생산되는 예시적인 식물성 칸나비노이드로는 칸나비게롤(CBG), 칸나비게롤산(CBGa), 칸나비게로바린(CBGV), 칸나비게로바린산(CBGVa), 칸나비게로신(CBGo), 또는 칸나비게로신산(CBGoa)이 포함된다.
칸나비노이드 및 식물성 칸나비노이드는 하나 이상의 카복실산 작용기가 포함되거나 결여되어 있을 수 있다. 카복실산 작용기를 포함하는 이러한 칸나비노이드 또는 식물성 칸나비노이드, 또는 식물성 칸나비노이드의 비제한적 예로는 테트라하이드로칸나비놀산(THCA), 칸나비디올산(cannabidiolic acid; CBDA), 및 칸나비크로멘산(cannabichromenic acid; CBCA)이 포함된다.
"동족체(homologue)"라는 용어는 반드시 생물학적 기원을 언급하지 않고, 동일한 종 및 다른 종으로부터의 상동성(homologous) 서열들과 동일한 종 및 다른 종으로부터의 이종상동성(orthologous) 서열들을 포함한다. 상동성을 갖는 서로 다른 폴리뉴클레오티드들 또는 폴리펩티드들을 동족체로 지칭할 수 있다.
"상동성(homology)"이라는 용어는 반드시 유전적 기원에 관련되지 않고, 위치 동일성(즉, 서열 유사성 또는 동일성)의 비율 관점에서 2개 이상의 폴리뉴클레오티드 및/또는 폴리펩티드 서열들 간의 유사성 수준을 지칭할 수 있다. 또한, 상동성은 서로 다른 폴리뉴클레오티드 또는 폴리펩티드들 간에 유사한 기능적 특성들에 대한 개념을 의미한다. 따라서, 본원의 조성물과 방법은 본원에 기재된 폴리펩티드와 폴리뉴클레오티드 서열들에 대한 동족체를 추가로 포함할 수 있다.
본원에 사용된 "이종상동성"이라는 용어는, 종분화 동안 공통 조상 유전자에서 발생한 서로 다른 종들에서의 상동성 폴리펩티드 서열들 및/또는 폴리뉴클레오티드 서열들을 지칭한다.
본원에서 사용된 바와 같은 "동족체"는 본원의 폴리뉴클레오티드 서열들과 유의미한 서열 동일성(예를 들어, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 및/또는 100%)을 갖는, 동일성 백분율이나 상동성 백분율로 언급되든 간에, 특정 기능성을 갖는 서열일 수 있다.
본원에 사용된 "서열 동일성(sequence identity)"은 최적으로 정렬된 2개의 폴리뉴클레오티드 또는 펩티드 서열들이 구성요소들, 예를 들어 뉴클레오티드들 또는 아미노산들의 정렬 범위(window of alignment) 전체에 걸쳐 변하지 않는 정도를 지칭한다. "동일성"은 공지된 방법들에 의해 쉽게 계산될 수 있다.
본원에 사용된 "서열 동일성 백분율" 또는 "동일성 백분율"이라는 용어는 2개의 서열들이 최적으로 정렬될 때, 테스트("대상") 폴리뉴클레오티드 분자(또는 이의 상보적 가닥)와 비교하여 기준 ("쿼리(query)") 폴리뉴클레오티드 분자(또는 이의 상보적 가닥)의 선형 폴리뉴클레오티드 서열 내 동일한 뉴클레오티드들의 백분율을 의미한다. 일부 구현예에서, "동일성 백분율"은 아미노산 서열 내 동일한 아미노산들의 백분율을 의미할 수 있다.
본원에 사용된 "지방산-CoA", "지방 아실-CoA" 또는 "CoA 공여체"라는 용어들은, 연장 단위(extender unit)(예를 들어, 말로닐-CoA)와 축합 반응으로 반응하여 폴리케티드를 형성하는 프라이머 분자로서 폴리케티드 합성에서 유용한 화합물을 지칭한다. 본원에 기재된 합성 경로들에 유용한 지방산-CoA 분자들(본원에서는 프라이머 분자들 또는 CoA 공여체들이라고도 지칭함)의 예로는 아세틸-CoA, 부티릴-CoA, 헥사노일-CoA가 포함되지만, 이에 제한되지는 않는다. 이러한 지방산-CoA 분자들은 숙주 세포에 제공될 수 있거나, 또는 본원에 기재된 바와 같이 폴리케티드의 생합성을 위한 숙주 세포에 의해 합성될 수도 있다.
2개의 뉴클레오티드 서열들은 2개의 해당 서열들이 엄격한 조건 하에 서로 하이브리드화되는 경우에 실질적으로 "상보적"인 것으로 간주될 수 있다. 일부 예에서, 실질적으로 상보적인 것으로 간주되는 2개의 뉴클레오티드 서열들은 매우 엄격한 조건 하에 서로 하이브리드화된다.
예를 들어, 서던 하이브리드화(Southern hybridization) 및 노던 하이브리드화(Northern hybridization)에서 핵산 하이브리드화 실험과 관련하여 "엄격한 하이브리드화 조건" 및 "엄격한 하이브리드화 세척 조건"이라는 용어들은 서열에 따라 달라지며, 서로 다른 환경 파라미터들에 따라 다르다. 일부 예에서, 일반적으로, 매우 엄격한 하이브리드화 및 세척 조건은 규정된 이온 강도와 pH에서 특정 서열에 대한 열 융점(Tm)보다 약 5℃ 더 낮도록 선택된다.
일부 예로서, 폴리뉴클레오티드는 본원에 기재된 임의의 기준 서열과 적어도 약 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% 또는 100%의 서열 동일성을 갖는 폴리뉴클레오티드 또는 "변이체"를 포함하는데, 이때 일반적으로 상기 변이체는 기준 서열의 적어도 하나의 생물학적 활성을 유지한다.
본원에 사용된 "폴리뉴클레오티드 변이체" 및 "변이체" 등의 용어들은 기준 폴리뉴클레오티드 서열과 실질적인 서열 동일성을 나타내는 폴리뉴클레오티드, 또는 기준 서열과, 예를 들어, 엄격한 조건 하에 하이브리드화하는 폴리뉴클레오티드를 지칭한다. 이러한 용어들은 하나 이상의 뉴클레오티드들이 부가 또는 결실되었거나, 또는 기준 폴리뉴클레오티드와 다른 뉴클레오티드로 치환된 폴리뉴클레오티드들도 포함할 수 있다. 돌연변이, 부가, 결실, 및 치환을 포함하는 특정한 변형이 기준 폴리뉴클레오티드에 이루어질 수 있고, 이에 의해 변형된 폴리뉴클레오티드도 기준 폴리뉴클레오티드의 생물학적 기능이나 활성을 유지하고 있음을 이해할 것이다.
일부 예에서, 본원에 기재된 폴리뉴클레오티드가 "벡터" 및/또는 "발현 카세트" 내에 포함될 수 있다.
일부 구현예에서, 본원에 기재된 뉴클레오티드 서열 및/또는 핵산 분자는 숙주 세포에서의 발현을 위해 다양한 프로모터들에 "작동가능하게(operably)" 또는 "작동적으로(operatively)" 연결될 수 있다. 따라서, 일부 예에서, 본 발명은 형질전환된 숙주 세포 및 상기 형질전환된 숙주 세포를 포함하는 형질전환된 유기체를 제공하는데, 이때 상기 숙주 세포와 유기체는 본 발명의 하나 이상의 핵산 분자/뉴클레오티드 서열로 형질전환된다. 본원에서 사용된 바와 같이, 제2 핵산 서열에 작동가능하게 연결된 제1 핵산 서열을 언급하는 경우에 "~에 작동가능하게 연결된(operably linked to)"이란 상기 제1 핵산 서열이 상기 제2 핵산 서열과 기능적 관계에 놓여 있는 상황을 의미한다. 예를 들어, 프로모터가 코딩 서열의 전사 또는 발현에 영향을 미치는 경우라면, 해당 프로모터는 상기 코딩 서열에 작동가능하게 연결되어 있는 것이다.
폴리펩티드와 관련하여, 제2 폴리펩티드 서열에 작동가능하게 연결된 제1 폴리펩티드 서열을 언급하는 경우에 "~에 작동가능하게 연결된"이란 상기 제1 폴리펩티드 서열이 제2 폴리펩티드 서열과 기능적 관계에 놓여 있는 상황을 의미한다.
본원에 사용된 "프로모터"라는 용어는 프로모터와 작동가능하게 연결되어 있는 뉴클레오티드 서열(즉, 코딩 서열)의 전사를 제어 또는 조절하는 뉴클레오티드 서열을 지칭한다. 통상적으로, "프로모터"란 RNA 중합효소 II에 대한 결합 부위를 포함하여 전사의 개시를 지시하는 뉴클레오티드 서열을 지칭한다. 일반적으로, 프로모터는 5', 또는 상응하는 코딩 서열의 코딩 영역의 개시 지점에 대해 업스트림에서 발견된다. 프로모터 영역은 유전자 발현의 조절자로서 작용하는 다른 요소들을 포함할 수 있다.
프로모터는, 예를 들어, 재조합 핵산 분자, 즉 키메라 유전자의 제조에 사용하기 위한 구성적(constitutive), 유도성, 시간적으로 조절되고(temporally regulated), 발달적으로 조절되며, 화학적으로 조절되고, 조직 선호되며, 조직 특이적인 프로모터를 포함할 수 있다.
프로모터의 선택은 발현을 위한 시간적 및 공간적 요건과 형질전환될 숙주 세포에 따라 달라질 것이다. 따라서, 예를 들어, 자극에 대한 반응으로 발현이 요구되는 경우, 자극 또는 화학물질에 의해 유도될 수 있는 프로모터가 사용될 수 있다. 유기체의 세포 또는 조직 전반에 걸쳐서 상대적으로 일정한 수준의 지속적인 발현이 요구되는 경우, 구성적 프로모터가 선택될 수 있다.
일부 예에서는 벡터가 사용될 수 있다.
일부 예에서, 본원에 기재된 폴리뉴클레오티드 분자 및 뉴클레오티드 서열은 벡터와 연결되어 사용될 수 있다.
"벡터"라는 용어는 핵산 또는 폴리뉴클레오티드를 숙주 세포로 옮기거나, 전달하거나 또는 도입하기 위한 조성물을 지칭한다. 벡터는 옮겨지거나, 전달되거나, 또는 도입될 뉴클레오티드 서열(들)을 포함하는 폴리뉴클레오티드 분자를 포함할 수 있다. 일반적인 부류의 벡터들의 비제한적 예로는 바이러스 벡터, 플라스미드 벡터, 파지 벡터, 파지미드 벡터, 코스미드, 포스미드, 박테리오파지, 또는 인공 염색체가 포함되지만, 이에 제한되지는 않는다. 벡터의 선택은 바람직한 형질전환 기술과 형질전환을 위한 표적 종에 따라 달라질 것이다.
본원에서 사용되는 바와 같은 "발현 벡터"는 목적하는 뉴클레오티드 서열을 포함하는 핵산 분자를 지칭하는데, 이때 상기 뉴클레오티드 서열은 적어도 제어 서열(예를 들어, 프로모터)과 작동적으로 연결되어 있다. 따라서, 일부 예에서는 본원에 기재된 폴리뉴클레오티드 서열을 발현하도록 설계된 발현 벡터가 제공된다.
목적하는 폴리뉴클레오티드 서열을 포함하는 발현 벡터는 "키메라성"일 수 있는데, 이는 이의 구성요소들 중 적어도 하나가 이의 다른 구성요소들 중 적어도 하나에 대해 이종임을 의미한다. 발현 카세트는, 자연 발생적인 것이지만 이종 발현에 유용한 재조합 형태로 수득된 것일 수도 있다. 그러나, 일부 예에서, 발현 벡터는 숙주에 대해 이종성이다. 예를 들어, 발현 벡터의 특정 폴리뉴클레오티드 서열은 숙주 세포에서는 자연적으로 발생하지 않아, 형질전환 작업에 의해 숙주 세포 또는 숙주 세포의 조상에게 도입되어야 한다.
일부 예에서, 발현 벡터는 다른 조절 서열들을 포함할 수도 있다. 본원에 사용된 "조절 서열"이란 코딩 서열의 업스트림(5' 비코딩 서열), 코딩 서열 내 또는 코딩 서열의 다운스트림(3' 비코딩 서열)에 위치하여, 연결되어 있는 코딩 서열의 전사, RNA 프로세싱 또는 안정성, 또는 번역에 영향을 미치는 뉴클레오티드 서열을 의미한다. 조절 서열에는 프로모터, 인핸서, 인트론, 5' 및 3' 비번역 영역, 번역 리더 서열, 종결 신호, 및 폴리아데닐화 신호 서열이 포함되지만, 이에 제한되지는 않는다.
발현 벡터는 형질전환된 숙주 세포를 선택하는 데 사용될 수 있는 선별가능한 마커에 대한 뉴클레오티드 서열을 포함할 수도 있다.
본원에 사용된 "선별가능한 마커"란, 발현될 때 해당 마커를 발현하는 숙주 세포에 뚜렷하게 구분되는 표현형을 제공함으로써, 이러한 형질전환된 숙주 세포가 마커를 갖지 않는 세포와 구별될 수 있도록 해주는 뉴클레오티드 서열을 의미한다. 이러한 뉴클레오티드 서열은, 해당 마커가 화학적 수단에 의해, 예를 들어 선택적 제제(예를 들어, 항생제, 당, 탄소 공급원 등)를 사용함으로써 선택될 수 있는 특징을 부여하는지, 또는 해당 마커가 단순히 관찰 또는 테스트를 통해, 예를 들어 스크리닝에 의해 식별될 수 있는 특징인지에 따라, 선별가능한 마커 또는 스크리닝가능한 마커를 암호화할 수 있다. 적합한 선별가능한 마커의 예시는 당업계에 공지되어 있으며, 본원에 기재된 발현 벡터에 사용될 수 있다.
벡터 및/또는 발현 벡터 및/또는 폴리뉴클레오티드가 세포 내로 도입될 수 있다.
목적하는 뉴클레오티드 서열(예를 들어, 핵산 분자/작제물/발현 벡터)의 맥락에서 "도입하는(introducing)"이라는 용어는, 해당 뉴클레오티드 서열이 세포의 내부에 접근할 수 있는 방식으로 목적하는 뉴클레오티드 서열을 숙주 세포에 제공하는 것을 의미한다. 하나 이상의 뉴클레오티드 서열이 도입되는 경우, 이러한 뉴클레오티드 서열들은 하나의 폴리뉴클레오티드 또는 핵산 작제물의 일부로서, 또는 개별 폴리뉴클레오티드 또는 핵산 작제물로서 조립될 수 있고, 동일하거나 상이한 형질전환 벡터 상에 위치할 수 있다. 따라서, 이러한 폴리뉴클레오티드들은 하나의 형질전환 작업, 또는 개별 형질전환 작업으로 숙주 세포 내에 도입될 수 있다.
본원에 사용된 "접촉하는(contacting)"이라는 용어는, 예를 들어, 화합물이 세포에 전달될 수 있는 과정을 가리킨다. 상기 화합물은, 세포 내로의(즉, 세포내) 직접 도입 및/또는 공동(cavity), 간질 공간(interstitial space) 내로, 또는 유기체의 순환계 내로의 세포외 도입을 포함하지만, 이에 제한되지 않는 다양한 방식으로 투여될 수 있다.
본원에 사용된 "형질전환" 또는 "형질감염"이라는 용어는 폴리뉴클레오티드 또는 이종 핵산을 세포 내로 도입하는 것을 의미한다. 세포의 형질전환은 안정적이거나 일시적일 수 있다.
폴리뉴클레오티드와 관련하여 본원에 사용된 "일시적 형질전환"이라는 용어는 세포 내로 도입되었지만 해당 세포의 게놈에 통합되지 않는 폴리뉴클레오티드를 지칭한다.
세포 내로 도입된 폴리뉴클레오티드와 관련하여 "안정적으로 도입하는" 또는 "안정적으로 도입된"이라는 용어들은, 도입된 폴리뉴클레오티드가 해당 세포의 게놈에 안정적으로 통합되어, 세포가 폴리뉴클레오티드로 안정적으로 형질전환됨을 나타내는 것으로 의도된다.
"숙주 세포"라는 용어는 임의의 재조합 벡터(들) 또는 본 발명의 단리된 폴리뉴클레오티드의 수용체일 수 있거나 수용체였던 개별 세포 또는 세포 배양물을 포함한다. 숙주 세포는 단일 숙주 세포의 자손을 포함하는데, 그 자손은 자연적, 우발적 또는 고의적 돌연변이 및/또는 변화로 인해 반드시 본래의 모세포와 (형태상 또는 전체 DNA 보체에서) 완전히 동일하지 않을 수 있다. 숙주 세포는 본 발명의 재조합 벡터 또는 폴리뉴클레오티드로 생체내 또는 시험관내에서 형질전환된 세포를 포함한다. 본 발명의 재조합 벡터를 포함하는 숙주 세포는 재조합 숙주 세포이다.
일부 예에서, 숙주 세포는 박테리아 세포, 진균 세포, 원생생물 세포, 또는 식물 세포일 수 있다. 숙주 세포의 구체적인 예시는 하기에 기재되어 있다.
"전환"은 기질의 상응하는 산물로의 효소적 변형을 의미한다. "전환율"은 특정 조건 하에서 일정 기간 내에 기질이 산물로 전환되는 비율을 의미한다. 따라서, 예를 들어, 케토리덕타아제 폴리펩티드의 "활성" 또는 "전환율"은 기질의 산물로의 "전환율"로 표현될 수 있다.
"친수성 아미노산 또는 잔기"는 표준화된 공통 소수성 척도(normalized consensus hydrophobicity scale)(참조: Eisenberg et al., 1984)에 따라 0 미만의 소수성을 나타내는 측쇄를 갖는 아미노산 또는 잔기를 지칭한다. 유전적으로 암호화된 친수성 아미노산에는 L-Thr(T), L-Ser(S), L-His(H), L-Glu(E), L-Asn(N), L-Gln(Q), L-Asp(D), L-Lys(K) 및 L-Arg(R)가 포함된다.
"산성 아미노산 또는 잔기"는 아미노산이 펩티드 또는 폴리펩티드에 포함될 때 약 6 미만의 pKa 값을 나타내는 측쇄를 갖는 친수성 아미노산 또는 잔기를 지칭한다. 산성 아미노산은 통상적으로 수소 이온의 손실로 인해 생리적 pH에서 음전하를 띤 측쇄를 갖는다. 유전적으로 암호화된 산성 아미노산에는 L-Glu(E) 및 L-Asp(D)가 포함된다.
"염기성 아미노산 또는 잔기"는 아미노산이 펩티드 또는 폴리펩티드에 포함될 때 약 6 초과의 pKa 값을 나타내는 측쇄를 갖는 친수성 아미노산 또는 잔기를 지칭한다. 염기성 아미노산은 통상적으로 하이드로늄(hydronium) 이온과의 결합으로 인해 생리적 pH에서 양전하를 띤 측쇄를 갖는다. 유전적으로 암호화된 염기성 아미노산에는 L-Arg(R) 및 L-Lys(K)가 포함된다.
"극성 아미노산 또는 잔기"는 생리적 pH에서 하전되지 않으며, 두 개의 원자들에 의해 공유되는 전자쌍이 원자들 중 하나에 더 밀접하게 보유되는 결합을 적어도 하나 가지고 있는 측쇄를 갖는 친수성 아미노산 또는 잔기를 지칭한다. 유전적으로 암호화된 극성 아미노산에는 L-Asn(N), L-Gln(Q), L-Ser(S) 및 L-Thr(T)가 포함된다.
"소수성 아미노산 또는 잔기"는 표준화된 공통 소수성 척도(참조: Eisenberg et al., 1984)에 따라 0보다 큰 소수성을 나타내는 측쇄를 갖는 아미노산 또는 잔기를 지칭한다. 유전적으로 암호화된 소수성 아미노산에는 L-Pro(P), L-Ile(I), L-Phe(F), L-Val(V), L-Leu(L), L-Trp(W), L-Met(M), L-Ala(A), 및 L-Tyr(Y)가 포함된다.
"방향족 아미노산 또는 잔기"는 적어도 하나의 방향족 또는 헤테로방향족 환을 포함하는 측쇄를 갖는 친수성 또는 소수성 아미노산 또는 잔기를 지칭한다. 유전적으로 암호화된 방향족 아미노산에는 L-Phe(F), L-Tyr(Y) 및 L-Trp(W)가 포함된다. 헤테로방향족 질소 원자 L His(H)의 pKa로 인해, 이는 때때로 염기성 잔기로 분류되거나 측쇄가 헤테로방향족 환을 포함하므로 방향족 잔기로 분류되지만, 본원에서는 히스티딘을 친수성 잔기로 분류한다.
"제한된(constrained) 아미노산 또는 잔기"는 제한된 기하구조를 갖는 아미노산 또는 잔기를 지칭한다. 본원에서, 제한된 잔기는 L-Pro(P) 및 L-His(H)를 포함한다. 히스티딘은 상대적으로 작은 이미다졸 환을 가지고 있기 때문에 제한된 기하구조를 가지고 있다. 프롤린에는 5원 환도 있기 때문에 제한된 기하구조를 갖는다.
"비극성 아미노산 또는 잔기"는 생리적 pH에서 하전되지 않으며, 두 개의 원자에 의해 공유되는 전자쌍이 일반적으로 두 원자들 각각에 동일하게 보유되는 결합을 갖는 측쇄(즉, 측쇄는 극성이 아님)를 갖는 소수성 아미노산 또는 잔기를 지칭한다. 유전적으로 암호화된 비극성 아미노산에는 L-Gly(G), L-Leu(L), L-Val(V), L-Ile(I), L-Met(M) 및 L-Ala(A)가 포함된다.
"지방족 아미노산 또는 잔기"는 지방족 탄화수소 측쇄를 갖는 소수성 아미노산 또는 잔기를 지칭한다. 유전적으로 암호화된 지방족 아미노산에는 L-Ala(A), L-Val(V), L-Leu(L), 및 L-Ile(I)가 포함된다.
"작은 아미노산 또는 잔기"는 총 3개 이하의 탄소 및/또는 헤테로원자(α-탄소 및 수소 제외)로 구성된 측쇄를 갖는 아미노산 또는 잔기를 지칭한다. 작은 아미노산 또는 잔기는 상기 정의에 따라 지방족, 비극성, 극성, 또는 산성 작은 아미노산 또는 잔기로 더 분류될 수 있다. 유전적으로 암호화된 작은 아미노산에는 L-Ala(A), L-Val(V), L-Cys(C), L-Asn(N), L-Ser(S), L-Thr(T) 및 L-Asp(D)가 포함된다.
"보존적" 아미노산 치환(또는 돌연변이)은 어떤 잔기가 유사한 측쇄를 갖는 잔기로 치환되는 것을 의미하며, 따라서 통상적으로 폴리펩티드의 아미노산을 동일하거나 유사하게 정의되는 아미노산 부류 내에 있는 아미노산으로 치환하는 것을 포함한다. 다음 잔기들에 대해 가능한 보존적 돌연변이가 괄호 안에 표시되어 있다: A, L, V, I(기타 지방족 잔기: A, L, V, I); A, L, V, I, G, M(기타 비극성 잔기: A, L, V, I, G, M); D, E(기타 산성 잔기: D, E); K, R(기타 염기성 잔기: K, R); P, H(기타 제한된 잔기: P, H); N, Q, S, T(기타 극성 잔기: N, Q, S, T); Y, W, F(기타 방향족 잔기: Y, W, F); 및 C(없음).
식물성 칸나비노이드는 칸나비스 식물에서 생산되는 100가지가 넘는 서로 다른 공지된 구조들을 갖는 화합물들의 큰 부류이다. 테트라하이드로칸나비놀(THC) 및 칸나비디올(CBD)과 같은 이러한 생체 활성 분자들은 의료 및 향정신성 목적으로 식물 소재에서 추출될 수 있다. 하지만, 식물 소재의 합성은 비용이 많이 들고, 대량으로 쉽게 확장될 수 없으며, 충분한 양의 식물성 칸나비노이드를 생산하려면 긴 성장 기간이 필요하다. 칸나비노이드를 생산할 수 있는 사카로마이세스 세레비시아에와 같은 발효성 유기체는 이러한 화합물을 산업적 규모로 생산하는 데 있어 경제적인 경로를 제공할 것이다. 식물성 칸나비노이드를 생산하기 위한 칸나비스 사티바 재배에 수반되는 많은 시간, 에너지 및 노동력은, 효모에서 식물성 칸나비노이드를 생산하기 위한 형질전환 세포주를 생산할 동기를 제공한다. 이러한 노력의 일 예는 Mookerjee 등의 WO2018/148848의 PCT 출원에서 제공된다. 칸나비스의 방향족 프레닐트랜스퍼라아제는 Page 등의 미국 특허 번호 8,884,100에 기재되어 있다.
도 1칸나비스 사티바에서 칸나비노이드 생합성 경로를 도시한 것이다. 사카로마이세스 세레비시아에에서 칸나비스 사티바 경로의 발현 및 기능이 독성 전구체 및 열악한 발현 문제로 인해 방해를 받음에 따라, 이러한 문제를 극복하는 칸나비노이드 생산을 위한 새로운 생합성 경로가 개발되었다. 이 경로는 도 1에 설명되어 있으며, 다중 효소 시스템으로 구성된다. 딕티오스텔리움 디스코이데움(D. discoideum)의 DiPKS와 칸나비스 사티바의 OAC는 포도당에서 직접 올리베톨산을 생산하는 데 사용된다. 이어서, 효모 테르페노이드 경로의 GPP, 및 OLA가 프레닐트랜스퍼라아제를 사용하여 촉매되는 카나비게롤산으로 전환된다. 그 다음, 칸나비스 사티바 THCa 신타아제 또는 CBDa 신타아제를 사용하여 각각 THCa 또는 CBDa를 형성하기 위해 칸나비게롤산을 추가로 고리화한다.
도 2는 본 명세서에 참조로 포함된 출원인의 공동 계류중인 PCT 출원 번호 CA2020/050687(Bourgeois et al., 2019년 5월 21일 출원)에 기재된 바와 같은 칸나비노이드 생합성 경로를 도시한 것이다.
칸나비노이드 생합성 경로의 첫 번째 개입 단계는 올리베톨산의 생합성이다. 이는 딕티오스텔리움 디스코이데움의 DiPKS(Ghosh et al., 2008) 또는 칸나비스 사티바의 OAS(Taura et al., 2009)와 같은 폴리케티드 신타아제를 사용하여 수행되며, 또한 올리베톨산 시클라아제(OAC)(Gagne et al., 2012)의 사용이 필요하다. 이 과정은 말로닐-CoA 세 단위를 축합하여 선형 테트라케티드를 형성하는 폴리케티드 신타아제를 사용하여 시작된다. 그 다음, 올리베톨산 시클라아제는 테트라케티드 백본을 고리화하여 올리베톨산을 형성할 수 있다. OAC가 없으면, 테트라케티드는 자발적으로 고리화되어 칸나비노이드 생합성 경로에서 원하지 않는 부산물인 올리베톨을 형성할 수 있다. 이종 숙주에서 효소 성능을 개선하기 위해, 본 발명자들은 OAC에 효소 공학적 방법을 적용했다.
효소 공학은 폴리펩티드의 아미노산 서열에 변형을 일으켜 효소의 원하는 표현형을 개선하는 과정이다. 효소의 기능은 효소의 구조에 따라 달라지고, 효소의 구조는 부분적으로 1차 아미노산 서열에 따라 달라지기 때문에; 효소의 아미노산 서열의 변형은 원하는 표현형에 유익한 영향을 미칠 수 있다. 이 원리는 올리베톨산 시클라아제(OAC)에 적용되었으며, 유도 진화(directed evolution) 접근법을 사용하여 아미노산 서열에 변형이 이루어졌다. 이는 재조합 사카로마이세스 세레비시아에 균주에서 올리베톨산 생산이 개선된 아미노산 잔기들의 식별을 가능하게 했다. 그 다음, 유익한 돌연변이들을 함께 테스트하여 효소 성능을 개선하는 돌연변이들의 조합이 식별되었다.
야생형 OAC 서열과 비교하여 변형된 다수의 잔기들을 갖는 서열들이 본원에 기재되어 있다. 특정 돌연변이들은 사카로마이세스 세레비시아에에서 발현될 때 야생형 OAC보다 2배 이상 더 많은 올리베톨산을 생산한다. 조작된 OAC에서 나타나는 하나 이상의 효소 특성에 대한 개선에는 효소 활성의 증가, 효소 역학 및 회전율(turnover)의 개선, 증가된 기질 수준에 대한 더 높은 내성, 및 증가된 산물 수준에 대한 개선된 내성이 포함될 수 있다.
야생형 OAC 서열과 비교하여 아미노산 잔기의 변형은 보존적 변형이거나 비보존적 변형일 수 있다. 야생형 OAC에 대해, 잔기들을 변형시키는 데에는 삽입 또는 결실이 사용될 수 있다. 본원에 기재된 OAC에서 단백질은 야생형 OAC 서열의 다른 보고에서와 같이 102번 위치 대신 101번 위치에서 끝날 수 있다는 점에 유의한다. 본원에 기재된 구현예에서, X{#}로 표시된 잔기는 변형될 수 있으며, 이때 {#}은 본원에서 (서열 번호: 91)로 언급되는 야생형 OAC 서열의 아미노산 위치 내의 서열 위치를 나타낸다. 따라서, 서열 번호: 92는 아래에 개괄된 바와 같이 X{28}, X{31}, X{41}, X{43}, X{44}, X{68}, X{74}, X{84}, X{100}, 및 X{102}에서의 돌연변이 옵션을 포함한다:
서열 번호: 91은 야생형 OAC 단백질을 나타낸다:
MAVKHLIVLK FKDEITEAQK EEFFKTYVNL VNIIPAMKDV YWGKDVTQKN 50
KEEGYTHIVE VTFESVETIQ DYIIHPAHVG FGDVYRSFWE KLLIFDYTPR 100
KG 102
서열 번호: 92는 일반적인 변이체 OAC 단백질을 나타내며, 이때 X는 돌연변이된 잔기들에 대한 후보 위치들을 나타낸다(이때 X는 임의의 아미노산을 나타냄):
MAVKHLIVLK FKDEITEAQK EEFFKTYXNL XNIIPAMKDV XWXXDVTQKN 50
KEEGYTHIVE VTFESVEXIQ DYIXHPAHVG FGDXYRSFWE KLLIFDYTPX 100
KX 102
재료 및 방법:
유전자 조작:
벡터 VB40을 사용하여 OAC 및 변이체를 포함하는 본원에 개시된 효소 단백질들을 암호화하는 모든 발현 플라스미드들을 구축하였다.
OAC 변이체는 부위 포화 돌연변이유발 라이브러리 스크린에서 초기에 선택된 돌연변이들을 사용하여 조합 라이브러리에서 구축되었다. 플라스미드 VB40_OAC는 모든 라이브러리 구축에 템플릿으로 사용되었다.
정방향 축퇴 NNK 프라이머와 '백투백(back-to-back)' 역방향 비돌연변이유발 프라이머를 사용한 PCR 반응에 의해 각 아미노산 위치에서 부위 포화 돌연변이유발 반응을 수행하였다(도 3). 그 다음, PCR 산물을 시험관내 키나아제-리가아제-DpnI 반응을 통해 처리하고, 증폭을 위해 에스케리키아 콜라이(Escherichia coli) DH5알파 균주로 형질전환했다.
도 3은 부위 포화 돌연변이유발 프로토콜에 사용되는 PCR 프라이머를 도시한 것이다. 오른쪽 방향 화살표는 정방향 축퇴 NNK 프라이머를 나타내고, 기호 *는 돌연변이 위치를 나타내며, 왼쪽을 향하는 화살표는 정방향 프라이머의 반대 방향으로 '백투백'으로 설계된 역방향 프라이머를 나타낸다.
조합 라이브러리는 인하우스 프로토콜에 의해 구축되었다. 선택된 돌연변이들은 표적화 돌연변이유발 프라이머를 사용하여 생성된 돌연변이유발 올리고뉴클레오티드들의 배치의 중첩 확장 PCR을 통해 조합되었다(도 4). 조립된 조합 돌연변이 변이체들의 이중 가닥 DNA는 상보적인 중첩 서열들을 갖는 벡터 내로 클로닝되어 OAC 조합 변이체들의 풀이 생성되었다. 도 4는 조합 라이브러리 구축을 위한 돌연변이유발 올리고뉴클레오티드들의 중첩 확장 어셈블리를 도시한 것이다. 기호 x는 점 돌연변이를 나타낸다.
본원에 개시된 OAC 및 변이체 단백질들을 암호화하는 플라스미드들은 숙주 균주 HB1416을 사용하여 사카로마이세스 세레비시아에에서 형질전환 및 발현되었다. 모든 DNA는 Gietz 등의 형질전환 프로토콜(Gietz 2014)을 사용하여 배경 균주(background strain)들 내로 형질전환되었다.
균주 성장 및 배지:
균주들은 2% w/v 갈락토스, 2% w/v 라피노스, 200μg/l 제네티신, 및 200μg/L 암피실린(Sigma-Aldrich Canada)이 포함된, 황산암모늄이 없는 1.7g/L YNB, 1.92g/L URA 드롭아웃 아미노산 보충제, 1.5g/L 마그네슘 L-글루타메이트의 조성을 갖는 효모 합성 완전 배지에서 성장했다. 배양물을 30℃에서 4일(96시간) 동안 항온배양했다. 균주 HB1891 및 HB1892는 모든 스크리닝시 각각 야생형 대조군 및 음성 대조군으로 사용되었다.
변이체 스크리닝 조건:
각 변이체는 3회 반복하여 테스트되며, 각 반복물은 단일 콜로니들로부터 클론으로 얻은 것이었다. 모든 균주들은 96웰 딥웰 플레이트(deepwell plate)에서 96시간 동안 500μl의 배지에서 성장시켰다. 상기 96웰 딥웰 플레이트들을 30℃에서 항온배양하고, 950rpm에서 96시간 동안 진탕시켰다.
새로운 96웰 미량역가판에서 56% 아세토니트릴 270μl에 배양액 30μl를 첨가하여 대사산물 추출을 수행하였다. 상기 용액을 완전히 혼합한 다음, 3750rpm에서 10분 동안 원심분리했다. 가용성 층 200μl를 제거하고, 96웰 v-바닥 미량역가판에 보관하였다. 샘플들은 분석할 때까지 -20℃에서 보관하였다.
정량화 프로토콜:
Waters Acquity UPLC-TQD MS에서 HPLC-MS/MS를 사용하여 올리베톨산을 정량화하였다. 상기 크로마토그래피 및 MS 조건은 하기에 기재되어 있다.
HPLC 조건
컬럼: ACQUITY HSS C18 UPLC 50 × 1mm, 1.8μm 입자 크기(PN:186003529); 컬럼 온도: 45℃; 유속: 0.350mL/분; 용리액 A: 물 + 0.1% 포름산; 용리액 B: 아세토니트릴 + 0.1% 포름산; 구배는 표 1에 표시되어 있다.
ESI-MS 조건
하기 조건이 사용되었다: 모세관: 2.90(kV); 소스 온도: 150℃; 탈용매화 가스 온도: 250℃; 탈용매화 가스 흐름(질소): 500L/시간; 콘 가스 흐름(질소): 1L/시간; 검출 파라미터는 표 2에 표시되어 있다.
사용된 균주들은 표 3에 기재되어 있다.
표 4에 기재된 바와 같이, 하기 플라스미드들이 사용되었다.
하기 서열들은 본원에 기재되어 있다(표 5).
본원에 사용된 기본 균주들에 대한 변형은 아래 표 6에 요약되어 있다.
결과:
올리베톨산(OVLa)과 다운스트림 칸나비노이드의 개선된 생산을 입증하는 변이체의 식별
OAC 돌연변이 라이브러리는 Gal1p 프로모터에 의해 조절되는 플라스미드에 구축되었으며, 칸나비노이드 생산 경로의 다운스트림 효소들을 포함하는 올리베톨 생산 배경 균주(HB1416)에서 발현되었다. 개선된 활성을 갖는 OAC 돌연변이 히트들의 식별을 용이하게 하기 위해 야생형 OAC(HB1891) 및 mScarlet 형광 단백질(HB1892)을 발현하는 균주를 스크리닝시 대조군으로 사용하였다.
도 5는 조작된 OAC 균주들에 의한 올리베톨산 생산을 도시한 것이다. 각 칸나비노이드의 측정값들을 도 5에 나타내었다. 테스트된 돌연변이에는 침묵 돌연변이 G43G(GGG)가 존재했는데, 이는 플라스미드 구축 과정의 인공물로, 증가된 효소 성능과 관련이 없다.
표 7은 OAC 야생형 및 조작된 OAC 균주들에서 올리베톨, 올리베톨산, 및 다운스트림 칸나비노이드들의 생산을 나타낸 것이다.
표 8 OAC 변이체들에서 OVL에 대한 OVLa 또는 다운스트림 대사산물들(CBGa, CBDa, THCa)의 비율을 예시한 것이다.
표 9는 돌연변이 빈도 데이터의 요약을 제공한다.
숙주 세포에서의 사용
테트라하이드로칸나비놀(THC) 및 칸나비디올(CBD)과 같은 식물성 칸나비노이드는 의료 및 향정신성 목적으로 식물 소재에서 추출될 수 있다. 하지만, 식물 소재의 합성은 비용이 많이 들고, 대량으로 쉽게 확장될 수 없으며, 충분한 양의 식물성 칸나비노이드를 생산하려면 긴 성장 기간이 필요하다. 칸나비노이드를 생산할 수 있는 사카로마이세스 세레비시아에와 같은 발효 가능한 유기체는 이러한 화합물을 산업적 규모로 생산하는 데 있어 경제적인 경로를 제공할 것이다.
칸나비노이드 경로의 초기 단계는 유형 III PKS 올리베톨산 신타아제(OAS) 및 시클라아제 올리베톨산 시클라아제(OAC)에 의한 올리베톨산의 생성을 통해 진행된다. 이 반응은 헥사노일-CoA 스타터와 3개의 말로닐-CoA 단위들을 사용한다. 올리베톨산은 대부분의 고전적인 칸나비노이드들의 근간이 되는 것으로, 프레닐화되어 CBGA를 형성할 수 있으며, 이는 궁극적으로 옥시도시클라아제에 의해 CBDA 또는 THCA로 전환된다. 사카로마이세스 세레비시아에에서 올리베톨산의 생산은 OAS가 HTAL, PDAL 및 올리베톨과 같은 유의미한 부산물을 생성하기 때문에 어려운 작업이다. 이러한 부산물은 재조합 유기체에서 올리베톨산 시클라아제(OAC)를 도입함으로써 감소될 수 있지만, 이러한 효소를 사용해도 부산물은 반응에서 총 탄소의 최대 80%를 차지할 수 있다.
표 10은 기술된 경로들에서 칸나비노이드들의 제조를 위해 기술된 OAC 변이체들이 사용될 수 있는 숙주 세포 유기체들의 구체적인 예를 나열한 것이다.
식물성 칸나비노이드는 출원인의 동시 계류중인 국제 출원 번호 PCT/CA2020/050687(본원에 참조로 포함됨)에 기재된 바와 같이, 딕티오스텔리움 디스코이데움 폴리케티드 신타아제(DiPKS), 올리베톨산 시클라아제(OAC), 프레닐트랜스퍼라아제, 및/또는 이들의 돌연변이를 포함하는 숙주 세포에서 생산될 수 있습니다. 예를 들어, 폴리케티드 신타아제 코딩 서열, 올리베톨산 시클라아제 코딩 서열, 및 프레닐트랜스퍼라아제 코딩 서열로 형질전환된 숙주 세포가 제조될 수 있다. 폴리케티드 신타아제와 올리베톨산 시클라아제는 말로닐 CoA로부터 올리베톨산의 합성을 촉매한다. 올리베톨산 시클라아제는 야생형, 또는 본원에 기재된 임의의 기능적 돌연변이체들을 포함할 수 있다. 숙주 세포는 표 10에 나열된 것들 중에서 선택된 효모 세포, 박테리아 세포, 원생생물 세포, 또는 식물 세포를 포함할 수 있다.
출원인의 동시 계류중인 국제 출원 번호 PCT/CA2020/050687뿐만 아니라 본원에 기재된 방법들, 뉴클레오티드들, 및 발현 벡터들의 조합은 식물성 칸나비노이드, 폴리케티드와 같은 식물성 칸나비노이드 전구체를 생성하기 위해 함께 사용될 수 있다. 목적하는 산물에 따라, 칸나비노이드, 칸나비노이드 전구체, 또는 목적하는 중간체를 생산하도록 세포의 특성 선택 및 사용되는 방법이 선택될 수 있다.
식물성 칸나비노이드를 생산하는 방법은 식물성 칸나비노이드를 형성하기 위해 적합한 배양 조건 하에 숙주 세포를 배양하는 단계를 포함할 수 있으며, 상기 숙주 세포는 폴리케티드 신타아제(PKS) 효소를 암호화하는 폴리뉴클레오티드; 본원에 기재된 바와 같은 올리베톨산 시클라아제(OAC) 효소 돌연변이체를 암호화하는 폴리뉴클레오티드; 및 프레닐트랜스퍼라제(PT) 효소를 암호화하는 폴리뉴클레오티드를 포함하고; 선택적으로 다음을 포함한다: 아실-CoA 신타아제(Alk) 효소를 암호화하는 폴리뉴클레오티드; 지방 아실 CoA 활성화(CsAAE) 효소를 암호화하는 폴리뉴클레오티드; 및/또는 THCa 신타아제(OXC) 효소를 암호화하는 폴리뉴클레오티드.
폴리케티드 신타아제(PKS) 효소를 암호화하는 폴리뉴클레오티드; 본원에 기재된 바와 같은 올리베톨산 시클라아제(OAC) 효소 돌연변이체를 암호화하는 폴리뉴클레오티드; 및 프레닐트랜스퍼라아제(PT) 효소를 암호화하는 폴리뉴클레오티드를 포함하는 발현 벡터가 제조될 수 있다. 상기 발현 벡터는 선택적으로 아실-CoA 신타아제(Alk) 효소를 암호화하는 폴리뉴클레오티드; CsAAE1을 암호화하는 폴리뉴클레오티드; 및/또는 THCa 신타아제(OXC) 효소를 암호화하는 폴리뉴클레오티드;를 포함할 수 있다.
단지 예시 목적(Examples Only)
앞선 상세한 설명에서는, 설명을 목적으로 다양한 세부사항들을 기재하여 구현예들의 완전한 이해를 돕고자 하였다. 그러나, 이러한 특정 세부사항들은 필요조건이 아니라는 것이 당업자에게는 명백할 것이다.
본원에 기재된 구현예들은 단지 예시를 위한 것이다. 특정 구현예들에 대한 변경, 수정 및 변형이 당업자에 의해 이루어질 수 있다. 따라서, 청구범위의 범위는 본원에 기재된 특정 구현예들에 의해 제한되어서는 안 되며, 전체적으로 명세서와 일치하는 방식으로 해석되어야 한다.
본 발명이 이와 같이 설명되어 있는 바, 본 발명은 다양한 방식으로 변경될 수 있음이 명백할 것이다. 이러한 변형들은 본 발명의 개념과 범위에서 벗어나는 것으로 간주되어서는 안 되며, 당업자에게 자명한 이러한 모든 수정은 후술하는 청구범위의 범위 내에 포함되는 것으로 의도된다.
참고문헌
본 명세서에 언급한 모든 간행물들, 특허들, 및 특허 출원들은 본 발명이 속하는 기술 분야의 숙련가의 수준을 나타내는 것으로, 이들은 각각의 개별 간행물, 특허, 또는 특허 출원이 구체적이고 개별적으로 참조에 의해 본원에 포함되는 것으로 표시된 것과 동일한 정도로 본원에 참조로 포함된다.
특허 간행물
미국 특허 번호 7,361,482
미국 특허 번호 8,884,100 (Page et al.) Aromatic Prenyltransferase from Cannabis.
WO2018148848 (Mookerjee et al.) publication of PCT/CA2018/050189, METHOD AND CELL LINE FOR PRODUCTION OF PHYTOCANNABINOIDS AND PHYTOCANNABINOID ANALOGUES IN YEAST
WO2018148849 (Mookerjee et al.) publication of PCT/CA2018/050190, METHOD AND CELL LINE FOR PRODUCTION OF POLYKETIDES IN YEAST
비특허 문헌
Bai Flagfeldt, D., Siewers, V., Huang, L. and Nielsen, J. (2009) "Characterization of chromosomal integration sites for heterologous gene expression in Saccharomyces cerevisiae" Yeast, 26, 545-551.
Eisenberg, D., Schwarz, E., Komaromy, M., & Wall, R. (1984). "Analysis of membrane and surface protein sequences with the hydrophobic moment plot". Journal of Molecular Biology, 179(1), 125-142. https://doi.org/10.1016/0022-2836(84)90309-7.
Gagne, S. J., et al. (2012) "Identification of Olivetolic Acid Cyclase from Cannabis Sativa Reveals a Unique Catalytic Route to Plant Polyketides." Proceedings of the National Academy of Sciences, vol. 109, no. 31, 2012, pp. 12811-12816. doi:10.1073/pnas.1200330109.
Ghosh, R., A. Chhabra, P.A. Phatale, S.K. Samrat, J. Sharma, A. Gosain, D. Mohanty, S. Saran and R.S. Gokhale (2008) "Dissecting the Functional Role of Polyketide Synthases in Dictyostelium discoideum biosynthesis of the differentiation regulating factor 4-methyl-5-pentylbenzene-1,3-diol" Journal of Biological Chemistry, 283(17), 11348-11354.
Gietz, R. D. and Schiestl, R. H., (2007) "High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method." Nat. Protoc. 2, 31-34.
Gietz R.D. (2014) Yeast Transformation by the LiAc/SS Carrier DNA/PEG Method (pp 1-12). In: Smith J., Burke D. (eds) Yeast Genetics. Methods in Molecular Biology (Methods and Protocols), vol 1205. Humana Press, New York, NY. https: //doi.org/10.1007/978-1-4939-1363-3_1.
Jensen, N. B., Strucko, T., Kildegaard, K. R., David, F., et al., (2014). EasyClone: method for iterative chromosomal integration of multiple genes in Saccharomyces cerevisiae. FEMS Yeast Research, Volume 14, Issue 2, pages 238-248; https ://doi.org/10.1111/1567 -1364.12118.
Kim, J.-M., Song, H.-Y., Choi, H.-J., So, K.-K., Kim, D.-H., Chae, K.-S., ... Jahng, K.-Y. (2015). "Characterization of NpgA, a 4'-phosphopantetheinyl transferase of Aspergillus nidulans, and evidence of its involvement in fungal growth and formation of conidia and cleistothecia for development." Journal of Microbiology, 53(1), 21-31 https: //doi.org/10.1007/s12275-015-4657-8.
Kuzuyama et al. (2005) Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products, Nature, volume 435, pages 983-987; doi: 10.1038/nature03668.
Liu, J., Zhang, W., Du, G., Chen, J., & Zhou, J. (2013). "Overproduction of geraniol by enhanced precursor supply in Saccharomyces cerevisiae." Journal of Biotechnology, 168(4), 446-451. https: //doi.org/10.1016/J.JBIOTEC.2013.10.017.
Luo, X., Reiter, M., d'Espaux, L., Wong, J., Denby, C., Lechner, A., Zhang, Y., Grzybowski, A., Harth, S., Lin, W., Lee, H., Yu, C., Shin, J., Deng, K., Benites, V., Wang, G., Baidoo, E., Chen, Y., Dev, I., Petzold, C. and Keasling, J. (2019). "Complete biosynthesis of cannabinoids and their unnatural analogues in yeast." Nature, 567(7746), pp.123-126.
Oswald, Marilyne; Marc Fischer, Nicole Dirninger, Francis Karst, (2007) "Monoterpenoid biosynthesis in Saccharomyces cerevisiae." FEMS Yeast Research, 7(3), 413-421. https: //doi.org/10.1111/j.1567-1364.2006.00172.x
Peng, B., Nielsen, L. K., Kampranis, S. C., & Vickers, C. E. (2018). Engineered protein degradation of farnesyl pyrophosphate synthase is an effective regulatory mechanism to increase monoterpene production in Saccharomyces cerevisiae. Metabolic Engineering, 47, 83-93. https ://doi.org/10.1016/J.YMBEN.2018.02.005.
Ro, D.-K., Paradise, E. M., Ouellet, M., Fisher, K. J., Newman, K. L., Ndungu, J. M., Keasling, J. D. (2006). Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature, 440(7086), 940-943. JOUR. https: //doi.org/10.1038/nature04640.
Ryan, O. W., Poddar, S., & Cate, J. H. D. (2016). CRISPR-Cas9 Genome Engineering in Saccharomyces cerevisiae Cells. Cold Spring Harbor Protocols, 2016(6), pdb.prot086827. https: //doi.org/10.1101/pdb.prot086827.
Saeki, H., Hara, R., Takahashi, H., Iijima, M., Munakata, R., Kenmoku, H., ... Taura, F. (2018). An Aromatic Farnesyltransferase Functions in Biosynthesis of the Anti-HIV Meroterpenoid Daurichromenic Acid. Plant Physiology, 178(2), 535-551; https: //doi.org/10.1104/PP.18.00655.
Shi, S., Chen, Y., Siewers, V., & Nielsen, J. (2014). "Improving Production of Malonyl Coenzyme A-Derived Metabolites by Abolishing Snf1-Dependent Regulation of Acc1." mBio, 5(3), e01130-14. https: //doi.org/10.1128/mBio.01130-14.
Shiba, Y., Paradise, E. M., Kirby, J., Ro, D.-K., & Keasling, J. D. (2007). "Engineering of the pyruvate dehydrogenase bypass in Saccharomyces cerevisiae for high-level production of isoprenoids." Metabolic Engineering, 9(2), 160-168. https: //doi.org/10.1016/J.YMBEN.2006.10.005.
Sirikantaramas, S., Taura, F., Tanaka, Y., Ishikawa, Y., Morimoto, S., & Shoyama, Y. (2005). "Tetrahydrocannabinolic acid synthase, the enzyme controlling marijuana psychoactivity, is secreted into the storage cavity of the glandular trichomes". Plant and Cell Physiology, 46(9), 1578-1582.
Stout, J. M., Boubakir, Z., Ambrose, S. J., Purves, R. W., & Page, J. E. (2012). The hexanoyl-CoA precursor for cannabinoid biosynthesis is formed by an acyl-activating enzyme in Cannabis sativa trichomes. The Plant Journal, 71(3), 353-365.
Taura, Futoshi, et al. (2009) "Characterization of olivetol synthase, a polyketide synthase putatively involved in cannabinoid biosynthetic pathway." FEBS letters, 583.12 (2009): 2061-2066.
Varshavsky, A. (2011). The N-end rule pathway and regulation by proteolysis. Protein Science 20(8):1285-1476. https: //doi.org/10.1002/pro.666.
SEQUENCE LISTING <110> Hyasynth Biologicals Inc. <120> OLIVETOLIC ACID CYCLASE VARIANTS WITH IMPROVED ACTIVITY FOR USE IN PRODUCTION OF PHYTOCANNABINOIDS <130> PAT 109718W-90 <150> US 16/953638 <151> 2020-11-20 <160> 93 <170> PatentIn version 3.5 <210> 1 <211> 6114 <212> DNA <213> Artificial Sequence <220> <223> mScarlet nucleotide sequence <400> 1 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggtgtctaaa ggtgaagccg tcatcaaaga attcatgaga ttcaaggttc 2700 acatggaagg ttctatgaat ggtcacgaat tcgaaattga aggtgaaggt gagggtagac 2760 catatgaagg tactcaaact gctaagttga aggttacaaa aggtggtcca ttgccattct 2820 cttgggatat tttgtctcca caattcatgt acggttctag agcttttaca aaacacccag 2880 ctgatatccc agattactac aagcaatcat ttccagaggg tttcaagtgg gaaagagtta 2940 tgaattttga agatggtggt gccgttactg ttactcaaga tacttctttg gaagatggca 3000 ccttgatcta caaggttaag ttgagaggta ctaatttccc accagatggt ccagttatgc 3060 aaaaaaagac tatgggttgg gaagctagta ctgaaagatt atatccagag gatggtgttt 3120 tgaagggtga tattaagatg gccttgagat tgaaagacgg tggtagatat ttggctgatt 3180 tcaagactac ttacaaggcc aaaaagccag ttcaaatgcc aggtgcttat aacgttgata 3240 gaaagttgga tatcacctct cacaacgaag attacaccgt tgttgaacag tacgaaagat 3300 ctgaaggtag acattctact ggtggtatgg atgagttgta caagtaactc gagcatgcat 3360 ctagagggcc gcatcatgta attagttatg tcacgcttac attcacgccc tccccccaca 3420 tccgctctaa ccgaaaagga aggagttaga caacctgaag tctaggtccc tatttatttt 3480 tttatagtta tgttagtatt aagaacgtta tttatatttc aaatttttct tttttttctg 3540 tacagacgcg tgtacgcatg taacattata ctgaaaacct tgcttgagaa ggttttggga 3600 cgctcgaagg ctttaatttg cggccctgca ttaatgaatc ggccaacgcg cggggagagg 3660 cggtttgcgt attgggcgct cttccgcttc ctcgctcact gactcgctgc gctcggtcgt 3720 tcggctgcgg cgagcggtat cagctcactc aaaggcggta atacggttat ccacagaatc 3780 aggggataac gcaggaaaga acatgtgagc aaaaggccag caaaagccca ggaaccgtaa 3840 aaaggccgcg ttgctggcgt ttttccatag gctccgcccc cctgacgagc atcacaaaaa 3900 tcgacgctca agtcagaggt ggcgaaaccc gacaggacta taaagatacc aggcgtttcc 3960 ccctggaagc tccctcgtgc gctctcctgt tccgaccctg ccgcttaccg gatacctgtc 4020 cgcctttctc ccttcgggaa gcgtggcgct ttctcatagc tcacgctgta ggtatctcag 4080 ttcggtgtag gtcgttcgct ccaagctggg ctgtgtgcac gaaccccccg ttcagcccga 4140 ccgctgcgcc ttatccggta actatcgtct tgagtccaac ccggtaagac acgacttatc 4200 gccactggca gcagccactg gtaacaggat tagcagagcg aggtatgtag gcggtgctac 4260 agagttcttg aagtggtggc ctaactacgg ctacactaga agaacagtat ttggtatctg 4320 cgctctgctg aagccagtta ccttcggaaa aagagttggt agctcttgat ccggcaaaca 4380 aaccaccgct ggtagcggtg gtttttttgt ttgcaagcag cagattacgc gcagaaaaaa 4440 aggatctcaa gaagatcctt tgatcttttc tacggggtct gacgctcagt ggaacgaaaa 4500 ctcacgttaa gggattttgg tcatgagatt atcaaaaagg atcttcacct agatcctttt 4560 aaattaaaaa tgaagtttta aatcaatcta aagtatatat gagtaaactt ggtctgacag 4620 ttaccaatgc ttaatcagtg aggcacctat ctcagcgatc tgtctatttc gttcatccat 4680 agttgcctga ctccccgtcg tgtagataac tacgatacgg gagcgcttac catctggccc 4740 cagtgctgca atgataccgc gagacccacg ctcaccggct ccagatttat cagcaataaa 4800 ccagccagcc ggaagggccg agcgcagaag tggtcctgca actttatccg cctccattca 4860 gtctattaat tgttgccggg aagctagagt aagtagttcg ccagttaata gtttgcgcaa 4920 cgttgttggc attgctacag gcatcgtggt gtcactctcg tcgtttggta tggcttcatt 4980 cagctccggt tcccaacgat caaggcgagt tacatgatcc cccatgttgt gcaaaaaagc 5040 ggttagctcc ttcggtcctc cgatcgttgt cagaagtaag ttggccgcag tgttatcact 5100 catggttatg gcagcactgc ataattctct tactgtcatg ccatccgtaa gatgcttttc 5160 tgtgactggt gagtactcaa ccaagtcatt ctgagaatag tgtatgcggc gaccgagttg 5220 ctcttgcccg gcgtcaatac gggataatag tgtatcacat agcagaactt taaaagtgct 5280 catcattgga aaacgttctt cggggcgaaa actctcaagg atcttaccgc tgttgagatc 5340 cagttcgatg taacccactc gtgcacccaa ctgatcttca gcatctttta ctttcaccag 5400 cgtttctggg tgagcaaaaa caggaaggca aaatgccgca aaaaagggaa taagggcgac 5460 acggaaatgt tgaatactca tactcttcct ttttcaatgg gtaataactg atataattaa 5520 attgaagctc taatttgtga gtttagtata catgcattta cttataatac agttttttag 5580 ttttgctggc cgcatcttct caaatatgct tcccagcctg cttttctgta acgttcaccc 5640 tctaccttag catcccttcc ctttgcaaat agtcctcttc caacaataat aatgtcagat 5700 cctgtagaga ccacatcatc cacggttcta tactgttgac ccaatgcgtc tcccttgtca 5760 tctaaaccca caccgggtgt cataatcaac caatcgtaac cttcatctct tccacccatg 5820 tctctttgag caataaagcc gataacaaaa tctttgtcgc tcttcgcaat gtcaacagta 5880 cccttagtat attctccagt agatagggag cccttgcatg acaattctgc taacatcaaa 5940 aggcctctag gttcctttgt tacttcttct gccgcctgct tcaaaccgct aacaatacct 6000 gggcccacca caccgtgtgc attcgtaatg tctgcccatt ctgctattct gtatacaccc 6060 gcagagtact gcaatttgac tgtattacca atgtcagcaa attttctgtc ttcg 6114 <210> 2 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC wild type nucleotide sequence <400> 2 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggt taacatcatt cctgctatga 2760 aggacgtcta ctggggtaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaaa ctattcaaga ctacatcatt cacccagctc 2880 acgtcggttt cggtgatgtt tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gggctaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 3 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/T68L/I74E/V84R/R100M/G102R <400> 3 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcac gtgggggaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcgag cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaatgaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 4 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R <400> 4 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggt taacatcatt cctgctatga 2760 aggacgtctc ctggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gggctaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 5 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41S/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102 R <400> 5 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggg gaacatcatt cctgctatga 2760 aggacgtctc ctggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 6 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/T68L/I74G/V84R/R100E <400> 6 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcac gtgggggaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gggctaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 7 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/K44V/T68L/I74D/V84R/R100M/G102R <400> 7 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcgac cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaatgaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 8 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/T68L/I74D/V84R/G102R <400> 8 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcac gtgggggaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcgac cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 9 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102R <400> 9 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 10 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-Y41T/G43SILENT(=GGG)/T68R/I74R/V84R/R100M/G102STOP <400> 10 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggt taacatcatt cctgctatga 2760 aggacgtcac gtgggggaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaatgaa gtaataactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 11 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/R100E/G102R <400> 11 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcgt gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 12 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/K44V/T68R/I74G/V84R/G102STOP <400> 12 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gtaataactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 13 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102STOP <400> 13 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcgt gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gtaataactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 14 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74E/V84R/R100E <400> 14 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggg gaacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcgag cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gggctaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 15 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41S/G43SILENT(=GGG)/T68R/I74R/V84R/R100M/G102STOP <400> 15 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtctc ctgggggaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaatgaa gtaataactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 16 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-Y41T/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/G102R <400> 16 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggt taacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 17 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100E/G102R <400> 17 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 18 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R <400> 18 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggg gaacatcatt cctgctatga 2760 aggacgtctc ctggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gggctaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 19 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/G43SILENT(=GGG)/K44V/I74D/V84R/R100E/G102R(=CGC) <400> 19 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcta ctggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaaa ctattcaaga ctacatcgac cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gcgctaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 20 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/G102R <400> 20 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcgt gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 21 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-Y41T/G43SILENT(=GGG)/T68L/I74G/V84R/R100M/G102R <400> 21 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggt taacatcatt cctgctatga 2760 aggacgtcac gtgggggaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaatgaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 22 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100E/G102 R <400> 22 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggg gaacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 23 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V31G/Y41S/G43SILENT(=GGG)/K44V/T68R/V84R/R100E <400> 23 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggg gaacatcatt cctgctatga 2760 aggacgtctc ctggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcatt cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gggctaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 24 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/T68L/I74D/R100E/G102STOP <400> 24 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcgt gtgggggaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcgac cacccagctc 2880 acgtcggttt cggtgatgtt tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gtaataactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 25 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/T68R/I74G/V84R/R100M/G102R <400> 25 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcgt gtgggggaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaatgaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 26 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V31G/G43SILENT(=GGG)/I74G/V84R/R100E <400> 26 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggg gaacatcatt cctgctatga 2760 aggacgtcta ctgggggaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaaa ctattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gggctaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 27 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100M/G102R <400> 27 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtctc ctggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaatgaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 28 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R <400> 28 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggg gaacatcatt cctgctatga 2760 aggacgtcgt gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gggctaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 29 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/R100M/G102R <400> 29 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcgt gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaatgaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 30 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/V31G/G43SILENT(=GGG)/T68L/I74R/V84R/R100E/G102R <400> 30 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggg gaacatcatt cctgctatga 2760 aggacgtcta ctgggggaag gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 31 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V31G/Y41V/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102STOP <400> 31 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggg gaacatcatt cctgctatga 2760 aggacgtcgt gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gtaataactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 32 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74D/V84R/G102R <400> 32 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggg gaacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcgac cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 33 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74D/V84R/R100E/G102R <400> 33 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggg gaacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcgac cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 34 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41S/G43SILENT(=GGG)/K44V/T68R/I74G/V84R/R100M/G102R <400> 34 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtctc ctggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcggg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaatgaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 35 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/K44V/I74R/R100E/G102STOP <400> 35 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcgt gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaaa ctattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatgtt tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gtaataactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 36 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/I74E/V84R/R100M/G102R <400> 36 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggg gaacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaaa ctattcaaga ctacatcgag cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaatgaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 37 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V28A/G43SILENT(=GGG)/K44V/T68R/I74E/V84R/R100E/G102STOP <400> 37 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg cgaacttggt taacatcatt cctgctatga 2760 aggacgtcta ctggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac ggattcaaga ctacatcgag cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccagagaa gtaataactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 38 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-V31G/Y41T/G43SILENT(=GGG)/K44V/T68L/I74D/V84R/G102R <400> 38 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggg gaacatcatt cctgctatga 2760 aggacgtcac gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcgac cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 39 <211> 5724 <212> DNA <213> Artificial Sequence <220> <223> OAC-Y41V/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/G102R <400> 39 aagagtaaaa aattgtactt ggcggataat gcctttagcg gcttaactgt gccctccatg 60 gaaaaatcag tcaagatatc cacatgtgtt tttagtaaac aaattttggg acctaatgct 120 tcaactaact ccagtaattc cttggtggta cgaacatcca atgaagcaca caagtttgtt 180 tgcttttcgt gcatgatatt aaatagcttg gcagcaacag gactaggatg agtagcagca 240 cgttccttat atgtagcttt cgacatgatt tatcttcgtt tcctgcaggt ttttgttctg 300 tgcagttggg ttaagaatac tgggcaattt catgtttctt caacactaca tatgcgtata 360 tataccaatc taagtctgtg ctccttcctt cgttcttcct tctgttcgga gattaccgaa 420 tcaaaaaaat ttcaaagaaa ccgaaatcaa aaaaaagaat aaaaaaaaaa tgatgaattg 480 aattgaaaag ctagcttatc gatgataagc tgtcaaagat gagaattaat tccacggact 540 atagactata ctagatactc cgtctactgt acgatacact tccgctcagg tccttgtcct 600 ttaacgaggc cttaccactc ttttgttact ctattgatcc agctcagcaa aggcagtgtg 660 atctaagatt ctatcttcgc gatgtagtaa aactagctag accgagaaag agactagaaa 720 tgcaaaaggc acttctacaa tggctgccat cattattatc cgatgtgacg ctgcagcttc 780 tcaatgatat tcgaatacgc tttgaggaga tacagcctaa tatccgacaa actgttttac 840 agatttacga tcgtacttgt tacccatcat tgaattttga acatccgaac ctgggagttt 900 tccctgaaac agatagtata tttgaacctg tataataata tatagtctag cgctttacgg 960 aagacaatgt atgtatttcg gttcctggag aaactattgc atctattgca taggtaatct 1020 tgcacgtcgc atccccggtt cattttctgc gtttccatct tgcacttcaa tagcatatct 1080 ttgttcgctt gcctgtaact tacacgcgcc tcgtatcttt taatgatgga ataatttggg 1140 aatttactct gtgtttattt atttttatgt tttgtatttg gattttagaa agtaaataaa 1200 gaaggtagaa gagttacgga atgaagaaaa aaaaataaac aaaggtttaa aaaatttcaa 1260 caaaaagcgt actttacata tatatttatt agacaagaaa agcagattaa atagatatac 1320 attcgattaa cgataagtaa aatgtaaaat cacaggattt tcgtgtgtgg tcttctacac 1380 agacaagatg aaacaattcg gcattaatac ctgagagcag gaagagcaag ataaaaggta 1440 gtatttgttg gcgatccccc tagagtcttt tacatcttcg gaaaacaaaa actatttttt 1500 ctttaatttc tttttttact ttctattttt aatttatata tttatattaa aaaatttaaa 1560 ttataattat ttttatagca cgtgatgaaa aggaccggga agctccaccc cggttgataa 1620 tcagaaaagc cccaaaaaca ggaagattgt ataagcaaat atttaaattg taaacgttaa 1680 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta acgaatagcc 1740 cgaaatcggc aaaatccctt ataaatcaaa agaatagacc gagatagggt tgagtgttgt 1800 tccagtttcc aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 1860 aagggtctat cagggcgatg gcccactacg tgaaccatca ccctaatcaa gttttttggg 1920 gtcgaggtgc cgtaaagcag taaatcggaa gggtaaacgg atgcccccat ttagagcttg 1980 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggggc 2040 tagggcggtg ggaagtgtag gggtcacgct gggcgtaacc accacacccg ccgcgcttaa 2100 tggggcgcta cagggcgcgt ggggatgatc cactagtacg gattagaagc cgccgagcgg 2160 gtgacagccc tccgaaggaa gactctcctc cgtgcgtcct cgtcttcacc ggtcgcgttc 2220 ctgaaacgca gatgtgcctc gcgccgcact gctccgaaca ataaagattc tacaatacta 2280 gcttttatgg ttatgaagag gaaaaattgg cagtaacctg gccccacaaa ccttcaaatg 2340 aacgaatcaa attaacaacc ataggatgat aatgcgatta gttttttagc cttatttctg 2400 gggtaattaa tcagcgaagc gatgattttt gatctattaa cagatatata aatgcaaaaa 2460 ctgcataacc actttaacta atactttcaa cattttcggt ttgtattact tcttattcaa 2520 atgtaataaa agtatcaaca aaaaattgtt aatatacctc tatactttaa cgtcaaggag 2580 aaaaaacccc ggatcggact actagcagct gtaatacgac tcactatagg gaatattaag 2640 cttaaacaat ggccgtcaag cacttgatcg tcttaaagtt taaggacgag atcactgaag 2700 cccaaaagga agaattcttc aaaacttacg ttaacttggt taacatcatt cctgctatga 2760 aggacgtcgt gtggggggtg gatgtcactc aaaaaaacaa ggaagaaggt tatacccaca 2820 tcgttgaagt caccttcgaa tctgttgaac tgattcaaga ctacatcagg cacccagctc 2880 acgtcggttt cggtgatagg tacagatctt tctgggaaaa attgttgatc ttcgactaca 2940 ccccaagaaa gcggtaactc gagcatgcat ctagagggcc gcatcatgta attagttatg 3000 tcacgcttac attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga 3060 caacctgaag tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta 3120 tttatatttc aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata 3180 ctgaaaacct tgcttgagaa ggttttggga cgctcgaagg ctttaatttg cggccctgca 3240 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 3300 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 3360 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 3420 aaaaggccag caaaagccca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 3480 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 3540 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 3600 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 3660 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 3720 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 3780 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 3840 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 3900 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 3960 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 4020 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 4080 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 4140 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 4200 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 4260 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 4320 tacgatacgg gagcgcttac catctggccc cagtgctgca atgataccgc gagacccacg 4380 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 4440 tggtcctgca actttatccg cctccattca gtctattaat tgttgccggg aagctagagt 4500 aagtagttcg ccagttaata gtttgcgcaa cgttgttggc attgctacag gcatcgtggt 4560 gtcactctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 4620 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 4680 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 4740 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 4800 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatag 4860 tgtatcacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 4920 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 4980 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 5040 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 5100 ttttcaatgg gtaataactg atataattaa attgaagctc taatttgtga gtttagtata 5160 catgcattta cttataatac agttttttag ttttgctggc cgcatcttct caaatatgct 5220 tcccagcctg cttttctgta acgttcaccc tctaccttag catcccttcc ctttgcaaat 5280 agtcctcttc caacaataat aatgtcagat cctgtagaga ccacatcatc cacggttcta 5340 tactgttgac ccaatgcgtc tcccttgtca tctaaaccca caccgggtgt cataatcaac 5400 caatcgtaac cttcatctct tccacccatg tctctttgag caataaagcc gataacaaaa 5460 tctttgtcgc tcttcgcaat gtcaacagta cccttagtat attctccagt agatagggag 5520 cccttgcatg acaattctgc taacatcaaa aggcctctag gttcctttgt tacttcttct 5580 gccgcctgct tcaaaccgct aacaatacct gggcccacca caccgtgtgc attcgtaatg 5640 tctgcccatt ctgctattct gtatacaccc gcagagtact gcaatttgac tgtattacca 5700 atgtcagcaa attttctgtc ttcg 5724 <210> 40 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/T68L/I74E/V84R/R100M/G102R <400> 40 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Glu His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Met Lys Arg 100 <210> 41 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R <400> 41 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Ser Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys Gly 100 <210> 42 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41S/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102 R <400> 42 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Ser Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Arg 100 <210> 43 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/T68L/I74G/V84R/R100E <400> 43 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Gly 100 <210> 44 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/K44V/T68L/I74D/V84R/R100M/G102R <400> 44 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Asp His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Met Lys Arg 100 <210> 45 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/T68L/I74D/V84R/G102R <400> 45 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Asp His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys Arg 100 <210> 46 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102R <400> 46 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Arg 100 <210> 47 <211> 101 <212> PRT <213> Artificial Sequence <220> <223> OAC-Y41T/G43SILENT(=GGG)/T68R/I74R/V84R/R100M/G102STOP <400> 47 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Met Lys 100 <210> 48 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/R100E/G102R <400> 48 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Val Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Arg 100 <210> 49 <211> 101 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/K44V/T68R/I74G/V84R/G102STOP <400> 49 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys 100 <210> 50 <211> 101 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102STOP <400> 50 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Val Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys 100 <210> 51 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74E/V84R/R100E <400> 51 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Glu His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Gly 100 <210> 52 <211> 101 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41S/G43SILENT(=GGG)/T68R/I74R/V84R/R100M/G102STOP <400> 52 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Ser Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Met Lys 100 <210> 53 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-Y41T/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/G102R <400> 53 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys Arg 100 <210> 54 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41T/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100E/G102R <400> 54 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Arg 100 <210> 55 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R <400> 55 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Ser Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys Gly 100 <210> 56 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/G43SILENT(=GGG)/K44V/I74D/V84R/R100E/G102R(=CGC) <400> 56 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Tyr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Thr Ile Gln Asp Tyr Ile Asp His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Arg 100 <210> 57 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/G102R <400> 57 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Val Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys Arg 100 <210> 58 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-Y41T/G43SILENT(=GGG)/T68L/I74G/V84R/R100M/G102R <400> 58 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Met Lys Arg 100 <210> 59 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100E/G102 R <400> 59 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Arg 100 <210> 60 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V31G/Y41S/G43SILENT(=GGG)/K44V/T68R/V84R/R100E <400> 60 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Ser Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Ile His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Gly 100 <210> 61 <211> 101 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/T68L/I74D/R100E/G102STOP <400> 61 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Val Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Asp His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Val Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys 100 <210> 62 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/T68R/I74G/V84R/R100M/G102R <400> 62 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Val Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Met Lys Arg 100 <210> 63 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V31G/G43SILENT(=GGG)/I74G/V84R/R100E <400> 63 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Tyr Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Thr Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Gly 100 <210> 64 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100M/G102R <400> 64 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Ser Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Met Lys Arg 100 <210> 65 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84 <400> 65 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Val Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys Gly 100 <210> 66 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/R100M/G102R <400> 66 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Val Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Met Lys Arg 100 <210> 67 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/V31G/G43SILENT(=GGG)/T68L/I74R/V84R/R100E/G102R <400> 67 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Tyr Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Arg 100 <210> 68 <211> 101 <212> PRT <213> Artificial Sequence <220> <223> OAC-V31G/Y41V/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102STOP <400> 68 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Val Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys 100 <210> 69 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74D/V84R/G102R <400> 69 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Asp His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys Arg 100 <210> 70 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74D/V84R/R100E/G102R <400> 70 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Asp His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys Arg 100 <210> 71 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41S/G43SILENT(=GGG)/K44V/T68R/I74G/V84R/R100M/G102R <400> 71 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Ser Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Gly His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Met Lys Arg 100 <210> 72 <211> 101 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/Y41V/G43SILENT(=GGG)/K44V/I74R/R100E/G102STOP <400> 72 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Val Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Thr Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Val Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys 100 <210> 73 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/I74E/V84R/R100M/G102R <400> 73 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Thr Ile Gln Asp Tyr Ile Glu His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Met Lys Arg 100 <210> 74 <211> 101 <212> PRT <213> Artificial Sequence <220> <223> OAC-V28A/G43SILENT(=GGG)/K44V/T68R/I74E/V84R/R100E/G102STOP <400> 74 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Ala Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Tyr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Arg Ile Gln Asp Tyr Ile Glu His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Glu Lys 100 <210> 75 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-V31G/Y41T/G43SILENT(=GGG)/K44V/T68L/I74D/V84R/G102R <400> 75 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Gly Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Thr Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Asp His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys Arg 100 <210> 76 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OAC-Y41V/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/G102R <400> 76 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Val Trp Gly Val Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Leu Ile Gln Asp Tyr Ile Arg His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Arg Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys Arg 100 <210> 77 <211> 3564 <212> DNA <213> Artificial Sequence <220> <223> NpgA DNA <400> 77 tcaatcaaag caacccacaa atcctaggct gaatcatgat atcgatggaa gcaatcaaca 60 attttatcaa gaccgcacca aagcacgact atctgacagg cggagttcat cattctggta 120 atgtagacgt gttacaatta agcggcaata aagaagatgg tagtttagta tggaaccata 180 cttttgttga tgtagacaac aatgtggtag ctaagtttga agacgctctc gaaaaacttg 240 aaagtttgca ccggcgctca tcctcatcca caggcaatga agaacacgct aacgtttaac 300 cgaggggagt cacttcataa tgatgtgaga aataagtgaa tattgtaata attgttggga 360 ctccattgtc aacaaaagct ataatgtagg tatacagtat atactagaag ttctcctcga 420 ggatcttgga atccacaaaa gggagtcgat aaatctatat aataaaaatt actttatctt 480 ctttcgtttt atacgttgtc gtttattatc ctattacgtt atcaatcttc gcatttcagc 540 tttcattaga tttgatgact gtttctcaaa ctttatgtca ttttcttaca ccgcataaac 600 aacaaataat cataaaaatt ttagaactag acataaagca acaggcgcgt tggactttta 660 attttcgagg accgcgaatc cttacatcac acccaatccc ccacaagtga tcccccacac 720 accatagctt caaaatgttt ctactccttt tttactcttc cagattttct cggactccgc 780 gcatcgccgt accacttcaa aacacccaag cacagcatac taaatttccc ctctttcttc 840 ctctagggtg tcgttaatta cccgtactaa aggtttggaa aagaaaaaag agaccgcctc 900 gtttcttttt cttcgtcgaa aaaggcaata aaaattttta tcacgtttct ttttcttgaa 960 aatttttttt tttgattttt ttctctttcg atgacctccc attgatattt aagttaataa 1020 acggtcttca atttctcaag tttcagtttc atttttcttg ttctattaca acttttttta 1080 cttcttgctc attagaaaga aagcatagca atctaatcta agttttaatc tagaaaattt 1140 attataaaag gaagagaaat aattaaacaa tggttcaaga tacctcttct gcttctacct 1200 ctccaatttt gactagatgg tacattgata ccagaccatt gactgcttct actgctgctt 1260 tgccattatt ggaaacttta caaccagccg atcaaatctc cgttcaaaag tactatcact 1320 tgaaggacaa gcacatgtct ttggcttcta acttgttgaa gtacttgttc gttcacagaa 1380 actgcagaat tccatggtcc tctatcgtta tttctagaac tccagatcca catagaaggc 1440 catgttatat tccaccatct ggttctcaag aggattcttt taaagatggt tacaccggta 1500 tcaacgtcga gtttaatgtt tctcatcaag cctccatggt tgctattgct ggtactgctt 1560 ttactccaaa ttctggtggt gattctaagt tgaaaccaga agttggtatc gatattacct 1620 gcgtcaacga aagacaaggt agaaatggtg aagaaaggtc cttggaatct ttgagacagt 1680 acatcgatat cttctccgaa gttttctcta ctgctgaaat ggccaacatt agaagattgg 1740 atggtgtctc ttcttcctca ttgtctgctg atagattggt tgattatggc tacaggttgt 1800 tctatactta ctgggctttg aaagaagcct acattaagat gactggtgaa gccttgttgg 1860 ctccatggtt gagagaattg gaattctcta atgttgttgc tccagctgct gttgctgaat 1920 ctggtgattc tgctggtgat tttggtgaac catatactgg tgttagaacc accttgtaca 1980 agaacttggt tgaagatgtt agaattgaag ttgctgcttt gggtggtgat tacttgtttg 2040 ctactgctgc tagaggtggt ggtattggtg cttcttctag accaggtggt ggtccagatg 2100 gttctggtat tagatctcaa gatccttgga ggccattcaa gaagttggat attgaaaggg 2160 atattcaacc atgtgctact ggtgtatgta actgcttgtc ttaaagacat aaaactgaaa 2220 caacaccaat taataataga ctttacagaa gacgggagac actagcacac aactttacca 2280 ggcaaggtat ttgacgctag catgtgtcca attcagtgtc atttatgatt ttttgtagta 2340 ggatataaat atatacagcg ctccaaatag tgcggttgcc ccaaaaacac cacggaacct 2400 catctgttct cgtactttgt tgtgacaaag tagctcactg ccttattatc acattttcat 2460 tatgcaacgc ttcggaaaat acgatgttga aaatgcctct agagatgaaa aacaatcgta 2520 aaagggtcct gcgtaattga aacatttgat cagtatgcag tggcacagaa acaaccagga 2580 atactatagt cataggcaat acaaggtata tattggctat gcagacccct ccagaaagta 2640 ccgacgtcaa gttagataca cttaacgaac ctagtgcaca tttaattgag aaaaatgtgg 2700 ctcttcctaa ggacatattc cgttcgtact tgagttattg gatctatgaa atcgctcgct 2760 atacaccagt catgattttg tccttaaata acatactcat cactaaacat tcttaacaat 2820 cagaaaatgc aaccgataaa acattataaa tcttcgcggt tatctggcat tgttattaac 2880 caaaaaaatg ccggcctatt acaagctact gttcaataaa tattgttgta atgaagacgg 2940 tccaactgta caaatacagc aaactgtcat atataaggtg tcttatgtga cagcacttgc 3000 gttattgtca gccggagtat gtctttgtcg cattctgggc tttttacttt ctgctcagaa 3060 ggaagtacga acaagaaaaa aaaatcacca atgcttccct tttcagtatt agtttcatat 3120 ttgtttacgt tcaaactcgt cgtttgcgcg ataacctcta aaaaagtcag ttacgtaact 3180 atatcaatca gagaatgcaa aaagcactat cataaaaatg tctctagggg atgtgagaca 3240 tgtcaattat aagaagtgat ggtgtcatag tatatatatc ataaatgatt atcaaagttt 3300 caatcctttg tattttctag tttagcgcca acttttgaca aaacctaaac tttagataat 3360 catcattctt acaattttta tctggatggc aataatctcc tatataaagc ccagataaac 3420 tgtaaaaaga atccatcact atttgaaaaa aagtcatctg gcacgtttaa ttatcagagc 3480 agaaatgatg aagggtgtta gcgccgtcca ttgatgcgcc tggtagtcat gatttacgta 3540 taactaacac atcatgagga cggc 3564 <210> 78 <211> 11114 <212> DNA <213> Artificial Sequence <220> <223> SEQ ID NO:78 (DiPKS-1) <400> 78 tggaccactt cttcttggac ttcttaccac cagcaagagc ggcagcggct ttggcagctt 60 tagacaattg ttgctttgga ggcatgttat attatgttct gagacgtaag aaagggtgaa 120 aattgatgtt agtgtcaaaa attatattac aaaatacgca gagatattct agttcctttg 180 atgaatgaat ctttcagaaa aaaaagtcaa agcaaaagca aaatggcctg cagactaaac 240 tgtatggtgg tcttggaatg ataaagatct gtttaataga tttagtagat acaatagcac 300 atctcattac ccagttatga ttgacgtcat tctgagttac aatgatctta agcaacaggc 360 gcgttggact tttaattttc gaggaccgcg aatccttaca tcacacccaa tcccccacaa 420 gtgatccccc acacaccata gcttcaaaat gtttctactc cttttttact cttccagatt 480 ttctcggact ccgcgcatcg ccgtaccact tcaaaacacc caagcacagc atactaaatt 540 tcccctcttt cttcctctag ggtgtcgtta attacccgta ctaaaggttt ggaaaagaaa 600 aaagagaccg cctcgtttct ttttcttcgt cgaaaaaggc aataaaaatt tttatcacgt 660 ttctttttct tgaaaatttt tttttttgat ttttttctct ttcgatgacc tcccattgat 720 atttaagtta ataaacggtc ttcaatttct caagtttcag tttcattttt cttgttctat 780 tacaactttt tttacttctt gctcattaga aagaaagcat agcaatctaa tctaagtttt 840 aataaacaat gaacaagaac tccaaaatcc agtccccaaa ctcttctgat gttgctgtta 900 ttggtgttgg ttttagattc ccaggtaact ctaatgaccc agaatctttg tggaacaact 960 tgttggatgg tttcgatgct attacccaag tcccaaaaga aagatgggct acttctttta 1020 gagagatggg tttgatcaag aacaagttcg gtggtttctt gaaggattct gaatggaaga 1080 atttcgaccc tttgttcttt ggtatcggtc caaaagaagc tccattcatt gatccacaac 1140 aaaggttgtt gttgtccatc gtttgggaat ctttggaaga tgcttacatc agaccagatg 1200 aattgagagg ttctaacact ggtgttttca tcggtgtttc taacaacgat tacaccaagt 1260 tgggtttcca agacaactac tctatttctc catacactat gaccggctct aactcttcat 1320 tgaactccaa cagaatttcc tactgcttcg attttagagg tccatccatt actgttgata 1380 ccgcttgttc ttcttccttg gtttctgtta atttgggtgt ccaatccatc caaatgggtg 1440 aatgtaagat tgctatttgc ggtggtgtta acgctttgtt tgatccatct acatctgttg 1500 ccttttccaa gttgggtgtt ttgtctgaaa atggcagatg caactctttt agtgatcaag 1560 cctctggtta cgttagatct gaaggtgctg gtgttgttgt tttgaagtct ttggaacaag 1620 ctaagttgga tggtgataga atctacggtg ttatcaaggg tgtttcctct aatgaagatg 1680 gtgcttctaa tggtgacaag aactctttga ctactccatc ttgtgaagcc caatccatta 1740 acatttctaa ggctatggaa aaggcctcct tgtctccatc tgatatctat tacattgaag 1800 cccatggtac tggtactcca gttggtgatc caattgaagt taaggccttg tccaagatct 1860 tctccaactc taacaacaac cagttgaaca acttctctac cgatggtaat gataacgatg 1920 atgatgatga cgataacacc tctccagaac cattattgat tggctcattc aagtccaaca 1980 tcggtcattt ggaatctgct gctggtattg cttctttgat taagtgttgc ttgatgttga 2040 agaacaggat gttggttcca tccattaact gctctaattt gaacccatcc attccattcg 2100 atcagtacaa catctccgtt atcagagaaa tcagacaatt cccaaccgat aagttggtta 2160 acatcggtat caattctttc ggtttcggtg gttctaactg ccatttgatt attcaagagt 2220 acaacaacaa cttcaagaac aactctacca tctgcaataa caacaacaac aacaataaca 2280 acatcgacta cttgatccca atctcctcta agactaagaa gtccttggat aagtacttga 2340 ttttgatcaa gaccaactcc aactaccaca aggatatttc tttcgatgac ttcgtcaagt 2400 tccaaatcaa gtctaagcag tacaacttgt ccaacagaat gactaccatt gctaacgatt 2460 ggaactcctt cattaagggt tctaacgaat tccacaactt gatcgaatct aaggatggtg 2520 aaggtggttc ttcatcttct aacagaggta ttgattccgc caatcaaatc aacactacta 2580 ctacctctac catcaacgat atcgaacctt tgttggtttt cgttttctgt ggtcaaggtc 2640 cacaatggaa tggtatgatt aagaccttgt acaactccga gaacgttttc aagaacaccg 2700 ttgatcatgt tgacagcatc ttgtacaagt acttcggtta ctccattttg aacgtcttgt 2760 ctaagatcga tgataacgac gattccatca accatccaat agttgctcaa ccatctttgt 2820 tcttgttgca aattggtttg gtcgagttgt ttaagtactg gggtatctac ccatctatct 2880 ctgttggtca ttctttcggt gaagtctctt cttattactt gtccggtatc atctctttgg 2940 aaaccgcttg taaaatcgtc tacgtcagat cctctaatca gaacaaaact atgggttccg 3000 gtaagatgtt ggttgtttct atgggtttta agcaatggaa cgatcaattc tctgctgaat 3060 ggtccgatat tgaaattgct tgttacaacg ctccagattc catagttgtt actggtaacg 3120 aagaaagatt gaaagaattg tccatcaagt tgtccgacga atccaatcaa attttcaaca 3180 ccttcttgag gtccccatgt tcttttcatt cttcccatca agaagtcatc aagggttcta 3240 tgttcgaaga gttgtctaac ttgcaatcta ctggtgaaac cgaaatccct ttgttctcta 3300 ctgttactgg tagacaagtt ttgtctggtc atgttactgc tcaacacatc tacgataatg 3360 ttagagaacc agtcttgttc caaaagacga ttgaatccat tacctcctac atcaagtctc 3420 actacccatc caatcaaaag gttatctacg ttgaaattgc tccacaccca accttgtttt 3480 cattgatcaa aaagtccatc ccatcctcca acaagaattc ctcttctgtt ttgtgtccat 3540 tgaacagaaa agaaaactcc aacaactcct acaagaagtt cgtttctcag ttgtacttca 3600 acggtgttaa cgttgacttc aacttccagt tgaactccat ttgcgataac gttaacaacg 3660 atcaccattt gaacaacgtc aagcaaaact ccttcaaaga gactaccaat tccttgccaa 3720 gataccaatg ggaacaagat gaatattggt ccgaaccatt gatctccaga aagaatagat 3780 tggaaggtcc aactacttcc ttgttgggtc atagaattat ctacagcttc ccagttttcc 3840 aatccgtttt ggacttgcaa tctgacaact acaaatactt gttggaccac ttggttaacg 3900 gtaagccagt ttttccaggt gctggttatt tggatatcat catcgaattc ttcgactacc 3960 aaaagcagca gttgaattcc tctgattcct ctaactccta catcatcaac gttgacaaga 4020 tccaattctt gaacccaatt cacttgaccg aaaacaagtt gcaaaccttg caatcttctt 4080 tcgaacctat cgttactaag aagtctgcct tctctgttaa cttcttcatc aaggataccg 4140 tcgaggatca atctaaggtt aagtctatgt ctgacgaaac ttggactaac acttgtaagg 4200 ctaccatttc cttggaacaa caacagccat ctccatcttc tactttgact ttgtctaaga 4260 agcaagactt gcagatcttg agaaacagat gcgatattag caagctagac aagtttgagt 4320 tgtacgacaa gatctctaag aatttgggct tgcagtacaa ctccttgttt caagttgttg 4380 ataccatcga aactggtaag gattgctctt ttgctacttt gtctttgcca gaagatactt 4440 tgttcaccac cattttgaac ccatgcttgt tggataactg tttccatggt ttgttgacct 4500 tgatcaacga aaagggttct ttcgttgtcg agtccatttc ttctgtttct atctacttgg 4560 agaacatcgg ttccttcaat caaacttctg ttggtaacgt ccagttctac ttgtacacca 4620 ctatttctaa agccacctcc tttagttctg aaggtacttg taagttgttc accaaggatg 4680 gttccttgat tttgtctatc ggtaagttca tcatcaagtc caccaatcca aagtctacta 4740 agaccaacga aactatcgaa tctccattgg acgaaacctt ctctattgaa tggcaatcta 4800 aggattctcc aattccaacc ccacaacaaa tccaacaaca atctccattg aactctaacc 4860 catccttcat tagatctacc atcttgaagg acatccagtt cgaacaatac tgctcctcca 4920 ttatccacaa agaattgatc aaccacgaaa agtacaagaa ccagcaatcc ttcgatatca 4980 actccttgga aaaccacttg aacgatgacc aattgatgga atccttgtcc atctccaaag 5040 aatacttgag attcttcacc aggatcatct ccatcattaa gcaataccca aagatcttga 5100 acgaaaaaga gctaaaagaa ttgaaagaaa tcatcgaatt gaagtaccca tccgaagttc 5160 agttgttgga attcgaagtt atcgagaagg tgtccatgat tatcccaaag ttgttgttcg 5220 aaaacgacaa gcaatcttcc atgaccttgt tccaagataa cttgttgacc aggttctact 5280 ccaattctaa ctctaccaga ttctacttgg aaagggtttc cgaaatggtc ttggaatcta 5340 ttagaccaat cgtcagagaa aagagggtgt tcagaatttt agagatcggt gctcgtacag 5400 gctctttgtc taatgttgtt ttgactaagt tgaacaccta cttgtccacc ttgaattcta 5460 atggtggttc tggttacaac atcatcattg agtacacctt caccgatatt tccgccaact 5520 tcattattgg tgaaatccaa gaaaccatgt gcaacttgta cccaaacgtt actttcaagt 5580 tctccgtctt ggacttggag aaagagatta ttaactcctc cgatttcttg atgggtgatt 5640 acgatatagt tttgatggcc tacgttatcc atgccgtttc taacattaag ttctccatcg 5700 aacagttgta caagttgttg tctccaagag gttggttgtt gtgtattgaa cctaagtcca 5760 acgttgtgtt ctccgatttg gttttcggtt gttttaatca gtggtggaac tactacgatg 5820 atattagaac tacccactgc tccttgtctg aatctcaatg gaatcagttg ttgttgaacc 5880 agtccttgaa caacgaatcc tcttcttctt ctaactgtta cggtggtttc tccaacgttt 5940 cttttattgg tggtgaaaag gatgtcgact cccattcttt catattgcac tgccaaaaag 6000 aatccatctc ccaaatgaag ttagccacca ctattaacaa cggtttgtca tctggttcca 6060 tcgttatcgt tttgaactct caacaattga ccaacatgaa gtcctaccca aaggttattg 6120 agtatattca agaggctacc tctttgtgca agaccattga aattatcgat tccaaggacg 6180 tcttgaactc taccaattca gttttggaaa agatccaaaa gtccttgttg gtgttctgtt 6240 tgttgggtta tgacttgttg gagaacaact accaagaaca gtctttcgaa tacgttaagt 6300 tgttgaactt gatctctact accgcctctt catctaatga taagaaacca ccaaaggtct 6360 tgttgatcac caagcaatct gaaagaatct ccaggtcttt ctactccaga tccttgattg 6420 gtatttccag aacctctatg aacgagtacc caaatttgtc cattacctct atcgatttgg 6480 ataccaacga ctactcattg cagtctttgt tgaagccaat cttcagcaac tctaagtttt 6540 ccgacaacga gttcatcttc aaaaagggct tgatgttcgt gtccaggatc tttaagaaca 6600 agcagttgct agaatcctcc aacgcttttg aaactgactc ttctaacttg tactgtaagg 6660 cctcttctga cttgtcttac aagtacgcta ttaagcagtc tatgttgacc gaaaatcaga 6720 tcgaaatcaa ggttgaatgc gtcggtatta acttcaagga caacctattc tacaagggct 6780 tgttgccaca agaaattttc agaatgggtg acatctacaa tccaccatat ggtttggaat 6840 gctctggtgt tattaccaga attggttcta acgtcaccga atactcagtt ggtcaaaatg 6900 tttttggttt cgccagacat tctttgggtt ctcatgttgt taccaacaag gatttggtta 6960 tcttgaagcc agataccatc tcattttctg aagctgcttc tatcccagtt gtttactgta 7020 ctgcttggta ctccttgttc aacattggtc agttgtctaa cgaagaatcc atcctaattc 7080 attctgctac tggtggtgta ggtttggctt ctttgaattt gttgaaaatg aagaatcagc 7140 aacagcaacc attgaccaat gtttatgcta ctgttggctc taacgagaag aagaagttct 7200 tgatcgataa cttcaacaac ttgttcaaag aggacggcga aaacattttc tctaccagag 7260 acaaagaata ctccaaccag ttggaatcca agatcgatgt tattttgaac accttgtccg 7320 gtgaattcgt cgaatctaat ttcaagtcct tgagatcctt cggtagattg attgatttgt 7380 ctgctactca cgtttacgcc aatcaacaaa ttggtctagg taacttcaag ttcgaccact 7440 tgtattctgc tgttgacttg gaaagattga tcgacgaaaa acctaagttg ttgcagtcca 7500 tcttgcaaag aattaccaac tctatcgtca acggttcctt ggaaaaaatt ccaattacca 7560 tcttcccatc caccgaaact aaggatgcta tcgaattatt gtccaagaga tcccatatcg 7620 gtaaagttgt tgtagattgc accgatatct ctaagtgtaa tcctgttggt gatgtgatca 7680 ccaacttctc tatgagattg ccaaagccaa actaccagtt gaatttgaac tccaccttgt 7740 tgattactgg tcagtctggt ttgtctatcc ctttgttgaa ttggttgttg tctaagtctg 7800 gtggtaacgt taagaacgtt gtcatcattt ctaagtccac catgaagtgg aagttgcaga 7860 ctatgatttc ccatttcgtt tccggtttcg gtatccattt taactacgtt caagtcgaca 7920 tctccaacta cgatgctttg tctgaagcta ttaagcaatt gccatctgat ttgccaccaa 7980 tcacctctgt ttttcatttg gctgctatct acaacgatgt tccaatggat caagttacca 8040 tgtctaccgt tgaatctgtt cataacccta aagttttggg tgccgttaac ttgcatagaa 8100 tctctgtttc ttttggttgg aagttgaacc acttcgtctt gttctcttct attactgcta 8160 ttaccggtta cccagaccaa tctatctaca attctgccaa ctctattttg gacgctttgt 8220 ccaactttag aaggtttatg ggtttgccat ccttctccat taacttgggt ccaatgaagg 8280 atgaaggtaa ggtttctacc aacaagagca tcaagaagct attcaagtct agaggtttgc 8340 caagcctatc cttgaacaag ttatttggtt tgttggaggt cgtcatcaac aacccatcta 8400 atcatgttat cccatcccaa ttgatttgct ccccaatcga tttcaagacc tacatcgaat 8460 ctttctcaac tatgaggcca aagttgttac acttgcaacc taccatttcc aagcagcaat 8520 cttctatcat taacgattct accaaggctt cctccaacat ttcattgcaa gataagatca 8580 cctccaaggt gtctgatttg ttgtccattc caatctccaa gatcaacttc gatcatccat 8640 tgaaacacta cggcttggat tctttgttga ccgttcaatt caaatcctgg atcgacaaag 8700 aattcgaaaa gaacttgttc acccatatcc aattggccac catctctatt aactcattct 8760 tggaaaaggt gaacggcttg tctacaaaca ataacaacaa caacaattcc aacgtcaagt 8820 cctctccatc cattgtcaaa gaagaaatcg ttaccttgga caaggatcaa caaccattgc 8880 tattgaaaga acaccagcac attatcatct ccccagatat tagaatcaac aagccaaaga 8940 gggaatcctt gattagaacc ccaatcttga acaaattcaa ccagatcacc gaatccatta 9000 tcactccatc tacaccatct ttgtcccaat ccgatgtttt gaaaactcca ccaatcaagt 9060 ctttgaacaa cactaagaac tccagcttga ttaacacccc accaattcaa tctgtccaac 9120 aacatcaaaa gcaacaacaa aaggtccaag tcatccaaca acagcaacaa ccattatcca 9180 gattgtccta caagagcaac aacaactctt tcgttttggg tatcggtatt tctgttccag 9240 gtgaacctat ttcccaacaa tccttgaaag actccatctc caatgacttt tctgataagg 9300 ctgaaactaa cgagaaggtc aagagaatct ttgagcaatc tcaaatcaag accagacact 9360 tggttagaga ttacactaag ccagagaact ccatcaagtt cagacatttg gaaaccatta 9420 ccgatgtgaa caaccagttc aagaaagttg ttccagattt ggctcaacaa gcctgtttga 9480 gagctttgaa agattggggt ggtgataagg gtgatattac ccatatagtt tctgttacct 9540 ccaccggtat tatcatccca gatgttaatt tcaagttgat cgacttgttg ggcttgaaca 9600 aggatgttga aagagtgtct ttgaacctaa tgggttgttt ggctggtttg agttctttga 9660 gaactgctgc ttctttggct aaggcttctc caagaaatag aattttggtt gtctgtaccg 9720 aagtctgctc cttgcatttt tctaatactg atggtggtga tcaaatggtc gcctcttcta 9780 tttttgctga tggttctgct gcttacatta ttggttgtaa cccaagaatt gaagaaaccc 9840 cattatacga agtcatgtgc tccattaaca gatctttccc aaataccgaa aacgccatgg 9900 tttgggattt ggaaaaagaa ggttggaact tgggtttgga tgcttctatt ccaattgtca 9960 ttggttctgg tattgaagcc ttcgttgata ctttgttgga taaggctaag ttgcaaactt 10020 ccactgctat ttctgctaag gattgcgaat tcttgattca tactggtggc aagtccatct 10080 tgatgaacat cgaaaattcc ttgggtatcg acccaaagca aactaagaat acttgggatg 10140 tttaccatgc ctacggcaat atgtcatctg cctctgttat tttcgttatg gatcatgcca 10200 gaaagtccaa gtctttgcca acttactcaa tttctttggc ttttggtcca ggtttggctt 10260 ttgaaggttg tttcttgaag aacgtcgtct gaacagaaga cgggagacac tagcacacaa 10320 ctttaccagg caaggtattt gacgctagca tgtgtccaat tcagtgtcat ttatgatttt 10380 ttgtagtagg atataaatat atacagcgct ccaaatagtg cggttgcccc aaaaacacca 10440 cggaacctca tctgttctcg tactttgttg tgacaaagta gctcactgcc ttattatcac 10500 attttcatta tgcaacgctt cggaaaatac gatgttgaaa atgcctctag agatgaaaaa 10560 caatcgtaaa agggtcctgc gtaattgaaa catttgatca gtatgcagtg gcacagaaac 10620 aaccaggaat actatagtca taggcaatac aaggtatata ttggctatgc agacccctcc 10680 agaaagtacc gacgtcaagt tagatacact taacgaacct agtgcacatt taattgagaa 10740 aaatgtggct cttcctatgg acatattccg ttcgtacttg agttattgga tctatgaaat 10800 cgctcgctat acaccagtca tgattttgtc gaagttatta tccaggaggc acggatgcaa 10860 aagatagaag acaaattaat ttccttaaaa ttcaaaatgc tcattattgt cacgctgtat 10920 gagcatttgg tgaagatttc actgggaaat gttgcaataa tttgataatc gttcgtattg 10980 gatgaaactg taacatcatc tgtttattaa gtatccgtgt tattagtata tcatcacata 11040 cggtgtaaga agataacata aagattgaga aacagtcatc aaatataatg gaagctgaaa 11100 tgcgaggatt gatg 11114 <210> 79 <211> 10890 <212> DNA <213> Artificial Sequence <220> <223> DiPKS-2 <400> 79 acgatgattc agttcgcctt ctatcctttg tttacgtatt tgtttatata tataacttta 60 ttttttttta ttaattgggc tgcaagacaa ttttgttgtc agtgatgcct caatccttct 120 tttgcttcca tatttaccat gtggaccctt tcaaaacaga gttgtatctc tgcaggatgc 180 cctttttgac gtattgaatg gcataattgc actgtcaaag caacaggcgc gttggacttt 240 taattttcga ggaccgcgaa tccttacatc acacccaatc ccccacaagt gatcccccac 300 acaccatagc ttcaaaatgt ttctactcct tttttactct tccagatttt ctcggactcc 360 gcgcatcgcc gtaccacttc aaaacaccca agcacagcat actaaatttc ccctctttct 420 tcctctaggg tgtcgttaat tacccgtact aaaggtttgg aaaagaaaaa agagaccgcc 480 tcgtttcttt ttcttcgtcg aaaaaggcaa taaaaatttt tatcacgttt ctttttcttg 540 aaaatttttt tttttgattt ttttctcttt cgatgacctc ccattgatat ttaagttaat 600 aaacggtctt caatttctca agtttcagtt tcatttttct tgttctatta caactttttt 660 tacttcttgc tcattagaaa gaaagcatag caatctaatc taagttttaa taaacaatga 720 acaagaactc caaaatccag tccccaaact cttctgatgt tgctgttatt ggtgttggtt 780 ttagattccc aggtaactct aatgacccag aatctttgtg gaacaacttg ttggatggtt 840 tcgatgctat tacccaagtc ccaaaagaaa gatgggctac ttcttttaga gagatgggtt 900 tgatcaagaa caagttcggt ggtttcttga aggattctga atggaagaat ttcgaccctt 960 tgttctttgg tatcggtcca aaagaagctc cattcattga tccacaacaa aggttgttgt 1020 tgtccatcgt ttgggaatct ttggaagatg cttacatcag accagatgaa ttgagaggtt 1080 ctaacactgg tgttttcatc ggtgtttcta acaacgatta caccaagttg ggtttccaag 1140 acaactactc tatttctcca tacactatga ccggctctaa ctcttcattg aactccaaca 1200 gaatttccta ctgcttcgat tttagaggtc catccattac tgttgatacc gcttgttctt 1260 cttccttggt ttctgttaat ttgggtgtcc aatccatcca aatgggtgaa tgtaagattg 1320 ctatttgcgg tggtgttaac gctttgtttg atccatctac atctgttgcc ttttccaagt 1380 tgggtgtttt gtctgaaaat ggcagatgca actcttttag tgatcaagcc tctggttacg 1440 ttagatctga aggtgctggt gttgttgttt tgaagtcttt ggaacaagct aagttggatg 1500 gtgatagaat ctacggtgtt atcaagggtg tttcctctaa tgaagatggt gcttctaatg 1560 gtgacaagaa ctctttgact actccatctt gtgaagccca atccattaac atttctaagg 1620 ctatggaaaa ggcctccttg tctccatctg atatctatta cattgaagcc catggtactg 1680 gtactccagt tggtgatcca attgaagtta aggccttgtc caagatcttc tccaactcta 1740 acaacaacca gttgaacaac ttctctaccg atggtaatga taacgatgat gatgatgacg 1800 ataacacctc tccagaacca ttattgattg gctcattcaa gtccaacatc ggtcatttgg 1860 aatctgctgc tggtattgct tctttgatta agtgttgctt gatgttgaag aacaggatgt 1920 tggttccatc cattaactgc tctaatttga acccatccat tccattcgat cagtacaaca 1980 tctccgttat cagagaaatc agacaattcc caaccgataa gttggttaac atcggtatca 2040 attctttcgg tttcggtggt tctaactgcc atttgattat tcaagagtac aacaacaact 2100 tcaagaacaa ctctaccatc tgcaataaca acaacaacaa caataacaac atcgactact 2160 tgatcccaat ctcctctaag actaagaagt ccttggataa gtacttgatt ttgatcaaga 2220 ccaactccaa ctaccacaag gatatttctt tcgatgactt cgtcaagttc caaatcaagt 2280 ctaagcagta caacttgtcc aacagaatga ctaccattgc taacgattgg aactccttca 2340 ttaagggttc taacgaattc cacaacttga tcgaatctaa ggatggtgaa ggtggttctt 2400 catcttctaa cagaggtatt gattccgcca atcaaatcaa cactactact acctctacca 2460 tcaacgatat cgaacctttg ttggttttcg ttttctgtgg tcaaggtcca caatggaatg 2520 gtatgattaa gaccttgtac aactccgaga acgttttcaa gaacaccgtt gatcatgttg 2580 acagcatctt gtacaagtac ttcggttact ccattttgaa cgtcttgtct aagatcgatg 2640 ataacgacga ttccatcaac catccaatag ttgctcaacc atctttgttc ttgttgcaaa 2700 ttggtttggt cgagttgttt aagtactggg gtatctaccc atctatctct gttggtcatt 2760 ctttcggtga agtctcttct tattacttgt ccggtatcat ctctttggaa accgcttgta 2820 aaatcgtcta cgtcagatcc tctaatcaga acaaaactat gggttccggt aagatgttgg 2880 ttgtttctat gggttttaag caatggaacg atcaattctc tgctgaatgg tccgatattg 2940 aaattgcttg ttacaacgct ccagattcca tagttgttac tggtaacgaa gaaagattga 3000 aagaattgtc catcaagttg tccgacgaat ccaatcaaat tttcaacacc ttcttgaggt 3060 ccccatgttc ttttcattct tcccatcaag aagtcatcaa gggttctatg ttcgaagagt 3120 tgtctaactt gcaatctact ggtgaaaccg aaatcccttt gttctctact gttactggta 3180 gacaagtttt gtctggtcat gttactgctc aacacatcta cgataatgtt agagaaccag 3240 tcttgttcca aaagacgatt gaatccatta cctcctacat caagtctcac tacccatcca 3300 atcaaaaggt tatctacgtt gaaattgctc cacacccaac cttgttttca ttgatcaaaa 3360 agtccatccc atcctccaac aagaattcct cttctgtttt gtgtccattg aacagaaaag 3420 aaaactccaa caactcctac aagaagttcg tttctcagtt gtacttcaac ggtgttaacg 3480 ttgacttcaa cttccagttg aactccattt gcgataacgt taacaacgat caccatttga 3540 acaacgtcaa gcaaaactcc ttcaaagaga ctaccaattc cttgccaaga taccaatggg 3600 aacaagatga atattggtcc gaaccattga tctccagaaa gaatagattg gaaggtccaa 3660 ctacttcctt gttgggtcat agaattatct acagcttccc agttttccaa tccgttttgg 3720 acttgcaatc tgacaactac aaatacttgt tggaccactt ggttaacggt aagccagttt 3780 ttccaggtgc tggttatttg gatatcatca tcgaattctt cgactaccaa aagcagcagt 3840 tgaattcctc tgattcctct aactcctaca tcatcaacgt tgacaagatc caattcttga 3900 acccaattca cttgaccgaa aacaagttgc aaaccttgca atcttctttc gaacctatcg 3960 ttactaagaa gtctgccttc tctgttaact tcttcatcaa ggataccgtc gaggatcaat 4020 ctaaggttaa gtctatgtct gacgaaactt ggactaacac ttgtaaggct accatttcct 4080 tggaacaaca acagccatct ccatcttcta ctttgacttt gtctaagaag caagacttgc 4140 agatcttgag aaacagatgc gatattagca agctagacaa gtttgagttg tacgacaaga 4200 tctctaagaa tttgggcttg cagtacaact ccttgtttca agttgttgat accatcgaaa 4260 ctggtaagga ttgctctttt gctactttgt ctttgccaga agatactttg ttcaccacca 4320 ttttgaaccc atgcttgttg gataactgtt tccatggttt gttgaccttg atcaacgaaa 4380 agggttcttt cgttgtcgag tccatttctt ctgtttctat ctacttggag aacatcggtt 4440 ccttcaatca aacttctgtt ggtaacgtcc agttctactt gtacaccact atttctaaag 4500 ccacctcctt tagttctgaa ggtacttgta agttgttcac caaggatggt tccttgattt 4560 tgtctatcgg taagttcatc atcaagtcca ccaatccaaa gtctactaag accaacgaaa 4620 ctatcgaatc tccattggac gaaaccttct ctattgaatg gcaatctaag gattctccaa 4680 ttccaacccc acaacaaatc caacaacaat ctccattgaa ctctaaccca tccttcatta 4740 gatctaccat cttgaaggac atccagttcg aacaatactg ctcctccatt atccacaaag 4800 aattgatcaa ccacgaaaag tacaagaacc agcaatcctt cgatatcaac tccttggaaa 4860 accacttgaa cgatgaccaa ttgatggaat ccttgtccat ctccaaagaa tacttgagat 4920 tcttcaccag gatcatctcc atcattaagc aatacccaaa gatcttgaac gaaaaagagc 4980 taaaagaatt gaaagaaatc atcgaattga agtacccatc cgaagttcag ttgttggaat 5040 tcgaagttat cgagaaggtg tccatgatta tcccaaagtt gttgttcgaa aacgacaagc 5100 aatcttccat gaccttgttc caagataact tgttgaccag gttctactcc aattctaact 5160 ctaccagatt ctacttggaa agggtttccg aaatggtctt ggaatctatt agaccaatcg 5220 tcagagaaaa gagggtgttc agaattttag agatcggtgc tcgtacaggc tctttgtcta 5280 atgttgtttt gactaagttg aacacctact tgtccacctt gaattctaat ggtggttctg 5340 gttacaacat catcattgag tacaccttca ccgatatttc cgccaacttc attattggtg 5400 aaatccaaga aaccatgtgc aacttgtacc caaacgttac tttcaagttc tccgtcttgg 5460 acttggagaa agagattatt aactcctccg atttcttgat gggtgattac gatatagttt 5520 tgatggccta cgttatccat gccgtttcta acattaagtt ctccatcgaa cagttgtaca 5580 agttgttgtc tccaagaggt tggttgttgt gtattgaacc taagtccaac gttgtgttct 5640 ccgatttggt tttcggttgt tttaatcagt ggtggaacta ctacgatgat attagaacta 5700 cccactgctc cttgtctgaa tctcaatgga atcagttgtt gttgaaccag tccttgaaca 5760 acgaatcctc ttcttcttct aactgttacg gtggtttctc caacgtttct tttattggtg 5820 gtgaaaagga tgtcgactcc cattctttca tattgcactg ccaaaaagaa tccatctccc 5880 aaatgaagtt agccaccact attaacaacg gtttgtcatc tggttccatc gttatcgttt 5940 tgaactctca acaattgacc aacatgaagt cctacccaaa ggttattgag tatattcaag 6000 aggctacctc tttgtgcaag accattgaaa ttatcgattc caaggacgtc ttgaactcta 6060 ccaattcagt tttggaaaag atccaaaagt ccttgttggt gttctgtttg ttgggttatg 6120 acttgttgga gaacaactac caagaacagt ctttcgaata cgttaagttg ttgaacttga 6180 tctctactac cgcctcttca tctaatgata agaaaccacc aaaggtcttg ttgatcacca 6240 agcaatctga aagaatctcc aggtctttct actccagatc cttgattggt atttccagaa 6300 cctctatgaa cgagtaccca aatttgtcca ttacctctat cgatttggat accaacgact 6360 actcattgca gtctttgttg aagccaatct tcagcaactc taagttttcc gacaacgagt 6420 tcatcttcaa aaagggcttg atgttcgtgt ccaggatctt taagaacaag cagttgctag 6480 aatcctccaa cgcttttgaa actgactctt ctaacttgta ctgtaaggcc tcttctgact 6540 tgtcttacaa gtacgctatt aagcagtcta tgttgaccga aaatcagatc gaaatcaagg 6600 ttgaatgcgt cggtattaac ttcaaggaca acctattcta caagggcttg ttgccacaag 6660 aaattttcag aatgggtgac atctacaatc caccatatgg tttggaatgc tctggtgtta 6720 ttaccagaat tggttctaac gtcaccgaat actcagttgg tcaaaatgtt tttggtttcg 6780 ccagacattc tttgggttct catgttgtta ccaacaagga tttggttatc ttgaagccag 6840 ataccatctc attttctgaa gctgcttcta tcccagttgt ttactgtact gcttggtact 6900 ccttgttcaa cattggtcag ttgtctaacg aagaatccat cctaattcat tctgctactg 6960 gtggtgtagg tttggcttct ttgaatttgt tgaaaatgaa gaatcagcaa cagcaaccat 7020 tgaccaatgt ttatgctact gttggctcta acgagaagaa gaagttcttg atcgataact 7080 tcaacaactt gttcaaagag gacggcgaaa acattttctc taccagagac aaagaatact 7140 ccaaccagtt ggaatccaag atcgatgtta ttttgaacac cttgtccggt gaattcgtcg 7200 aatctaattt caagtccttg agatccttcg gtagattgat tgatttgtct gctactcacg 7260 tttacgccaa tcaacaaatt ggtctaggta acttcaagtt cgaccacttg tattctgctg 7320 ttgacttgga aagattgatc gacgaaaaac ctaagttgtt gcagtccatc ttgcaaagaa 7380 ttaccaactc tatcgtcaac ggttccttgg aaaaaattcc aattaccatc ttcccatcca 7440 ccgaaactaa ggatgctatc gaattattgt ccaagagatc ccatatcggt aaagttgttg 7500 tagattgcac cgatatctct aagtgtaatc ctgttggtga tgtgatcacc aacttctcta 7560 tgagattgcc aaagccaaac taccagttga atttgaactc caccttgttg attactggtc 7620 agtctggttt gtctatccct ttgttgaatt ggttgttgtc taagtctggt ggtaacgtta 7680 agaacgttgt catcatttct aagtccacca tgaagtggaa gttgcagact atgatttccc 7740 atttcgtttc cggtttcggt atccatttta actacgttca agtcgacatc tccaactacg 7800 atgctttgtc tgaagctatt aagcaattgc catctgattt gccaccaatc acctctgttt 7860 ttcatttggc tgctatctac aacgatgttc caatggatca agttaccatg tctaccgttg 7920 aatctgttca taaccctaaa gttttgggtg ccgttaactt gcatagaatc tctgtttctt 7980 ttggttggaa gttgaaccac ttcgtcttgt tctcttctat tactgctatt accggttacc 8040 cagaccaatc tatctacaat tctgccaact ctattttgga cgctttgtcc aactttagaa 8100 ggtttatggg tttgccatcc ttctccatta acttgggtcc aatgaaggat gaaggtaagg 8160 tttctaccaa caagagcatc aagaagctat tcaagtctag aggtttgcca agcctatcct 8220 tgaacaagtt atttggtttg ttggaggtcg tcatcaacaa cccatctaat catgttatcc 8280 catcccaatt gatttgctcc ccaatcgatt tcaagaccta catcgaatct ttctcaacta 8340 tgaggccaaa gttgttacac ttgcaaccta ccatttccaa gcagcaatct tctatcatta 8400 acgattctac caaggcttcc tccaacattt cattgcaaga taagatcacc tccaaggtgt 8460 ctgatttgtt gtccattcca atctccaaga tcaacttcga tcatccattg aaacactacg 8520 gcttggattc tttgttgacc gttcaattca aatcctggat cgacaaagaa ttcgaaaaga 8580 acttgttcac ccatatccaa ttggccacca tctctattaa ctcattcttg gaaaaggtga 8640 acggcttgtc tacaaacaat aacaacaaca acaattccaa cgtcaagtcc tctccatcca 8700 ttgtcaaaga agaaatcgtt accttggaca aggatcaaca accattgcta ttgaaagaac 8760 accagcacat tatcatctcc ccagatatta gaatcaacaa gccaaagagg gaatccttga 8820 ttagaacccc aatcttgaac aaattcaacc agatcaccga atccattatc actccatcta 8880 caccatcttt gtcccaatcc gatgttttga aaactccacc aatcaagtct ttgaacaaca 8940 ctaagaactc cagcttgatt aacaccccac caattcaatc tgtccaacaa catcaaaagc 9000 aacaacaaaa ggtccaagtc atccaacaac agcaacaacc attatccaga ttgtcctaca 9060 agagcaacaa caactctttc gttttgggta tcggtatttc tgttccaggt gaacctattt 9120 cccaacaatc cttgaaagac tccatctcca atgacttttc tgataaggct gaaactaacg 9180 agaaggtcaa gagaatcttt gagcaatctc aaatcaagac cagacacttg gttagagatt 9240 acactaagcc agagaactcc atcaagttca gacatttgga aaccattacc gatgtgaaca 9300 accagttcaa gaaagttgtt ccagatttgg ctcaacaagc ctgtttgaga gctttgaaag 9360 attggggtgg tgataagggt gatattaccc atatagtttc tgttacctcc accggtatta 9420 tcatcccaga tgttaatttc aagttgatcg acttgttggg cttgaacaag gatgttgaaa 9480 gagtgtcttt gaacctaatg ggttgtttgg ctggtttgag ttctttgaga actgctgctt 9540 ctttggctaa ggcttctcca agaaatagaa ttttggttgt ctgtaccgaa gtctgctcct 9600 tgcatttttc taatactgat ggtggtgatc aaatggtcgc ctcttctatt tttgctgatg 9660 gttctgctgc ttacattatt ggttgtaacc caagaattga agaaacccca ttatacgaag 9720 tcatgtgctc cattaacaga tctttcccaa ataccgaaaa cgccatggtt tgggatttgg 9780 aaaaagaagg ttggaacttg ggtttggatg cttctattcc aattgtcatt ggttctggta 9840 ttgaagcctt cgttgatact ttgttggata aggctaagtt gcaaacttcc actgctattt 9900 ctgctaagga ttgcgaattc ttgattcata ctggtggcaa gtccatcttg atgaacatcg 9960 aaaattcctt gggtatcgac ccaaagcaaa ctaagaatac ttgggatgtt taccatgcct 10020 acggcaatat gtcatctgcc tctgttattt tcgttatgga tcatgccaga aagtccaagt 10080 ctttgccaac ttactcaatt tctttggctt ttggtccagg tttggctttt gaaggttgtt 10140 tcttgaagaa cgtcgtctga acagaagacg ggagacacta gcacacaact ttaccaggca 10200 aggtatttga cgctagcatg tgtccaattc agtgtcattt atgatttttt gtagtaggat 10260 ataaatatat acagcgctcc aaatagtgcg gttgccccaa aaacaccacg gaacctcatc 10320 tgttctcgta ctttgttgtg acaaagtagc tcactgcctt attatcacat tttcattatg 10380 caacgcttcg gaaaatacga tgttgaaaat gcctctagag atgaaaaaca atcgtaaaag 10440 ggtcctgcgt aattgaaaca tttgatcagt atgcagtggc acagaaacaa ccaggaatac 10500 tatagtcata ggcaatacaa ggtatatatt ggctatgcag acccctccag aaagtaccga 10560 cgtcaagtta gatacactta acgaacctag tgcacattta attgagaaaa atgtggctct 10620 tcctaaggac atattccgtt cgtacttgag ttattggatc tatgaaatcg ctcgctatac 10680 accagtcatg attttgtcta tgtgttgctc ttaaaatatt tggatacgac atcctttatc 10740 ttttttcctt taagagcagg atataagcca tcaagtttct gaaaatcaaa atggtagcaa 10800 caataatgca gacgacaaca actgtgctga cgacagtcgc cgcaatgtct actaccttag 10860 catcaaatta catatcttcg caagctagtt 10890 <210> 80 <211> 11300 <212> DNA <213> Artificial Sequence <220> <223> DiPKS-3 <400> 80 cgggttacag tcatcgttga aaacgatgga aaaacatgtc gagattcctc aatccataca 60 ccattatagt ccgttttatc agcttccact aattttttaa atctcagttt cttcttgaaa 120 tttagcatcg tgcatgggat agcggctagt aaaaaagaaa attaatatct cattaacaaa 180 gttattgtac ataatccggt acaatattct tcaatgtact ctctaatatc gagcacactg 240 gcaatattca tgcacacatt cgcctaatgc tgacgaatgc ttaatcagtg caattaagca 300 acaggcgcgt tggactttta attttcgagg accgcgaatc cttacatcac acccaatccc 360 ccacaagtga tcccccacac accatagctt caaaatgttt ctactccttt tttactcttc 420 cagattttct cggactccgc gcatcgccgt accacttcaa aacacccaag cacagcatac 480 taaatttccc ctctttcttc ctctagggtg tcgttaatta cccgtactaa aggtttggaa 540 aagaaaaaag agaccgcctc gtttcttttt cttcgtcgaa aaaggcaata aaaattttta 600 tcacgtttct ttttcttgaa aatttttttt tttgattttt ttctctttcg atgacctccc 660 attgatattt aagttaataa acggtcttca atttctcaag tttcagtttc atttttcttg 720 ttctattaca acttttttta cttcttgctc attagaaaga aagcatagca atctaatcta 780 agttttaata aacaatgaac aagaactcca aaatccagtc cccaaactct tctgatgttg 840 ctgttattgg tgttggtttt agattcccag gtaactctaa tgacccagaa tctttgtgga 900 acaacttgtt ggatggtttc gatgctatta cccaagtccc aaaagaaaga tgggctactt 960 cttttagaga gatgggtttg atcaagaaca agttcggtgg tttcttgaag gattctgaat 1020 ggaagaattt cgaccctttg ttctttggta tcggtccaaa agaagctcca ttcattgatc 1080 cacaacaaag gttgttgttg tccatcgttt gggaatcttt ggaagatgct tacatcagac 1140 cagatgaatt gagaggttct aacactggtg ttttcatcgg tgtttctaac aacgattaca 1200 ccaagttggg tttccaagac aactactcta tttctccata cactatgacc ggctctaact 1260 cttcattgaa ctccaacaga atttcctact gcttcgattt tagaggtcca tccattactg 1320 ttgataccgc ttgttcttct tccttggttt ctgttaattt gggtgtccaa tccatccaaa 1380 tgggtgaatg taagattgct atttgcggtg gtgttaacgc tttgtttgat ccatctacat 1440 ctgttgcctt ttccaagttg ggtgttttgt ctgaaaatgg cagatgcaac tcttttagtg 1500 atcaagcctc tggttacgtt agatctgaag gtgctggtgt tgttgttttg aagtctttgg 1560 aacaagctaa gttggatggt gatagaatct acggtgttat caagggtgtt tcctctaatg 1620 aagatggtgc ttctaatggt gacaagaact ctttgactac tccatcttgt gaagcccaat 1680 ccattaacat ttctaaggct atggaaaagg cctccttgtc tccatctgat atctattaca 1740 ttgaagccca tggtactggt actccagttg gtgatccaat tgaagttaag gccttgtcca 1800 agatcttctc caactctaac aacaaccagt tgaacaactt ctctaccgat ggtaatgata 1860 acgatgatga tgatgacgat aacacctctc cagaaccatt attgattggc tcattcaagt 1920 ccaacatcgg tcatttggaa tctgctgctg gtattgcttc tttgattaag tgttgcttga 1980 tgttgaagaa caggatgttg gttccatcca ttaactgctc taatttgaac ccatccattc 2040 cattcgatca gtacaacatc tccgttatca gagaaatcag acaattccca accgataagt 2100 tggttaacat cggtatcaat tctttcggtt tcggtggttc taactgccat ttgattattc 2160 aagagtacaa caacaacttc aagaacaact ctaccatctg caataacaac aacaacaaca 2220 ataacaacat cgactacttg atcccaatct cctctaagac taagaagtcc ttggataagt 2280 acttgatttt gatcaagacc aactccaact accacaagga tatttctttc gatgacttcg 2340 tcaagttcca aatcaagtct aagcagtaca acttgtccaa cagaatgact accattgcta 2400 acgattggaa ctccttcatt aagggttcta acgaattcca caacttgatc gaatctaagg 2460 atggtgaagg tggttcttca tcttctaaca gaggtattga ttccgccaat caaatcaaca 2520 ctactactac ctctaccatc aacgatatcg aacctttgtt ggttttcgtt ttctgtggtc 2580 aaggtccaca atggaatggt atgattaaga ccttgtacaa ctccgagaac gttttcaaga 2640 acaccgttga tcatgttgac agcatcttgt acaagtactt cggttactcc attttgaacg 2700 tcttgtctaa gatcgatgat aacgacgatt ccatcaacca tccaatagtt gctcaaccat 2760 ctttgttctt gttgcaaatt ggtttggtcg agttgtttaa gtactggggt atctacccat 2820 ctatctctgt tggtcattct ttcggtgaag tctcttctta ttacttgtcc ggtatcatct 2880 ctttggaaac cgcttgtaaa atcgtctacg tcagatcctc taatcagaac aaaactatgg 2940 gttccggtaa gatgttggtt gtttctatgg gttttaagca atggaacgat caattctctg 3000 ctgaatggtc cgatattgaa attgcttgtt acaacgctcc agattccata gttgttactg 3060 gtaacgaaga aagattgaaa gaattgtcca tcaagttgtc cgacgaatcc aatcaaattt 3120 tcaacacctt cttgaggtcc ccatgttctt ttcattcttc ccatcaagaa gtcatcaagg 3180 gttctatgtt cgaagagttg tctaacttgc aatctactgg tgaaaccgaa atccctttgt 3240 tctctactgt tactggtaga caagttttgt ctggtcatgt tactgctcaa cacatctacg 3300 ataatgttag agaaccagtc ttgttccaaa agacgattga atccattacc tcctacatca 3360 agtctcacta cccatccaat caaaaggtta tctacgttga aattgctcca cacccaacct 3420 tgttttcatt gatcaaaaag tccatcccat cctccaacaa gaattcctct tctgttttgt 3480 gtccattgaa cagaaaagaa aactccaaca actcctacaa gaagttcgtt tctcagttgt 3540 acttcaacgg tgttaacgtt gacttcaact tccagttgaa ctccatttgc gataacgtta 3600 acaacgatca ccatttgaac aacgtcaagc aaaactcctt caaagagact accaattcct 3660 tgccaagata ccaatgggaa caagatgaat attggtccga accattgatc tccagaaaga 3720 atagattgga aggtccaact acttccttgt tgggtcatag aattatctac agcttcccag 3780 ttttccaatc cgttttggac ttgcaatctg acaactacaa atacttgttg gaccacttgg 3840 ttaacggtaa gccagttttt ccaggtgctg gttatttgga tatcatcatc gaattcttcg 3900 actaccaaaa gcagcagttg aattcctctg attcctctaa ctcctacatc atcaacgttg 3960 acaagatcca attcttgaac ccaattcact tgaccgaaaa caagttgcaa accttgcaat 4020 cttctttcga acctatcgtt actaagaagt ctgccttctc tgttaacttc ttcatcaagg 4080 ataccgtcga ggatcaatct aaggttaagt ctatgtctga cgaaacttgg actaacactt 4140 gtaaggctac catttccttg gaacaacaac agccatctcc atcttctact ttgactttgt 4200 ctaagaagca agacttgcag atcttgagaa acagatgcga tattagcaag ctagacaagt 4260 ttgagttgta cgacaagatc tctaagaatt tgggcttgca gtacaactcc ttgtttcaag 4320 ttgttgatac catcgaaact ggtaaggatt gctcttttgc tactttgtct ttgccagaag 4380 atactttgtt caccaccatt ttgaacccat gcttgttgga taactgtttc catggtttgt 4440 tgaccttgat caacgaaaag ggttctttcg ttgtcgagtc catttcttct gtttctatct 4500 acttggagaa catcggttcc ttcaatcaaa cttctgttgg taacgtccag ttctacttgt 4560 acaccactat ttctaaagcc acctccttta gttctgaagg tacttgtaag ttgttcacca 4620 aggatggttc cttgattttg tctatcggta agttcatcat caagtccacc aatccaaagt 4680 ctactaagac caacgaaact atcgaatctc cattggacga aaccttctct attgaatggc 4740 aatctaagga ttctccaatt ccaaccccac aacaaatcca acaacaatct ccattgaact 4800 ctaacccatc cttcattaga tctaccatct tgaaggacat ccagttcgaa caatactgct 4860 cctccattat ccacaaagaa ttgatcaacc acgaaaagta caagaaccag caatccttcg 4920 atatcaactc cttggaaaac cacttgaacg atgaccaatt gatggaatcc ttgtccatct 4980 ccaaagaata cttgagattc ttcaccagga tcatctccat cattaagcaa tacccaaaga 5040 tcttgaacga aaaagagcta aaagaattga aagaaatcat cgaattgaag tacccatccg 5100 aagttcagtt gttggaattc gaagttatcg agaaggtgtc catgattatc ccaaagttgt 5160 tgttcgaaaa cgacaagcaa tcttccatga ccttgttcca agataacttg ttgaccaggt 5220 tctactccaa ttctaactct accagattct acttggaaag ggtttccgaa atggtcttgg 5280 aatctattag accaatcgtc agagaaaaga gggtgttcag aattttagag atcggtgctc 5340 gtacaggctc tttgtctaat gttgttttga ctaagttgaa cacctacttg tccaccttga 5400 attctaatgg tggttctggt tacaacatca tcattgagta caccttcacc gatatttccg 5460 ccaacttcat tattggtgaa atccaagaaa ccatgtgcaa cttgtaccca aacgttactt 5520 tcaagttctc cgtcttggac ttggagaaag agattattaa ctcctccgat ttcttgatgg 5580 gtgattacga tatagttttg atggcctacg ttatccatgc cgtttctaac attaagttct 5640 ccatcgaaca gttgtacaag ttgttgtctc caagaggttg gttgttgtgt attgaaccta 5700 agtccaacgt tgtgttctcc gatttggttt tcggttgttt taatcagtgg tggaactact 5760 acgatgatat tagaactacc cactgctcct tgtctgaatc tcaatggaat cagttgttgt 5820 tgaaccagtc cttgaacaac gaatcctctt cttcttctaa ctgttacggt ggtttctcca 5880 acgtttcttt tattggtggt gaaaaggatg tcgactccca ttctttcata ttgcactgcc 5940 aaaaagaatc catctcccaa atgaagttag ccaccactat taacaacggt ttgtcatctg 6000 gttccatcgt tatcgttttg aactctcaac aattgaccaa catgaagtcc tacccaaagg 6060 ttattgagta tattcaagag gctacctctt tgtgcaagac cattgaaatt atcgattcca 6120 aggacgtctt gaactctacc aattcagttt tggaaaagat ccaaaagtcc ttgttggtgt 6180 tctgtttgtt gggttatgac ttgttggaga acaactacca agaacagtct ttcgaatacg 6240 ttaagttgtt gaacttgatc tctactaccg cctcttcatc taatgataag aaaccaccaa 6300 aggtcttgtt gatcaccaag caatctgaaa gaatctccag gtctttctac tccagatcct 6360 tgattggtat ttccagaacc tctatgaacg agtacccaaa tttgtccatt acctctatcg 6420 atttggatac caacgactac tcattgcagt ctttgttgaa gccaatcttc agcaactcta 6480 agttttccga caacgagttc atcttcaaaa agggcttgat gttcgtgtcc aggatcttta 6540 agaacaagca gttgctagaa tcctccaacg cttttgaaac tgactcttct aacttgtact 6600 gtaaggcctc ttctgacttg tcttacaagt acgctattaa gcagtctatg ttgaccgaaa 6660 atcagatcga aatcaaggtt gaatgcgtcg gtattaactt caaggacaac ctattctaca 6720 agggcttgtt gccacaagaa attttcagaa tgggtgacat ctacaatcca ccatatggtt 6780 tggaatgctc tggtgttatt accagaattg gttctaacgt caccgaatac tcagttggtc 6840 aaaatgtttt tggtttcgcc agacattctt tgggttctca tgttgttacc aacaaggatt 6900 tggttatctt gaagccagat accatctcat tttctgaagc tgcttctatc ccagttgttt 6960 actgtactgc ttggtactcc ttgttcaaca ttggtcagtt gtctaacgaa gaatccatcc 7020 taattcattc tgctactggt ggtgtaggtt tggcttcttt gaatttgttg aaaatgaaga 7080 atcagcaaca gcaaccattg accaatgttt atgctactgt tggctctaac gagaagaaga 7140 agttcttgat cgataacttc aacaacttgt tcaaagagga cggcgaaaac attttctcta 7200 ccagagacaa agaatactcc aaccagttgg aatccaagat cgatgttatt ttgaacacct 7260 tgtccggtga attcgtcgaa tctaatttca agtccttgag atccttcggt agattgattg 7320 atttgtctgc tactcacgtt tacgccaatc aacaaattgg tctaggtaac ttcaagttcg 7380 accacttgta ttctgctgtt gacttggaaa gattgatcga cgaaaaacct aagttgttgc 7440 agtccatctt gcaaagaatt accaactcta tcgtcaacgg ttccttggaa aaaattccaa 7500 ttaccatctt cccatccacc gaaactaagg atgctatcga attattgtcc aagagatccc 7560 atatcggtaa agttgttgta gattgcaccg atatctctaa gtgtaatcct gttggtgatg 7620 tgatcaccaa cttctctatg agattgccaa agccaaacta ccagttgaat ttgaactcca 7680 ccttgttgat tactggtcag tctggtttgt ctatcccttt gttgaattgg ttgttgtcta 7740 agtctggtgg taacgttaag aacgttgtca tcatttctaa gtccaccatg aagtggaagt 7800 tgcagactat gatttcccat ttcgtttccg gtttcggtat ccattttaac tacgttcaag 7860 tcgacatctc caactacgat gctttgtctg aagctattaa gcaattgcca tctgatttgc 7920 caccaatcac ctctgttttt catttggctg ctatctacaa cgatgttcca atggatcaag 7980 ttaccatgtc taccgttgaa tctgttcata accctaaagt tttgggtgcc gttaacttgc 8040 atagaatctc tgtttctttt ggttggaagt tgaaccactt cgtcttgttc tcttctatta 8100 ctgctattac cggttaccca gaccaatcta tctacaattc tgccaactct attttggacg 8160 ctttgtccaa ctttagaagg tttatgggtt tgccatcctt ctccattaac ttgggtccaa 8220 tgaaggatga aggtaaggtt tctaccaaca agagcatcaa gaagctattc aagtctagag 8280 gtttgccaag cctatccttg aacaagttat ttggtttgtt ggaggtcgtc atcaacaacc 8340 catctaatca tgttatccca tcccaattga tttgctcccc aatcgatttc aagacctaca 8400 tcgaatcttt ctcaactatg aggccaaagt tgttacactt gcaacctacc atttccaagc 8460 agcaatcttc tatcattaac gattctacca aggcttcctc caacatttca ttgcaagata 8520 agatcacctc caaggtgtct gatttgttgt ccattccaat ctccaagatc aacttcgatc 8580 atccattgaa acactacggc ttggattctt tgttgaccgt tcaattcaaa tcctggatcg 8640 acaaagaatt cgaaaagaac ttgttcaccc atatccaatt ggccaccatc tctattaact 8700 cattcttgga aaaggtgaac ggcttgtcta caaacaataa caacaacaac aattccaacg 8760 tcaagtcctc tccatccatt gtcaaagaag aaatcgttac cttggacaag gatcaacaac 8820 cattgctatt gaaagaacac cagcacatta tcatctcccc agatattaga atcaacaagc 8880 caaagaggga atccttgatt agaaccccaa tcttgaacaa attcaaccag atcaccgaat 8940 ccattatcac tccatctaca ccatctttgt cccaatccga tgttttgaaa actccaccaa 9000 tcaagtcttt gaacaacact aagaactcca gcttgattaa caccccacca attcaatctg 9060 tccaacaaca tcaaaagcaa caacaaaagg tccaagtcat ccaacaacag caacaaccat 9120 tatccagatt gtcctacaag agcaacaaca actctttcgt tttgggtatc ggtatttctg 9180 ttccaggtga acctatttcc caacaatcct tgaaagactc catctccaat gacttttctg 9240 ataaggctga aactaacgag aaggtcaaga gaatctttga gcaatctcaa atcaagacca 9300 gacacttggt tagagattac actaagccag agaactccat caagttcaga catttggaaa 9360 ccattaccga tgtgaacaac cagttcaaga aagttgttcc agatttggct caacaagcct 9420 gtttgagagc tttgaaagat tggggtggtg ataagggtga tattacccat atagtttctg 9480 ttacctccac cggtattatc atcccagatg ttaatttcaa gttgatcgac ttgttgggct 9540 tgaacaagga tgttgaaaga gtgtctttga acctaatggg ttgtttggct ggtttgagtt 9600 ctttgagaac tgctgcttct ttggctaagg cttctccaag aaatagaatt ttggttgtct 9660 gtaccgaagt ctgctccttg catttttcta atactgatgg tggtgatcaa atggtcgcct 9720 cttctatttt tgctgatggt tctgctgctt acattattgg ttgtaaccca agaattgaag 9780 aaaccccatt atacgaagtc atgtgctcca ttaacagatc tttcccaaat accgaaaacg 9840 ccatggtttg ggatttggaa aaagaaggtt ggaacttggg tttggatgct tctattccaa 9900 ttgtcattgg ttctggtatt gaagccttcg ttgatacttt gttggataag gctaagttgc 9960 aaacttccac tgctatttct gctaaggatt gcgaattctt gattcatact ggtggcaagt 10020 ccatcttgat gaacatcgaa aattccttgg gtatcgaccc aaagcaaact aagaatactt 10080 gggatgttta ccatgcctac ggcaatatgt catctgcctc tgttattttc gttatggatc 10140 atgccagaaa gtccaagtct ttgccaactt actcaatttc tttggctttt ggtccaggtt 10200 tggcttttga aggttgtttc ttgaagaacg tcgtctgaac agaagacggg agacactagc 10260 acacaacttt accaggcaag gtatttgacg ctagcatgtg tccaattcag tgtcatttat 10320 gattttttgt agtaggatat aaatatatac agcgctccaa atagtgcggt tgccccaaaa 10380 acaccacgga acctcatctg ttctcgtact ttgttgtgac aaagtagctc actgccttat 10440 tatcacattt tcattatgca acgcttcgga aaatacgatg ttgaaaatgc ctctagagat 10500 gaaaaacaat cgtaaaaggg tcctgcgtaa ttgaaacatt tgatcagtat gcagtggcac 10560 agaaacaacc aggaatacta tagtcatagg caatacaagg tatatattgg ctatgcagac 10620 ccctccagaa agtaccgacg tcaagttaga tacacttaac gaacctagtg cacatttaat 10680 tgagaaaaat gtggctcttc ctaaggacat attccgttcg tacttgagtt attggatcta 10740 tgaaatcgct cgctatacac cagtcatgat tttgtctgag atcgacttgc atcaaccttt 10800 gaaaaatata aggatgagaa agtgaaatcg gttttttttt tccattgtcg tcatcaacat 10860 gattttttaa ataaataaat acgatttttt attttttttc ccttctttgt ttttgttttg 10920 cttattccca tcttcattat taaattcttc cgctcttaat aaaggagttt ttttattatc 10980 ttcttgtgta atcatccttt ttctttaatt ttcttccttt tctttttctc tttactggtt 11040 tttttacttc tttattctca accatctaaa gaatattatt gctttctacc aataaaatct 11100 gttaattcta tttggattgt cgtctactca agtctcgcct agtaaataaa cgataaacaa 11160 atttgaagta agaataacaa tatagggaga gaaatttttc tatttttaat ttcgaaacag 11220 gtaccaaaaa atctaagttc actttagcac tatttgggaa agcttttata taaaaaatct 11280 gaaacaaaat catatcaaag 11300 <210> 81 <211> 11140 <212> DNA <213> Artificial Sequence <220> <223> DiPKS-4 <400> 81 cggcacccac cataaagatt actttagcgt tggggttgct tttcatatga gcagcgatct 60 tcctaaccga catctctgta gaggcggtag aaacagacat cgaaacacgg agagatcgcg 120 gtacgtctgg ttggtagctc agtgacgggc acagatagcg acatttactg atacagagac 180 agttacgaaa gatggaaaca catgcagaga atgtggtcta ttccttattc ttaagatcgg 240 cgaagctaac agagttaatg ctgggccata gctggacggc agaaagcacg caggaagcaa 300 caggcgcgtt ggacttttaa ttttcgagga ccgcgaatcc ttacatcaca cccaatcccc 360 cacaagtgat cccccacaca ccatagcttc aaaatgtttc tactcctttt ttactcttcc 420 agattttctc ggactccgcg catcgccgta ccacttcaaa acacccaagc acagcatact 480 aaatttcccc tctttcttcc tctagggtgt cgttaattac ccgtactaaa ggtttggaaa 540 agaaaaaaga gaccgcctcg tttctttttc ttcgtcgaaa aaggcaataa aaatttttat 600 cacgtttctt tttcttgaaa attttttttt ttgatttttt tctctttcga tgacctccca 660 ttgatattta agttaataaa cggtcttcaa tttctcaagt ttcagtttca tttttcttgt 720 tctattacaa ctttttttac ttcttgctca ttagaaagaa agcatagcaa tctaatctaa 780 gttttaataa acaatgaaca agaactccaa aatccagtcc ccaaactctt ctgatgttgc 840 tgttattggt gttggtttta gattcccagg taactctaat gacccagaat ctttgtggaa 900 caacttgttg gatggtttcg atgctattac ccaagtccca aaagaaagat gggctacttc 960 ttttagagag atgggtttga tcaagaacaa gttcggtggt ttcttgaagg attctgaatg 1020 gaagaatttc gaccctttgt tctttggtat cggtccaaaa gaagctccat tcattgatcc 1080 acaacaaagg ttgttgttgt ccatcgtttg ggaatctttg gaagatgctt acatcagacc 1140 agatgaattg agaggttcta acactggtgt tttcatcggt gtttctaaca acgattacac 1200 caagttgggt ttccaagaca actactctat ttctccatac actatgaccg gctctaactc 1260 ttcattgaac tccaacagaa tttcctactg cttcgatttt agaggtccat ccattactgt 1320 tgataccgct tgttcttctt ccttggtttc tgttaatttg ggtgtccaat ccatccaaat 1380 gggtgaatgt aagattgcta tttgcggtgg tgttaacgct ttgtttgatc catctacatc 1440 tgttgccttt tccaagttgg gtgttttgtc tgaaaatggc agatgcaact cttttagtga 1500 tcaagcctct ggttacgtta gatctgaagg tgctggtgtt gttgttttga agtctttgga 1560 acaagctaag ttggatggtg atagaatcta cggtgttatc aagggtgttt cctctaatga 1620 agatggtgct tctaatggtg acaagaactc tttgactact ccatcttgtg aagcccaatc 1680 cattaacatt tctaaggcta tggaaaaggc ctccttgtct ccatctgata tctattacat 1740 tgaagcccat ggtactggta ctccagttgg tgatccaatt gaagttaagg ccttgtccaa 1800 gatcttctcc aactctaaca acaaccagtt gaacaacttc tctaccgatg gtaatgataa 1860 cgatgatgat gatgacgata acacctctcc agaaccatta ttgattggct cattcaagtc 1920 caacatcggt catttggaat ctgctgctgg tattgcttct ttgattaagt gttgcttgat 1980 gttgaagaac aggatgttgg ttccatccat taactgctct aatttgaacc catccattcc 2040 attcgatcag tacaacatct ccgttatcag agaaatcaga caattcccaa ccgataagtt 2100 ggttaacatc ggtatcaatt ctttcggttt cggtggttct aactgccatt tgattattca 2160 agagtacaac aacaacttca agaacaactc taccatctgc aataacaaca acaacaacaa 2220 taacaacatc gactacttga tcccaatctc ctctaagact aagaagtcct tggataagta 2280 cttgattttg atcaagacca actccaacta ccacaaggat atttctttcg atgacttcgt 2340 caagttccaa atcaagtcta agcagtacaa cttgtccaac agaatgacta ccattgctaa 2400 cgattggaac tccttcatta agggttctaa cgaattccac aacttgatcg aatctaagga 2460 tggtgaaggt ggttcttcat cttctaacag aggtattgat tccgccaatc aaatcaacac 2520 tactactacc tctaccatca acgatatcga acctttgttg gttttcgttt tctgtggtca 2580 aggtccacaa tggaatggta tgattaagac cttgtacaac tccgagaacg ttttcaagaa 2640 caccgttgat catgttgaca gcatcttgta caagtacttc ggttactcca ttttgaacgt 2700 cttgtctaag atcgatgata acgacgattc catcaaccat ccaatagttg ctcaaccatc 2760 tttgttcttg ttgcaaattg gtttggtcga gttgtttaag tactggggta tctacccatc 2820 tatctctgtt ggtcattctt tcggtgaagt ctcttcttat tacttgtccg gtatcatctc 2880 tttggaaacc gcttgtaaaa tcgtctacgt cagatcctct aatcagaaca aaactatggg 2940 ttccggtaag atgttggttg tttctatggg ttttaagcaa tggaacgatc aattctctgc 3000 tgaatggtcc gatattgaaa ttgcttgtta caacgctcca gattccatag ttgttactgg 3060 taacgaagaa agattgaaag aattgtccat caagttgtcc gacgaatcca atcaaatttt 3120 caacaccttc ttgaggtccc catgttcttt tcattcttcc catcaagaag tcatcaaggg 3180 ttctatgttc gaagagttgt ctaacttgca atctactggt gaaaccgaaa tccctttgtt 3240 ctctactgtt actggtagac aagttttgtc tggtcatgtt actgctcaac acatctacga 3300 taatgttaga gaaccagtct tgttccaaaa gacgattgaa tccattacct cctacatcaa 3360 gtctcactac ccatccaatc aaaaggttat ctacgttgaa attgctccac acccaacctt 3420 gttttcattg atcaaaaagt ccatcccatc ctccaacaag aattcctctt ctgttttgtg 3480 tccattgaac agaaaagaaa actccaacaa ctcctacaag aagttcgttt ctcagttgta 3540 cttcaacggt gttaacgttg acttcaactt ccagttgaac tccatttgcg ataacgttaa 3600 caacgatcac catttgaaca acgtcaagca aaactccttc aaagagacta ccaattcctt 3660 gccaagatac caatgggaac aagatgaata ttggtccgaa ccattgatct ccagaaagaa 3720 tagattggaa ggtccaacta cttccttgtt gggtcataga attatctaca gcttcccagt 3780 tttccaatcc gttttggact tgcaatctga caactacaaa tacttgttgg accacttggt 3840 taacggtaag ccagtttttc caggtgctgg ttatttggat atcatcatcg aattcttcga 3900 ctaccaaaag cagcagttga attcctctga ttcctctaac tcctacatca tcaacgttga 3960 caagatccaa ttcttgaacc caattcactt gaccgaaaac aagttgcaaa ccttgcaatc 4020 ttctttcgaa cctatcgtta ctaagaagtc tgccttctct gttaacttct tcatcaagga 4080 taccgtcgag gatcaatcta aggttaagtc tatgtctgac gaaacttgga ctaacacttg 4140 taaggctacc atttccttgg aacaacaaca gccatctcca tcttctactt tgactttgtc 4200 taagaagcaa gacttgcaga tcttgagaaa cagatgcgat attagcaagc tagacaagtt 4260 tgagttgtac gacaagatct ctaagaattt gggcttgcag tacaactcct tgtttcaagt 4320 tgttgatacc atcgaaactg gtaaggattg ctcttttgct actttgtctt tgccagaaga 4380 tactttgttc accaccattt tgaacccatg cttgttggat aactgtttcc atggtttgtt 4440 gaccttgatc aacgaaaagg gttctttcgt tgtcgagtcc atttcttctg tttctatcta 4500 cttggagaac atcggttcct tcaatcaaac ttctgttggt aacgtccagt tctacttgta 4560 caccactatt tctaaagcca cctcctttag ttctgaaggt acttgtaagt tgttcaccaa 4620 ggatggttcc ttgattttgt ctatcggtaa gttcatcatc aagtccacca atccaaagtc 4680 tactaagacc aacgaaacta tcgaatctcc attggacgaa accttctcta ttgaatggca 4740 atctaaggat tctccaattc caaccccaca acaaatccaa caacaatctc cattgaactc 4800 taacccatcc ttcattagat ctaccatctt gaaggacatc cagttcgaac aatactgctc 4860 ctccattatc cacaaagaat tgatcaacca cgaaaagtac aagaaccagc aatccttcga 4920 tatcaactcc ttggaaaacc acttgaacga tgaccaattg atggaatcct tgtccatctc 4980 caaagaatac ttgagattct tcaccaggat catctccatc attaagcaat acccaaagat 5040 cttgaacgaa aaagagctaa aagaattgaa agaaatcatc gaattgaagt acccatccga 5100 agttcagttg ttggaattcg aagttatcga gaaggtgtcc atgattatcc caaagttgtt 5160 gttcgaaaac gacaagcaat cttccatgac cttgttccaa gataacttgt tgaccaggtt 5220 ctactccaat tctaactcta ccagattcta cttggaaagg gtttccgaaa tggtcttgga 5280 atctattaga ccaatcgtca gagaaaagag ggtgttcaga attttagaga tcggtgctcg 5340 tacaggctct ttgtctaatg ttgttttgac taagttgaac acctacttgt ccaccttgaa 5400 ttctaatggt ggttctggtt acaacatcat cattgagtac accttcaccg atatttccgc 5460 caacttcatt attggtgaaa tccaagaaac catgtgcaac ttgtacccaa acgttacttt 5520 caagttctcc gtcttggact tggagaaaga gattattaac tcctccgatt tcttgatggg 5580 tgattacgat atagttttga tggcctacgt tatccatgcc gtttctaaca ttaagttctc 5640 catcgaacag ttgtacaagt tgttgtctcc aagaggttgg ttgttgtgta ttgaacctaa 5700 gtccaacgtt gtgttctccg atttggtttt cggttgtttt aatcagtggt ggaactacta 5760 cgatgatatt agaactaccc actgctcctt gtctgaatct caatggaatc agttgttgtt 5820 gaaccagtcc ttgaacaacg aatcctcttc ttcttctaac tgttacggtg gtttctccaa 5880 cgtttctttt attggtggtg aaaaggatgt cgactcccat tctttcatat tgcactgcca 5940 aaaagaatcc atctcccaaa tgaagttagc caccactatt aacaacggtt tgtcatctgg 6000 ttccatcgtt atcgttttga actctcaaca attgaccaac atgaagtcct acccaaaggt 6060 tattgagtat attcaagagg ctacctcttt gtgcaagacc attgaaatta tcgattccaa 6120 ggacgtcttg aactctacca attcagtttt ggaaaagatc caaaagtcct tgttggtgtt 6180 ctgtttgttg ggttatgact tgttggagaa caactaccaa gaacagtctt tcgaatacgt 6240 taagttgttg aacttgatct ctactaccgc ctcttcatct aatgataaga aaccaccaaa 6300 ggtcttgttg atcaccaagc aatctgaaag aatctccagg tctttctact ccagatcctt 6360 gattggtatt tccagaacct ctatgaacga gtacccaaat ttgtccatta cctctatcga 6420 tttggatacc aacgactact cattgcagtc tttgttgaag ccaatcttca gcaactctaa 6480 gttttccgac aacgagttca tcttcaaaaa gggcttgatg ttcgtgtcca ggatctttaa 6540 gaacaagcag ttgctagaat cctccaacgc ttttgaaact gactcttcta acttgtactg 6600 taaggcctct tctgacttgt cttacaagta cgctattaag cagtctatgt tgaccgaaaa 6660 tcagatcgaa atcaaggttg aatgcgtcgg tattaacttc aaggacaacc tattctacaa 6720 gggcttgttg ccacaagaaa ttttcagaat gggtgacatc tacaatccac catatggttt 6780 ggaatgctct ggtgttatta ccagaattgg ttctaacgtc accgaatact cagttggtca 6840 aaatgttttt ggtttcgcca gacattcttt gggttctcat gttgttacca acaaggattt 6900 ggttatcttg aagccagata ccatctcatt ttctgaagct gcttctatcc cagttgttta 6960 ctgtactgct tggtactcct tgttcaacat tggtcagttg tctaacgaag aatccatcct 7020 aattcattct gctactggtg gtgtaggttt ggcttctttg aatttgttga aaatgaagaa 7080 tcagcaacag caaccattga ccaatgttta tgctactgtt ggctctaacg agaagaagaa 7140 gttcttgatc gataacttca acaacttgtt caaagaggac ggcgaaaaca ttttctctac 7200 cagagacaaa gaatactcca accagttgga atccaagatc gatgttattt tgaacacctt 7260 gtccggtgaa ttcgtcgaat ctaatttcaa gtccttgaga tccttcggta gattgattga 7320 tttgtctgct actcacgttt acgccaatca acaaattggt ctaggtaact tcaagttcga 7380 ccacttgtat tctgctgttg acttggaaag attgatcgac gaaaaaccta agttgttgca 7440 gtccatcttg caaagaatta ccaactctat cgtcaacggt tccttggaaa aaattccaat 7500 taccatcttc ccatccaccg aaactaagga tgctatcgaa ttattgtcca agagatccca 7560 tatcggtaaa gttgttgtag attgcaccga tatctctaag tgtaatcctg ttggtgatgt 7620 gatcaccaac ttctctatga gattgccaaa gccaaactac cagttgaatt tgaactccac 7680 cttgttgatt actggtcagt ctggtttgtc tatccctttg ttgaattggt tgttgtctaa 7740 gtctggtggt aacgttaaga acgttgtcat catttctaag tccaccatga agtggaagtt 7800 gcagactatg atttcccatt tcgtttccgg tttcggtatc cattttaact acgttcaagt 7860 cgacatctcc aactacgatg ctttgtctga agctattaag caattgccat ctgatttgcc 7920 accaatcacc tctgtttttc atttggctgc tatctacaac gatgttccaa tggatcaagt 7980 taccatgtct accgttgaat ctgttcataa ccctaaagtt ttgggtgccg ttaacttgca 8040 tagaatctct gtttcttttg gttggaagtt gaaccacttc gtcttgttct cttctattac 8100 tgctattacc ggttacccag accaatctat ctacaattct gccaactcta ttttggacgc 8160 tttgtccaac tttagaaggt ttatgggttt gccatccttc tccattaact tgggtccaat 8220 gaaggatgaa ggtaaggttt ctaccaacaa gagcatcaag aagctattca agtctagagg 8280 tttgccaagc ctatccttga acaagttatt tggtttgttg gaggtcgtca tcaacaaccc 8340 atctaatcat gttatcccat cccaattgat ttgctcccca atcgatttca agacctacat 8400 cgaatctttc tcaactatga ggccaaagtt gttacacttg caacctacca tttccaagca 8460 gcaatcttct atcattaacg attctaccaa ggcttcctcc aacatttcat tgcaagataa 8520 gatcacctcc aaggtgtctg atttgttgtc cattccaatc tccaagatca acttcgatca 8580 tccattgaaa cactacggct tggattcttt gttgaccgtt caattcaaat cctggatcga 8640 caaagaattc gaaaagaact tgttcaccca tatccaattg gccaccatct ctattaactc 8700 attcttggaa aaggtgaacg gcttgtctac aaacaataac aacaacaaca attccaacgt 8760 caagtcctct ccatccattg tcaaagaaga aatcgttacc ttggacaagg atcaacaacc 8820 attgctattg aaagaacacc agcacattat catctcccca gatattagaa tcaacaagcc 8880 aaagagggaa tccttgatta gaaccccaat cttgaacaaa ttcaaccaga tcaccgaatc 8940 cattatcact ccatctacac catctttgtc ccaatccgat gttttgaaaa ctccaccaat 9000 caagtctttg aacaacacta agaactccag cttgattaac accccaccaa ttcaatctgt 9060 ccaacaacat caaaagcaac aacaaaaggt ccaagtcatc caacaacagc aacaaccatt 9120 atccagattg tcctacaaga gcaacaacaa ctctttcgtt ttgggtatcg gtatttctgt 9180 tccaggtgaa cctatttccc aacaatcctt gaaagactcc atctccaatg acttttctga 9240 taaggctgaa actaacgaga aggtcaagag aatctttgag caatctcaaa tcaagaccag 9300 acacttggtt agagattaca ctaagccaga gaactccatc aagttcagac atttggaaac 9360 cattaccgat gtgaacaacc agttcaagaa agttgttcca gatttggctc aacaagcctg 9420 tttgagagct ttgaaagatt ggggtggtga taagggtgat attacccata tagtttctgt 9480 tacctccacc ggtattatca tcccagatgt taatttcaag ttgatcgact tgttgggctt 9540 gaacaaggat gttgaaagag tgtctttgaa cctaatgggt tgtttggctg gtttgagttc 9600 tttgagaact gctgcttctt tggctaaggc ttctccaaga aatagaattt tggttgtctg 9660 taccgaagtc tgctccttgc atttttctaa tactgatggt ggtgatcaaa tggtcgcctc 9720 ttctattttt gctgatggtt ctgctgctta cattattggt tgtaacccaa gaattgaaga 9780 aaccccatta tacgaagtca tgtgctccat taacagatct ttcccaaata ccgaaaacgc 9840 catggtttgg gatttggaaa aagaaggttg gaacttgggt ttggatgctt ctattccaat 9900 tgtcattggt tctggtattg aagccttcgt tgatactttg ttggataagg ctaagttgca 9960 aacttccact gctatttctg ctaaggattg cgaattcttg attcatactg gtggcaagtc 10020 catcttgatg aacatcgaaa attccttggg tatcgaccca aagcaaacta agaatacttg 10080 ggatgtttac catgcctacg gcaatatgtc atctgcctct gttattttcg ttatggatca 10140 tgccagaaag tccaagtctt tgccaactta ctcaatttct ttggcttttg gtccaggttt 10200 ggcttttgaa ggttgtttct tgaagaacgt cgtctgaaca gaagacggga gacactagca 10260 cacaacttta ccaggcaagg tatttgacgc tagcatgtgt ccaattcagt gtcatttatg 10320 attttttgta gtaggatata aatatataca gcgctccaaa tagtgcggtt gccccaaaaa 10380 caccacggaa cctcatctgt tctcgtactt tgttgtgaca aagtagctca ctgccttatt 10440 atcacatttt cattatgcaa cgcttcggaa aatacgatgt tgaaaatgcc tctagagatg 10500 aaaaacaatc gtaaaagggt cctgcgtaat tgaaacattt gatcagtatg cagtggcaca 10560 gaaacaacca ggaatactat agtcataggc aatacaaggt atatattggc tatgcagacc 10620 cctccagaaa gtaccgacgt caagttagat acacttaacg aacctagtgc acatttaatt 10680 gagaaaaatg tggctcttcc taaggacata ttccgttcgt acttgagtta ttggatctat 10740 gaaatcgctc gctatacacc agtcatgatt ttgtcgaaga catatgccca ctttgggaaa 10800 tagaaatggt cattttaagc tcaagtgaag cgaaaaaagg aggtatactc ctttacgcgt 10860 cacccaatct ggataggcac gtcaaactca ttaggtctca tcaagaacta gtgtagaaat 10920 gacgcttgaa ctccgaactt taaacaaagt tctgtttttg tttctgtttc tgtttcctgt 10980 tgctgtctct gtttctattt ttttcgtata gctctatttc ccttgtagat aaacatatat 11040 aagaatgcta ttatagaagc gtgtattttc ctccccctag cttcaacctg taattccctt 11100 cttagtaaag cgaactagaa ccagtttaat aggatataga 11140 <210> 82 <211> 11637 <212> DNA <213> Artificial Sequence <220> <223> DiPKS-5 <400> 82 atgaacgcta atatatgggt ggctgcttca gatggtaatt tggaccgagt ggaacatatc 60 ctccgcgaga gtaaaggcgc catgaccccg caatccaagg acattaacgg ctacactcca 120 atgcatgctg ccgccgcata cggccacctg gatttgctga agaaaatgtg caatgagtac 180 aatggagaca ttaatgtgtt ggacaacgac ggcgataccc cgttgcacca tgtggaggat 240 gtggccactg ccaggttgat cgtggaagag ctgggtggag acttcactat caggaatgtg 300 gagggccaaa cgccatacga ctcgttcgtc gagaacggtg aagatggtga gctaatcgag 360 tacatgagga ttaagtccgg cgtggccgat gttcacggag tggacggcgt gcagggtgag 420 ggtgtcatcg acagcaaatt gctggaagag ttcaaggaca acgtgagata caccttggaa 480 aatgaccctg aggaaggagc cgatgaggcc actctgcaac gcaggaggca gttggaacag 540 atcattacgg gagacaacgc tgaggaggag ttggaaaggt acatccgtgc tatggtcaga 600 gagcagatgc tgggccaggg ctccatggcg ggttccgggg acgaaccaga ttccaagaga 660 agaaaataac gaaagcaaca ggcgcgttgg acttttaatt ttcgaggacc gcgaatcctt 720 acatcacacc caatccccca caagtgatcc cccacacacc atagcttcaa aatgtttcta 780 ctcctttttt actcttccag attttctcgg actccgcgca tcgccgtacc acttcaaaac 840 acccaagcac agcatactaa atttcccctc tttcttcctc tagggtgtcg ttaattaccc 900 gtactaaagg tttggaaaag aaaaaagaga ccgcctcgtt tctttttctt cgtcgaaaaa 960 ggcaataaaa atttttatca cgtttctttt tcttgaaaat tttttttttt gatttttttc 1020 tctttcgatg acctcccatt gatatttaag ttaataaacg gtcttcaatt tctcaagttt 1080 cagtttcatt tttcttgttc tattacaact ttttttactt cttgctcatt agaaagaaag 1140 catagcaatc taatctaagt tttaataaac aatgaacaag aactccaaaa tccagtcccc 1200 aaactcttct gatgttgctg ttattggtgt tggttttaga ttcccaggta actctaatga 1260 cccagaatct ttgtggaaca acttgttgga tggtttcgat gctattaccc aagtcccaaa 1320 agaaagatgg gctacttctt ttagagagat gggtttgatc aagaacaagt tcggtggttt 1380 cttgaaggat tctgaatgga agaatttcga ccctttgttc tttggtatcg gtccaaaaga 1440 agctccattc attgatccac aacaaaggtt gttgttgtcc atcgtttggg aatctttgga 1500 agatgcttac atcagaccag atgaattgag aggttctaac actggtgttt tcatcggtgt 1560 ttctaacaac gattacacca agttgggttt ccaagacaac tactctattt ctccatacac 1620 tatgaccggc tctaactctt cattgaactc caacagaatt tcctactgct tcgattttag 1680 aggtccatcc attactgttg ataccgcttg ttcttcttcc ttggtttctg ttaatttggg 1740 tgtccaatcc atccaaatgg gtgaatgtaa gattgctatt tgcggtggtg ttaacgcttt 1800 gtttgatcca tctacatctg ttgccttttc caagttgggt gttttgtctg aaaatggcag 1860 atgcaactct tttagtgatc aagcctctgg ttacgttaga tctgaaggtg ctggtgttgt 1920 tgttttgaag tctttggaac aagctaagtt ggatggtgat agaatctacg gtgttatcaa 1980 gggtgtttcc tctaatgaag atggtgcttc taatggtgac aagaactctt tgactactcc 2040 atcttgtgaa gcccaatcca ttaacatttc taaggctatg gaaaaggcct ccttgtctcc 2100 atctgatatc tattacattg aagcccatgg tactggtact ccagttggtg atccaattga 2160 agttaaggcc ttgtccaaga tcttctccaa ctctaacaac aaccagttga acaacttctc 2220 taccgatggt aatgataacg atgatgatga tgacgataac acctctccag aaccattatt 2280 gattggctca ttcaagtcca acatcggtca tttggaatct gctgctggta ttgcttcttt 2340 gattaagtgt tgcttgatgt tgaagaacag gatgttggtt ccatccatta actgctctaa 2400 tttgaaccca tccattccat tcgatcagta caacatctcc gttatcagag aaatcagaca 2460 attcccaacc gataagttgg ttaacatcgg tatcaattct ttcggtttcg gtggttctaa 2520 ctgccatttg attattcaag agtacaacaa caacttcaag aacaactcta ccatctgcaa 2580 taacaacaac aacaacaata acaacatcga ctacttgatc ccaatctcct ctaagactaa 2640 gaagtccttg gataagtact tgattttgat caagaccaac tccaactacc acaaggatat 2700 ttctttcgat gacttcgtca agttccaaat caagtctaag cagtacaact tgtccaacag 2760 aatgactacc attgctaacg attggaactc cttcattaag ggttctaacg aattccacaa 2820 cttgatcgaa tctaaggatg gtgaaggtgg ttcttcatct tctaacagag gtattgattc 2880 cgccaatcaa atcaacacta ctactacctc taccatcaac gatatcgaac ctttgttggt 2940 tttcgttttc tgtggtcaag gtccacaatg gaatggtatg attaagacct tgtacaactc 3000 cgagaacgtt ttcaagaaca ccgttgatca tgttgacagc atcttgtaca agtacttcgg 3060 ttactccatt ttgaacgtct tgtctaagat cgatgataac gacgattcca tcaaccatcc 3120 aatagttgct caaccatctt tgttcttgtt gcaaattggt ttggtcgagt tgtttaagta 3180 ctggggtatc tacccatcta tctctgttgg tcattctttc ggtgaagtct cttcttatta 3240 cttgtccggt atcatctctt tggaaaccgc ttgtaaaatc gtctacgtca gatcctctaa 3300 tcagaacaaa actatgggtt ccggtaagat gttggttgtt tctatgggtt ttaagcaatg 3360 gaacgatcaa ttctctgctg aatggtccga tattgaaatt gcttgttaca acgctccaga 3420 ttccatagtt gttactggta acgaagaaag attgaaagaa ttgtccatca agttgtccga 3480 cgaatccaat caaattttca acaccttctt gaggtcccca tgttcttttc attcttccca 3540 tcaagaagtc atcaagggtt ctatgttcga agagttgtct aacttgcaat ctactggtga 3600 aaccgaaatc cctttgttct ctactgttac tggtagacaa gttttgtctg gtcatgttac 3660 tgctcaacac atctacgata atgttagaga accagtcttg ttccaaaaga cgattgaatc 3720 cattacctcc tacatcaagt ctcactaccc atccaatcaa aaggttatct acgttgaaat 3780 tgctccacac ccaaccttgt tttcattgat caaaaagtcc atcccatcct ccaacaagaa 3840 ttcctcttct gttttgtgtc cattgaacag aaaagaaaac tccaacaact cctacaagaa 3900 gttcgtttct cagttgtact tcaacggtgt taacgttgac ttcaacttcc agttgaactc 3960 catttgcgat aacgttaaca acgatcacca tttgaacaac gtcaagcaaa actccttcaa 4020 agagactacc aattccttgc caagatacca atgggaacaa gatgaatatt ggtccgaacc 4080 attgatctcc agaaagaata gattggaagg tccaactact tccttgttgg gtcatagaat 4140 tatctacagc ttcccagttt tccaatccgt tttggacttg caatctgaca actacaaata 4200 cttgttggac cacttggtta acggtaagcc agtttttcca ggtgctggtt atttggatat 4260 catcatcgaa ttcttcgact accaaaagca gcagttgaat tcctctgatt cctctaactc 4320 ctacatcatc aacgttgaca agatccaatt cttgaaccca attcacttga ccgaaaacaa 4380 gttgcaaacc ttgcaatctt ctttcgaacc tatcgttact aagaagtctg ccttctctgt 4440 taacttcttc atcaaggata ccgtcgagga tcaatctaag gttaagtcta tgtctgacga 4500 aacttggact aacacttgta aggctaccat ttccttggaa caacaacagc catctccatc 4560 ttctactttg actttgtcta agaagcaaga cttgcagatc ttgagaaaca gatgcgatat 4620 tagcaagcta gacaagtttg agttgtacga caagatctct aagaatttgg gcttgcagta 4680 caactccttg tttcaagttg ttgataccat cgaaactggt aaggattgct cttttgctac 4740 tttgtctttg ccagaagata ctttgttcac caccattttg aacccatgct tgttggataa 4800 ctgtttccat ggtttgttga ccttgatcaa cgaaaagggt tctttcgttg tcgagtccat 4860 ttcttctgtt tctatctact tggagaacat cggttccttc aatcaaactt ctgttggtaa 4920 cgtccagttc tacttgtaca ccactatttc taaagccacc tcctttagtt ctgaaggtac 4980 ttgtaagttg ttcaccaagg atggttcctt gattttgtct atcggtaagt tcatcatcaa 5040 gtccaccaat ccaaagtcta ctaagaccaa cgaaactatc gaatctccat tggacgaaac 5100 cttctctatt gaatggcaat ctaaggattc tccaattcca accccacaac aaatccaaca 5160 acaatctcca ttgaactcta acccatcctt cattagatct accatcttga aggacatcca 5220 gttcgaacaa tactgctcct ccattatcca caaagaattg atcaaccacg aaaagtacaa 5280 gaaccagcaa tccttcgata tcaactcctt ggaaaaccac ttgaacgatg accaattgat 5340 ggaatccttg tccatctcca aagaatactt gagattcttc accaggatca tctccatcat 5400 taagcaatac ccaaagatct tgaacgaaaa agagctaaaa gaattgaaag aaatcatcga 5460 attgaagtac ccatccgaag ttcagttgtt ggaattcgaa gttatcgaga aggtgtccat 5520 gattatccca aagttgttgt tcgaaaacga caagcaatct tccatgacct tgttccaaga 5580 taacttgttg accaggttct actccaattc taactctacc agattctact tggaaagggt 5640 ttccgaaatg gtcttggaat ctattagacc aatcgtcaga gaaaagaggg tgttcagaat 5700 tttagagatc ggtgctcgta caggctcttt gtctaatgtt gttttgacta agttgaacac 5760 ctacttgtcc accttgaatt ctaatggtgg ttctggttac aacatcatca ttgagtacac 5820 cttcaccgat atttccgcca acttcattat tggtgaaatc caagaaacca tgtgcaactt 5880 gtacccaaac gttactttca agttctccgt cttggacttg gagaaagaga ttattaactc 5940 ctccgatttc ttgatgggtg attacgatat agttttgatg gcctacgtta tccatgccgt 6000 ttctaacatt aagttctcca tcgaacagtt gtacaagttg ttgtctccaa gaggttggtt 6060 gttgtgtatt gaacctaagt ccaacgttgt gttctccgat ttggttttcg gttgttttaa 6120 tcagtggtgg aactactacg atgatattag aactacccac tgctccttgt ctgaatctca 6180 atggaatcag ttgttgttga accagtcctt gaacaacgaa tcctcttctt cttctaactg 6240 ttacggtggt ttctccaacg tttcttttat tggtggtgaa aaggatgtcg actcccattc 6300 tttcatattg cactgccaaa aagaatccat ctcccaaatg aagttagcca ccactattaa 6360 caacggtttg tcatctggtt ccatcgttat cgttttgaac tctcaacaat tgaccaacat 6420 gaagtcctac ccaaaggtta ttgagtatat tcaagaggct acctctttgt gcaagaccat 6480 tgaaattatc gattccaagg acgtcttgaa ctctaccaat tcagttttgg aaaagatcca 6540 aaagtccttg ttggtgttct gtttgttggg ttatgacttg ttggagaaca actaccaaga 6600 acagtctttc gaatacgtta agttgttgaa cttgatctct actaccgcct cttcatctaa 6660 tgataagaaa ccaccaaagg tcttgttgat caccaagcaa tctgaaagaa tctccaggtc 6720 tttctactcc agatccttga ttggtatttc cagaacctct atgaacgagt acccaaattt 6780 gtccattacc tctatcgatt tggataccaa cgactactca ttgcagtctt tgttgaagcc 6840 aatcttcagc aactctaagt tttccgacaa cgagttcatc ttcaaaaagg gcttgatgtt 6900 cgtgtccagg atctttaaga acaagcagtt gctagaatcc tccaacgctt ttgaaactga 6960 ctcttctaac ttgtactgta aggcctcttc tgacttgtct tacaagtacg ctattaagca 7020 gtctatgttg accgaaaatc agatcgaaat caaggttgaa tgcgtcggta ttaacttcaa 7080 ggacaaccta ttctacaagg gcttgttgcc acaagaaatt ttcagaatgg gtgacatcta 7140 caatccacca tatggtttgg aatgctctgg tgttattacc agaattggtt ctaacgtcac 7200 cgaatactca gttggtcaaa atgtttttgg tttcgccaga cattctttgg gttctcatgt 7260 tgttaccaac aaggatttgg ttatcttgaa gccagatacc atctcatttt ctgaagctgc 7320 ttctatccca gttgtttact gtactgcttg gtactccttg ttcaacattg gtcagttgtc 7380 taacgaagaa tccatcctaa ttcattctgc tactggtggt gtaggtttgg cttctttgaa 7440 tttgttgaaa atgaagaatc agcaacagca accattgacc aatgtttatg ctactgttgg 7500 ctctaacgag aagaagaagt tcttgatcga taacttcaac aacttgttca aagaggacgg 7560 cgaaaacatt ttctctacca gagacaaaga atactccaac cagttggaat ccaagatcga 7620 tgttattttg aacaccttgt ccggtgaatt cgtcgaatct aatttcaagt ccttgagatc 7680 cttcggtaga ttgattgatt tgtctgctac tcacgtttac gccaatcaac aaattggtct 7740 aggtaacttc aagttcgacc acttgtattc tgctgttgac ttggaaagat tgatcgacga 7800 aaaacctaag ttgttgcagt ccatcttgca aagaattacc aactctatcg tcaacggttc 7860 cttggaaaaa attccaatta ccatcttccc atccaccgaa actaaggatg ctatcgaatt 7920 attgtccaag agatcccata tcggtaaagt tgttgtagat tgcaccgata tctctaagtg 7980 taatcctgtt ggtgatgtga tcaccaactt ctctatgaga ttgccaaagc caaactacca 8040 gttgaatttg aactccacct tgttgattac tggtcagtct ggtttgtcta tccctttgtt 8100 gaattggttg ttgtctaagt ctggtggtaa cgttaagaac gttgtcatca tttctaagtc 8160 caccatgaag tggaagttgc agactatgat ttcccatttc gtttccggtt tcggtatcca 8220 ttttaactac gttcaagtcg acatctccaa ctacgatgct ttgtctgaag ctattaagca 8280 attgccatct gatttgccac caatcacctc tgtttttcat ttggctgcta tctacaacga 8340 tgttccaatg gatcaagtta ccatgtctac cgttgaatct gttcataacc ctaaagtttt 8400 gggtgccgtt aacttgcata gaatctctgt ttcttttggt tggaagttga accacttcgt 8460 cttgttctct tctattactg ctattaccgg ttacccagac caatctatct acaattctgc 8520 caactctatt ttggacgctt tgtccaactt tagaaggttt atgggtttgc catccttctc 8580 cattaacttg ggtccaatga aggatgaagg taaggtttct accaacaaga gcatcaagaa 8640 gctattcaag tctagaggtt tgccaagcct atccttgaac aagttatttg gtttgttgga 8700 ggtcgtcatc aacaacccat ctaatcatgt tatcccatcc caattgattt gctccccaat 8760 cgatttcaag acctacatcg aatctttctc aactatgagg ccaaagttgt tacacttgca 8820 acctaccatt tccaagcagc aatcttctat cattaacgat tctaccaagg cttcctccaa 8880 catttcattg caagataaga tcacctccaa ggtgtctgat ttgttgtcca ttccaatctc 8940 caagatcaac ttcgatcatc cattgaaaca ctacggcttg gattctttgt tgaccgttca 9000 attcaaatcc tggatcgaca aagaattcga aaagaacttg ttcacccata tccaattggc 9060 caccatctct attaactcat tcttggaaaa ggtgaacggc ttgtctacaa acaataacaa 9120 caacaacaat tccaacgtca agtcctctcc atccattgtc aaagaagaaa tcgttacctt 9180 ggacaaggat caacaaccat tgctattgaa agaacaccag cacattatca tctccccaga 9240 tattagaatc aacaagccaa agagggaatc cttgattaga accccaatct tgaacaaatt 9300 caaccagatc accgaatcca ttatcactcc atctacacca tctttgtccc aatccgatgt 9360 tttgaaaact ccaccaatca agtctttgaa caacactaag aactccagct tgattaacac 9420 cccaccaatt caatctgtcc aacaacatca aaagcaacaa caaaaggtcc aagtcatcca 9480 acaacagcaa caaccattat ccagattgtc ctacaagagc aacaacaact ctttcgtttt 9540 gggtatcggt atttctgttc caggtgaacc tatttcccaa caatccttga aagactccat 9600 ctccaatgac ttttctgata aggctgaaac taacgagaag gtcaagagaa tctttgagca 9660 atctcaaatc aagaccagac acttggttag agattacact aagccagaga actccatcaa 9720 gttcagacat ttggaaacca ttaccgatgt gaacaaccag ttcaagaaag ttgttccaga 9780 tttggctcaa caagcctgtt tgagagcttt gaaagattgg ggtggtgata agggtgatat 9840 tacccatata gtttctgtta cctccaccgg tattatcatc ccagatgtta atttcaagtt 9900 gatcgacttg ttgggcttga acaaggatgt tgaaagagtg tctttgaacc taatgggttg 9960 tttggctggt ttgagttctt tgagaactgc tgcttctttg gctaaggctt ctccaagaaa 10020 tagaattttg gttgtctgta ccgaagtctg ctccttgcat ttttctaata ctgatggtgg 10080 tgatcaaatg gtcgcctctt ctatttttgc tgatggttct gctgcttaca ttattggttg 10140 taacccaaga attgaagaaa ccccattata cgaagtcatg tgctccatta acagatcttt 10200 cccaaatacc gaaaacgcca tggtttggga tttggaaaaa gaaggttgga acttgggttt 10260 ggatgcttct attccaattg tcattggttc tggtattgaa gccttcgttg atactttgtt 10320 ggataaggct aagttgcaaa cttccactgc tatttctgct aaggattgcg aattcttgat 10380 tcatactggt ggcaagtcca tcttgatgaa catcgaaaat tccttgggta tcgacccaaa 10440 gcaaactaag aatacttggg atgtttacca tgcctacggc aatatgtcat ctgcctctgt 10500 tattttcgtt atggatcatg ccagaaagtc caagtctttg ccaacttact caatttcttt 10560 ggcttttggt ccaggtttgg cttttgaagg ttgtttcttg aagaacgtcg tctgaacaga 10620 agacgggaga cactagcaca caactttacc aggcaaggta tttgacgcta gcatgtgtcc 10680 aattcagtgt catttatgat tttttgtagt aggatataaa tatatacagc gctccaaata 10740 gtgcggttgc cccaaaaaca ccacggaacc tcatctgttc tcgtactttg ttgtgacaaa 10800 gtagctcact gccttattat cacattttca ttatgcaacg cttcggaaaa tacgatgttg 10860 aaaatgcctc tagagatgaa aaacaatcgt aaaagggtcc tgcgtaattg aaacatttga 10920 tcagtatgca gtggcacaga aacaaccagg aatactatag tcataggcaa tacaaggtat 10980 atattggcta tgcagacccc tccagaaagt accgacgtca agttagatac acttaacgaa 11040 cctagtgcac atttaattga gaaaaatgtg gctcttccta aggacatatt ccgttcgtac 11100 ttgagttatt ggatctatga aatcgctcgc tatacaccag tcatgatttt gtctaataga 11160 cgttcttaca aggtaaaatt tcaccgcgtt tttaaataga atgaaaaaaa cgttgtagag 11220 tgaaagaaaa gcaacaaata tacagttcac aaggcagctt cgtatagtaa tacagcacga 11280 aaaacagctc atagaaatgg taacacagac caatccggtc cctgttacat atccaacgga 11340 tgcttatatc cccacgtatc tgcccgatga taaggtctcc aatctggcag atttgaaaaa 11400 attgatagaa atggattcca gactagattt gtatctgaca agaaggaggc tggatacgtc 11460 catcaattta cctacaaaca ccaagaccaa ggaccatccc cccaataaag agatgctgag 11520 gatttacgtc tacaacacta cggaaagcag ccctcgcagc gattctggca ccccagcgga 11580 ctcaggcaag actacatgga cactgagaat agaaggtaag cttctgcacg agtccgc 11637 <210> 83 <211> 7114 <212> DNA <213> Artificial Sequence <220> <223> PDH <400> 83 caccggagct tggatatgat aaacgaaata ttcttgaatc gtgagatcgc ctgttttcaa 60 aaccgttgga ggcagaaaca attttgtcac aagatgggca ttctacccca tccttgctgt 120 attattgtag tctcgctttc ttttatgctg gacaaatgag actactgcac atttttatac 180 gttcttggtt ttttttaaag gtgtggtttc ggcattatcc tgccgcacgt ttcttggata 240 attcatcctg attctctatt ttaaacgctt cagcctatca ggatttggtt ttgatacata 300 ctgcaagagt gtatctcggg aacagtcatt tattccgcaa caaacttaat tgcggaacgc 360 gttaggcgat ttctagcata tatcaaatac cgttcgcgat ttcttctggg ttcgtctctt 420 ttcttttaaa tacttattaa cgtactcaaa caactacact tcgttgtatc tcagaatgag 480 atccctcagt atgacaatac atcattctaa acgttcgtaa aacacatatg aaacaacttt 540 ataacaaagc gaacaaaatg ggcaacatga gatgaaactc cgcgtccctt agctgaacta 600 cccaaacgta cgaatgcctg aacaattagt ttagatccga gattccgcgc ttccatcatt 660 tagtataatc catattttat ataatatata ggataagtaa cagcccgcga aaaacaacaa 720 ataatcataa aaattttaga actagacata tcgagtttat cattatcaat actgccattt 780 caaagaatac gtaaataatt aatagtagtg attttcctaa ctttatttag tcaaaaaatt 840 agccttttaa ttctgctgta acccgtacat gcccaaaata gggggcgggt tacacagaat 900 atataacatc gtaggtgtct gggtgaacag tttattcctg gcatccacta aatataatgg 960 agcccgcttt ttaagctggc atccagaaaa aaaaagaatc ccagcaccaa aatattgttt 1020 tcttcaccaa ccatcagttc ataggtccat tctcttagcg caactacaga gaacaggggc 1080 acaaacaggc aaaaaacggg cacaacctca atggagtgat gcaacctgcc tggagtaaat 1140 gatgacacaa ggcaattgac ccacgcatgt atctatctca ttttcttaca ccttctatta 1200 ccttctgctc tctctgattt ggaaaaagct gaaaaaaaag gttgaaacca gttccctgaa 1260 attattcccc tacttgacta ataagtatat aaagacggta ggtattgatt gtaattctgt 1320 aaatctattt cttaaacttc ttaaattcta cttttatagt tagtcttttt tttagtttta 1380 aaacaccaag aacttagttt cgactagaaa atttattata aaaggaagag aaataattaa 1440 acaatgacta agctacactt tgacactgct gaaccagtca agatcacact tccaaatggt 1500 ttgacatacg agcaaccaac cggtctattc attaacaaca agtttatgaa agctcaagac 1560 ggtaagacct atcccgtcga agatccttcc actgaaaaca ccgtttgtga ggtctcttct 1620 gccaccactg aagatgttga atatgctatc gaatgtgccg accgtgcttt ccacgacact 1680 gaatgggcta cccaagaccc aagagaaaga ggccgtctac taagtaagtt ggctgacgaa 1740 ttggaaagcc aaattgactt ggtttcttcc attgaagctt tggacaatgg taaaactttg 1800 gccttagccc gtggggatgt taccattgca atcaactgtc taagagatgc tgctgcctat 1860 gccgacaaag tcaacggtag aacaatcaac accggtgacg gctacatgaa cttcaccacc 1920 ttagagccaa tcggtgtctg tggtcaaatt attccatgga actttccaat aatgatgttg 1980 gcttggaaga tcgccccagc attggccatg ggtaacgtct gtatcttgaa acccgctgct 2040 gtcacacctt taaatgccct atactttgct tctttatgta agaaggttgg tattccagct 2100 ggtgtcgtca acatcgttcc aggtcctggt agaactgttg gtgctgcttt gaccaacgac 2160 ccaagaatca gaaagctggc ttttaccggt tctacagaag tcggtaagag tgttgctgtc 2220 gactcttctg aatctaactt gaagaaaatc actttggaac taggtggtaa gtccgcccat 2280 ttggtctttg acgatgctaa cattaagaag actttaccaa atctagtaaa cggtattttc 2340 aagaacgctg gtcaaatttg ttcctctggt tctagaattt acgttcaaga aggtatttac 2400 gacgaactat tggctgcttt caaggcttac ttggaaaccg aaatcaaagt tggtaatcca 2460 tttgacaagg ctaacttcca aggtgctatc actaaccgtc aacaattcga cacaattatg 2520 aactacatcg atatcggtaa gaaagaaggc gccaagatct taactggtgg cgaaaaagtt 2580 ggtgacaagg gttacttcat cagaccaacc gttttctacg atgttaatga agacatgaga 2640 attgttaagg aagaaatttt tggaccagtt gtcactgtcg caaagttcaa gactttagaa 2700 gaaggtgtcg aaatggctaa cagctctgaa ttcggtctag gttctatggg tatcgaaaca 2760 gaatctttga gcacaggttt gaaggtggcc aagatgttga aggccggtac cgtctggatc 2820 aacacataca acgattttga ctccagagtt ccattcggtg gtgttaagca atctggttac 2880 ggtagagaaa tgggtgaaga agtctaccat gcatacactg aagtaaaagc tgtcagaatt 2940 aagttgtaaa gacataaaac tgaaacaaca ccaattaata atagactttt ggacttcttc 3000 gccagaggtt tggtcaagtc tccaatcaag gttgtcggct tgtctacctt gccagaaatt 3060 tacgaaaaga tggaaaaggg tcaaatcgtt ggtagatacg ttgttgacac ttctaaataa 3120 gcgaatttct tatgatttat gatttttatt attaaataag ttataaaaaa aataagtgta 3180 tacaaatttt aaagtgactc ttaggtttta aaacgaaaat tcttattctt gagtaactct 3240 ttcctgtagg tcaggttgct ttctcaggta tagcatgagg tcgctcttat tgaccacacc 3300 tctaccggca tggcttaaat aacatactca tcactaaaca ttcttaacaa tcaaagcaac 3360 aggcgcgttg gacttttaat tttcgaggac cgcgaatcct tacatcacac ccaatccccc 3420 acaagtgatc ccccacacac catagcttca aaatgtttct actccttttt tactcttcca 3480 gattttctcg gactccgcgc atcgccgtac cacttcaaaa cacccaagca cagcatacta 3540 aatttcccct ctttcttcct ctagggtgtc gttaattacc cgtactaaag gtttggaaaa 3600 gaaaaaagag accgcctcgt ttctttttct tcgtcgaaaa aggcaataaa aatttttatc 3660 acgtttcttt ttcttgaaaa tttttttttt tgattttttt ctctttcgat gacctcccat 3720 tgatatttaa gttaataaac ggtcttcaat ttctcaagtt tcagtttcat ttttcttgtt 3780 ctattacaac tttttttact tcttgctcat tagaaagaaa gcatagcaat ctaatctaag 3840 ttttaataca tctaccagtc aacagccaac aattaactaa ttaaacaatg tcccaaactc 3900 ataagcacgc tattccagct aatattgctg atagatgctt gatcaaccca gaacagtacg 3960 aaactaagta caagcaatcc atcaacgatc cagatacttt ttggggtgaa caaggtaaga 4020 ttttggattg gattacccca taccaaaagg tcaagaatac ttcttttgct ccaggcaacg 4080 tttccattaa gtggtatgaa gatggtactt tgaacttggc tgctaactgt ttggatagac 4140 acttgcaaga aaacggtgat agaaccgcta ttatttggga aggtgatgat acctcccaat 4200 ccaaacatat ctcttacaga gaattgcaca gagatgtctg tagattcgct aacactttgt 4260 tggatttggg catcaaaaag ggtgatgttg ttgctatcta tatgccaatg gttcctgaag 4320 ctgctgttgc tatgttggct tgtgctagaa ttggtgctgt tcattctgtt attttcggtg 4380 gtttttcacc agaagctgtt gccggtagaa ttatcgattc ttcatccaga ttggttatca 4440 ccgctgatga aggtgttaga gctggtagat ctattccatt gaaaaagaac gttgatgacg 4500 ccttgaagaa cccaaatgtt acttctgttg aacacgtcat cgttttgaag agaactggtt 4560 ctgatatcga ttggcaagag ggtagagatt tgtggtggag agatttgatt gaaaaggctt 4620 ctccagaaca tcaaccagaa gctatgaacg ctgaagatcc tttgtttatc ttgtacactt 4680 ctggttctac tggtaagcca aaaggtgttt tacacactac tggtggttat ttggtttacg 4740 ctgctactac tttcaagtac gttttcgatt atcacccagg tgatatctat tggtgtactg 4800 ctgatgttgg ttgggttact ggtcattctt atttgttgta tggtccattg gcttgtggtg 4860 ctactacatt gatgtttgaa ggtgttccaa attggccaac tccagctaga atgtgtcaag 4920 ttgttgacaa acaccaagtc aacatcttgt atactgctcc aactgctatt agagctttga 4980 tggctgaagg tgataaggct attgaaggta ctgatagatc ctccttgaga atcttgggtt 5040 ctgttggtga acctattaac cctgaagcct gggaatggta ttggaagaaa attggtaaag 5100 aaaagtgccc agttgttgat acttggtggc aaactgaaac tggtggtttt atgattactc 5160 cattgccagg tgctattgaa ttgaaagctg gttctgctac tagaccattt tttggtgttc 5220 aaccagcttt ggttgataac gaaggtcatc cacaagaagg tgctactgaa ggtaatttgg 5280 ttattactga ttcttggcca ggtcaagcta gaactttgtt tggtgatcac gaaagattcg 5340 aacagactta cttctctacc ttcaagaaca tgtacttctc tggtgatggt gctagaagag 5400 atgaagatgg ttactattgg attaccggta gagttgatga tgtcttgaat gtttctggtc 5460 acagattagg tactgccgaa attgaatctg ctttggttgc tcatccaaag attgctgaag 5520 ctgcagttgt tggtattcca catgctatta agggtcaagc tatctacgct tacgttactt 5580 tgaatcatgg tgaagaacca tctccagaat tatacgctga agttagaaac tgggtcagaa 5640 aagaaattgg tccattagct accccagatg ttttacattg gactgattct ttgccaaaga 5700 ccagatcagg taagatcatg agaagaatct tgagaaagat tgctgctggt gatacttcta 5760 acttgggtga tacttcaaca ttagctgatc caggtgttgt tgaaaagcct ttggaagaaa 5820 aacaagctat tgccatgcca tcctaataat taaatactat tttcaaaatt ctacttaaaa 5880 ataacagaag acgggagaca ctagcacaca actttaccag gcaaggtatt tgacgctagc 5940 atgtgtccaa ttcagtgtca tttatgattt tttgtagtag gatataaata tatacagcgc 6000 tccaaatagt gcggttgccc caaaaacacc acggaacctc atctgttctc gtactttgtt 6060 gtgacaaagt agctcactgc cttattatca cattttcatt atgcaacgct tcggaaaata 6120 cgatgttgaa aatgcctcta gagatgaaaa acaatcgtaa aagggtcctg cgtaattgaa 6180 acatttgatc agtatgcagt ggcacagaaa caaccaggaa tactatagtc ataggcaata 6240 caaggtatat attggctatg cagacccctc cagaaagtac cgacgtcaag ttagatacac 6300 ttaacgaacc tagtgcacat ttaattgaga aaaatgtggc tcttcctaag gacatattcc 6360 gttcgtactt gagttattgg atctatgaaa tcgctcgcta tacaccagtc atgattttgt 6420 cattgcgaag actatactga tatatgaatt taaactagag cggaccaact atcatccgct 6480 aattactgac attaccaaat gagatctgtg aatgggcaag ataaaaaaca aaaattgaaa 6540 tgtttgacgt tatgtaaaac tattaattcc ttcgctttcg gcggtcacag aatttgcgtg 6600 tagctgactc ttgttcaatc aatatcattt gttactttat ttgaaagtct gtattactgc 6660 gcctattgtc atccgtacca aagaacgtca aaaagaaaca agataatttt tgtgcttaca 6720 ccatttatag atcactgagc ccagaatatc gctggagctc agtgtaagtg gcatgaacac 6780 aactctgact gatcgcacat attgccgtta tcataaatac tagttgtact tgtcaatgcg 6840 acgaatggca tcatgcctat tattacgttc ctctttttcc gtttcatgtt tccagaatgc 6900 tattgaatct aacacttcaa ttataaaaaa gaataaatcc gcaataattt taggctaatt 6960 gttgtactgt caagcgaacc taatggttaa aattcagagg aaccttcgac gtagtctgat 7020 cgctacttct atatcttatg ttcccagtca atcaaaagtt gatactataa tagctgccat 7080 ttatacctgt tagttatggc gatcgtttat cacg 7114 <210> 84 <211> 3256 <212> DNA <213> Artificial Sequence <220> <223> Maf1 <400> 84 aatgatttaa gcgtgcgtga agataacact acaatccatt ttaaagcaac atccacattg 60 agtgtataca ccacaaaggt tttttcaggg cgtttttctc gccactttat gttgaccaaa 120 attattaatg gaacttacaa cgtttccaaa agttagttaa atacatacgt ctatttacta 180 agcaagaaat atatcatgac aagcccaaat attatattgt tatgtttaca aaaaaaaaat 240 ggctatatac atcaagtctg gaggcttttt ataacaagca agtggggtaa cttagacata 300 agattgactt ctttgaattc aacaaaaata catacttttg atgatttcaa tggtagaagc 360 ataaacaaca aataatcata aaaattttag aactagacat aaagcaacag gcgcgttgga 420 cttttaattt tcgaggaccg cgaatcctta catcacaccc aatcccccac aagtgatccc 480 ccacacacca tagcttcaaa atgtttctac tcctttttta ctcttccaga ttttctcgga 540 ctccgcgcat cgccgtacca cttcaaaaca cccaagcaca gcatactaaa tttcccctct 600 ttcttcctct agggtgtcgt taattacccg tactaaaggt ttggaaaaga aaaaagagac 660 cgcctcgttt ctttttcttc gtcgaaaaag gcaataaaaa tttttatcac gtttcttttt 720 cttgaaaatt tttttttttg atttttttct ctttcgatga cctcccattg atatttaagt 780 taataaacgg tcttcaattt ctcaagtttc agtttcattt ttcttgttct attacaactt 840 tttttacttc ttgctcatta gaaagaaagc atagcaatct aatctaagtt ttaatctaga 900 aaatttatta taaaaggaag agaaataatt aaacaatgaa atttattgat gagctagata 960 tagagagagt gaatcaaact ctcaatttcg agacaaatga ctgtaaaatc gtgggcagtt 1020 gcgatatttt cacaacaaag gcggttgcat cagatagaaa attatataaa actattgatc 1080 agcatttgga tactatttta caggaaaatg agaattacaa tgctaccctt cagcaacagc 1140 tagctgctcc cgaaacaaac caatcaccct gctcgtcgcc attttattct aataggaggg 1200 atagcaactc tttttgggag caaaagagaa gaatatcttt tagtgaatac aatagcaata 1260 ataacactaa caacagtaat ggcaatagca gtaataacaa taactattct ggacctaatg 1320 gttcttctcc agcaactttt cccaaaagtg ccaagctaaa tgaccaaaat ttaaaagaat 1380 tagtctcgaa ttacgattct ggctctatga gctcatcgtc tcttgattct tcttctaaga 1440 atgatgagag gataagaaga aggagcagta gcagtattag cagtttcaaa agtggtaaat 1500 catcgaacaa taattacagt tctggtacag caaccaacaa tgttaacaaa agaagaaaat 1560 cttcgataaa cgaaaggcca agcaatttaa gtttgggtcc gtttggtccc ataaacgaac 1620 cgtcaagccg caaaatattt gcttatctga ttgctatcct caacgcttct tatcctgacc 1680 atgatttttc atcggttgag ccaacggatt ttgtcaaaac atcattgaaa acttttattt 1740 ccaaatttga aaacacctta tattctcttg gtagacaacc agaggaatgg gtctgggagg 1800 taattaattc tcacatgact ctttctgatt gcgtcctttt tcaatattca ccttcaaact 1860 cttttttgga agatgagcct ggctatcttt ggaatcttat aggttttctt tacaacagga 1920 aaaggaaaag agtggcttac ctttacttga tttgctcgcg tctaaattcg agtacaggcg 1980 aagtggaaga tgccttggca aaaaaacctc agggaaagct tataatagat gatggctcaa 2040 atgaatacga aggagaatac gatttcactt atgatgagaa tgtaatagat gataaatcag 2100 atcaagaaga atccctacag tagagacata aaactgaaac aacaccaatt aataatagac 2160 tttacagaag acgggagaca ctagcacaca actttaccag gcaaggtatt tgacgctagc 2220 atgtgtccaa ttcagtgtca tttatgattt tttgtagtag gatataaata tatacagcgc 2280 tccaaatagt gcggttgccc caaaaacacc acggaacctc atctgttctc gtactttgtt 2340 gtgacaaagt agctcactgc cttattatca cattttcatt atgcaacgct tcggaaaata 2400 cgatgttgaa aatgcctcta gagatgaaaa acaatcgtaa aagggtcctg cgtaattgaa 2460 acatttgatc agtatgcagt ggcacagaaa caaccaggaa tactatagtc ataggcaata 2520 caaggtatat attggctatg cagacccctc cagaaagtac cgacgtcaag ttagatacac 2580 ttaacgaacc tagtgcacat ttaattgaga aaaatgtggc tcttcctaag gacatattcc 2640 gttcgtactt gagttattgg atctatgaaa tcgctcgcta tacaccagtc atgattttgt 2700 ccttaaataa catactcatc actaaacatt cttaacaatc agaaaacaac gcgtcatgaa 2760 aaagagttac tgaaccttca gatcctactt attgtaatgc ttcgcgacat ccaatccatt 2820 taataatcaa tttaaaacta gagttggtag agttccttgt tgaacgtgat aacccaaaag 2880 cataatacga gtaatgtttc agtattgcta ttatatgttt acacaaggaa aacatataat 2940 aacaaacctc taatccggta gtacttaaga aactatagtt tctatgtaca aaaaggtaac 3000 tatgtaattc ttacatttac ataacatata gaagggtcca ataaacttac taaacttact 3060 accttgttgt atataggcta gatcgtaatc cactacgtca acataaaaaa aacttaagga 3120 gtttgaattt tatgtacaaa cagattgtta aaatataata taagattatg gaaacgaact 3180 tgctctaaaa aaaatttaaa gttttataaa atcctcgcac tatcgctgtt atacatgatg 3240 tccccaaagc gtgtac 3256 <210> 85 <211> 4538 <212> DNA <213> Artificial Sequence <220> <223> Erg20K197E <400> 85 ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc acaaaaatcg 60 acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg cgtttccccc 120 tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat acctgtccgc 180 ctttctccct tcgggaagcg tggcgctttc tcaatgctca cgctgtaggt atctcagttc 240 ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc agcccgaccg 300 ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg acttatcgcc 360 actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg gtgctacaga 420 gttcttgaag tggtggccta actacggcta cactagaagg acagtatttg gtatctgcgc 480 tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg gcaaacaaac 540 caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca gaaaaaaagg 600 atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga acgaaaactc 660 acgttaaggg attttggtca tgaacgcatc tacgactgtg ggtcccgtgg agaaatgtat 720 gaaaccctgt atggagagtg attagcttgc ctcgtccccg ccgggtcacc cggccagcga 780 catggaggcc cagaataccc tccttgacag tcttgacgtg cgcagctcag gggcatgatg 840 tgactgtcgc ccgtacattt agcccataca tccccatgta taatcatttg catccataca 900 ttttgatggc cgcacggcgc gaagcaaaaa ttacggctcc tcgctgcaga cctgcgagca 960 gggaaacgct cccctcacag acgcgttgaa ttgtccccac gccgcgcccc tgtagagaaa 1020 tataaaaggt taggatttgc cactgaggtt cttctttcat atacttcctt ttaaaatctt 1080 gctaggatac agttctcaca tcacatccga acataaacaa ccatgggtaa ggaaaagact 1140 cacgtttcga ggccgcgatt aaattccaac atggatgctg atttatatgg gtataaatgg 1200 gctcgcgata atgtcgggca atcaggtgcg acaatctatc gattgtatgg gaagcccgat 1260 gcgccagagt tgtttctgaa acatggcaaa ggtagcgttg ccaatgatgt tacagatgag 1320 atggtcagac taaactggct gacggaattt atgcctcttc cgaccatcaa gcattttatc 1380 cgtactcctg atgatgcatg gttactcacc actgcgatcc ccggcaaaac agcattccag 1440 gtattagaag aatatcctga ttcaggtgaa aatattgttg atgcgctggc agtgttcctg 1500 cgccggttgc attcgattcc tgtttgtaat tgtcctttta acagcgatcg cgtatttcgt 1560 ctcgctcagg cgcaatcacg aatgaataac ggtttggttg atgcgagtga ttttgatgac 1620 gagcgtaatg gctggcctgt tgaacaagtc tggaaagaaa tgcataagct tttgccattc 1680 tcaccggatt cagtcgtcac tcatggtgat ttctcacttg ataaccttat ttttgacgag 1740 gggaaattaa taggttgtat tgatgttgga cgagtcggaa tcgcagaccg ataccaggat 1800 cttgccatcc tatggaactg cctcggtgag ttttctcctt cattacagaa acggcttttt 1860 caaaaatatg gtattgataa tcctgatatg aataaattgc agtttcattt gatgctcgat 1920 gagtttttct aatcagtact gacaataaaa agattcttgt tttcaagaac ttgtcatttg 1980 tatagttttt ttatattgta gttgttctat tttaatcaaa tgttagcgtg atttatattt 2040 tttttcgcct cgacatcatc tgcccagatg cgaagttaag tgcgcagaaa gtaatatcat 2100 gcgtcaatcg tatgtgaatg ctggtcgcta tactgctgtc gattcgatac taacgccgcc 2160 atccagtgtc gaaaacgagc tctcgagaac ccttaatcat acgttgaaac tacggcaaag 2220 gattggtcag atcgcttcat acaggggtat cccggcataa ccctcactaa agggaacaaa 2280 agctggagct cgtttaaaag caacaggcgc gttggacttt taattttcga ggaccgcgaa 2340 tccttacatc acacccaatc ccccacaagt gatcccccac acaccatagc ttcaaaatgt 2400 ttctactcct tttttactct tccagatttt ctcggactcc gcgcatcgcc gtaccacttc 2460 aaaacaccca agcacagcat actaaatttc ccctctttct tcctctaggg tgtcgttaat 2520 tacccgtact aaaggtttgg aaaagaaaaa agagaccgcc tcgtttcttt ttcttcgtcg 2580 aaaaaggcaa taaaaatttt tatcacgttt ctttttcttg aaaatttttt tttttgattt 2640 ttttctcttt cgatgacctc ccattgatat ttaagttaat aaacggtctt caatttctca 2700 agtttcagtt tcatttttct tgttctatta caactttttt tacttcttgc tcattagaaa 2760 gaaagcatag caatctaatc taagttttaa tggcgggggt cggaatgatt aaagaaaggg 2820 gctgtgggcg agattgaaac aatggcttca gaaaaagaaa ttaggagaga gagattcttg 2880 aacgttttcc ctaaattagt agaggaattg aacgcatcgc ttttggctta cggtatgcct 2940 aaggaagcat gtgactggta tgcccactca ttgaactaca acactccagg cggtaagcta 3000 aatagaggtt tgtccgttgt ggacacgtat gctattctct ccaacaagac cgttgaacaa 3060 ttggggcaag aagaatacga aaaggttgcc attctaggtt ggtgcattga gttgttgcag 3120 gcttacttct tggtcgccga tgatatgatg gacaagtcca ttaccagaag aggccaacca 3180 tgttggtaca aggttcctga agttggggaa attgccatca atgacgcatt catgttagag 3240 gctgctatct acaagctttt gaaatctcac ttcagaaacg aaaaatacta catagatatc 3300 accgaattgt tccatgaggt caccttccaa accgaattgg gccaattgat ggacttaatc 3360 actgcacctg aagacaaagt cgacttgagt aagttctccc taaagaagca ctccttcata 3420 gttactttcg agactgctta ctattctttc tacttgcctg tcgcattggc catgtacgtt 3480 gccggtatca cggatgaaaa ggatttgaaa caagccagag atgtcttgat tccattgggt 3540 gaatacttcc aaattcaaga tgactactta gactgcttcg gtaccccaga acagatcggt 3600 aagatcggta cagatatcca agataacaaa tgttcttggg taatcaacaa ggcattggaa 3660 cttgcttccg cagaacaaag aaagacttta gacgaaaatt acggtaagaa ggactcagtc 3720 gcagaagcca aatgcaaaaa gattttcaat gacttgaaaa ttgaacagct ataccacgaa 3780 tatgaagagt ctattgccaa ggatttgaag gccaaaattt ctcaggtcga tgagtctcgt 3840 ggcttcaaag ctgatgtctt aactgcgttc ttgaacaaag tttacaagag aagcaaataa 3900 ccagttaata aaccgtggca aacatgatgg tggcctaatg gaggtcacca acagaagacg 3960 ggagacacta gcacacaact ttaccaggca aggtatttga cgctagcatg tgtccaattc 4020 agtgtcattt atgatttttt gtagtaggat ataaatatat acagcgctcc aaatagtgcg 4080 gttgccccaa aaacaccacg gaacctcatc tgttctcgta ctttgttgtg acaaagtagc 4140 tcactgcctt attatcacat tttcattatg caacgcttcg gaaaatacga tgttgaaaat 4200 gcctctagag atgaaaaaca atcgtaaaag ggtcctgcgt aattgaaaca tttgatcagt 4260 atgcagtggc acagaaacaa ccaggaatac tatagtcata ggcaatacaa ggtatatatt 4320 ggctatgcag acccctccag aaagtaccga cgtcaagtta gatacactta acgaacctag 4380 tgcacattta attgagaaaa atgtggctct tcctaaggac atattccgtt cgtacttgag 4440 ttattggatc tatgaaatcg ctcgctatac accagtcatg attttgtcgc ggccgcggta 4500 cctaataact tcgtatagca tacattatac gaagttat 4538 <210> 86 <211> 3503 <212> DNA <213> Artificial Sequence <220> <223> Erg1p:UB14-Erg20:deg <400> 86 tgtgcacaaa ggccataata ttatgtctac agaatatact agatgtcctc cctataggat 60 atagtaatcc tctaaatgga accgatattt ctacataata atattacgat tattcctcct 120 tccgttttat atgtttcatt atcctagcac actatcaatc tttgcatttc agcttccatt 180 agatttgatg actatttctc aatctttatg ttatctcctt acgccgcatg tgataatata 240 ctgctagtat gactactagt tgatagaaga tagttgattt ttactccaac aaaagtaaca 300 atattattta gaactataga ttccattttg tgcattccca tattctcgag gaaaactttt 360 agtatattct gtagacataa tattatcgcc tttgtgaaca atagaatccc aacaattgtc 420 gcaaatttac caattttcta gattgcagtc accttttcaa ttaatcacta gtgtttcact 480 tgtaacattg tcgttgttgt ttaacgtatt ctgtcccgtg ccaactatga caaaaatgca 540 atgatttcag cggttaaata cgaagcgcaa caagagttag cgaaaaataa gtaccaccat 600 tctacgctac cattacttac tgaaattaga gacaactgtt atctattggc agatgttcat 660 acggggcttt caaatattga tgaaattatg tgatgtttag aagaagattc gaactgtttt 720 cagtagattt ggtaactgtg caaccataac tcatgcctac gttcgggatt taatcttctc 780 gcagtctgca ggcgccttga gatttgcgtt cggcctaaac gtttgctcca caaacgtgaa 840 tggtatgaac atggacatga gcgtggttca gggcactcta cgggatcgtg gcgaatggga 900 atcgttctgc aagctcttct accaaaccat cggcgaattt gcgtcgcttt aatgcgatac 960 tgccgtagcg ggccttcgta tagctcggcc gagctcgtac aaaaggcaag cagtgtatcg 1020 gacagagctg atataacaca atacgctcgt agtcgatgca tgccgtggct gctctcggtc 1080 gggtataagt cttagacaat agtcttacct cgcatgtata ataaatcttt tgtatttaat 1140 ctattatatg tttctatgct tttttttcct attgttgttt gcttttcctt ttccttattt 1200 ctttctagct tctaattttc tttctttttt tttttttttt cattgaaaat tatatatata 1260 tatatatatc agaacaattg tccagtattg aacaatacag gttatttcga acaattgaaa 1320 aaaaaaaatc acagaaaaac atatcgagaa aagggtcaaa acaatgcaga ttttcgtcaa 1380 gactttgacc ggtaaaacca taacattgga agttgaatct tccgatacca tcgacaacgt 1440 taagtcgaaa attcaagaca aggaaggtat ccctccagat caacaaagat tgatctttgc 1500 cggtaagcag ctagaagacg gtagaacgct gtctgattac aacattcaga aggagtccac 1560 cttacatctt gtgctaaggc taagaggtgg tttccacaaa tctggtgctt ggttgttgcc 1620 agtttctttg gttaagggtt ctggtgcttc agaaaaagaa attaggagag agagattctt 1680 gaacgttttc cctaaattag tagaggaatt gaacgcatcg cttttggctt acggtatgcc 1740 taaggaagca tgtgactggt atgcccactc attgaactac aacactccag gcggtaagct 1800 aaatagaggt ttgtccgttg tggacacgta tgctattctc tccaacaaga ccgttgaaca 1860 attggggcaa gaagaatacg aaaaggttgc cattctaggt tggtgcattg agttgttgca 1920 ggcttacttc ttggtcgccg atgatatgat ggacaagtcc attaccagaa gaggccaacc 1980 atgttggtac aaggttcctg aagttgggga aattgccatc aatgacgcat tcatgttaga 2040 ggctgctatc tacaagcttt tgaaatctca cttcagaaac gaaaaatact acatagatat 2100 caccgaattg ttccatgagg tcaccttcca aaccgaattg ggccaattga tggacttaat 2160 cactgcacct gaagacaaag tcgacttgag taagttctcc ctaaagaagc actccttcat 2220 agttactttc aagactgctt actattcttt ctacttgcct gtcgcattgg ccatgtacgt 2280 tgccggtatc acggatgaaa aggatttgaa acaagccaga gatgtcttga ttccattggg 2340 tgaatacttc caaattcaag atgactactt agactgcttc ggtaccccag aacagatcgg 2400 taagatcggt acagatatcc aagataacaa atgttcttgg gtaatcaaca aggcattgga 2460 acttgcttcc gcagaacaaa gaaagacttt agacgaaaat tacggtaaga aggactcagt 2520 cgcagaagcc aaatgcaaaa agattttcaa tgacttgaaa attgaacagc tataccacga 2580 atatgaagag tctattgcca aggatttgaa ggccaaaatt tctcaggtcg atgagtctcg 2640 tggcttcaaa gctgatgtct taactgcgtt cttgaacaaa gtttacaaga gaagcaaata 2700 gtggacttct tcgccagagg tttggtcaag tctccaatca aggttgtcgg cttgtctacc 2760 ttgccagaaa tttacgaaaa gatggaaaag ggtcaaatcg ttggtagata cgttgttgac 2820 acttctaaat aagcgaattt cttatgattt atgattttta ttattaaata agttataaaa 2880 aaaataagtg tatacaaatt ttaaagtgac tcttaggttt taaaacgaaa attcttattc 2940 ttgagtaact ctttcctgta ggtcaggttg ctttctcagg tatagcatga ggtcgctctt 3000 attgaccaca cctctaccgg catggaatcg tccccaacaa aagtgggctc tcaaaattca 3060 tcacatttaa atgcatatag gaagagcaac agttggtttg catctgatgt tccttaaaga 3120 tttcgacata atgtgcgaag tagataaaat gggtcattta ttaatagtta tttcattatt 3180 aaccagttgt ggtacaaatg caactaaaga aaaaaactac taaactatcc gggaaatgcg 3240 ccttagattg cacttcttaa ttcttatttt cgatttttat ttttcctttg ataatcataa 3300 agagaaacga cgatcatttc taaagccatt tctgctagta taccgttaaa taagaaaaat 3360 aaagccaaat attataattt ttctaatgtg aatccataaa tatcaaagca tgcaaaaagg 3420 gaaagaagta atgtcttgga tttatatagc gtatttgtct aaggggagcc agctttggcg 3480 cgcctatcga gagaccgatt aca 3503 <210> 87 <211> 4859 <212> DNA <213> Artificial Sequence <220> <223> tHMGr-IDI <400> 87 ggcgcgcccg agatctttgt gttcggttac ccggctcaga tcctaacttc gtatgtttat 60 tcgtataagt tactgttgtc cacaggcaat actctgcaga aaattaaaac ggcattaatg 120 ctaggacaac cagaattgtt actactgtat gtgcgatagt tgataactgc aacattatgc 180 ccggtatatt ctcaaaaaac cctattactg catacgaaga aatcgctcga gtttatcatt 240 atcaatactg ccatttcaaa gaatacgtaa ataattaata gtagtgattt tcctaacttt 300 atttagtcaa aaaattagcc ttttaattct gctgtaaccc gtacatgccc aaaatagggg 360 gcgggttaca cagaatatat aacatcgtag gtgtctgggt gaacagttta ttcctggcat 420 ccactaaata taatggagcc cgctttttaa gctggcatcc agaaaaaaaa agaatcccag 480 caccaaaata ttgttttctt caccaaccat cagttcatag gtccattctc ttagcgcaac 540 tacagagaac aggggcacaa acaggcaaaa aacgggcaca acctcaatgg agtgatgcaa 600 cctgcctgga gtaaatgatg acacaaggca attgacccac gcatgtatct atctcatttt 660 cttacacctt ctattacctt ctgctctctc tgatttggaa aaagctgaaa aaaaaggttg 720 aaaccagttc cctgaaatta ttcccctact tgactaataa gtatataaag acggtaggta 780 ttgattgtaa ttctgtaaat ctatttctta aacttcttaa attctacttt tatagttagt 840 ctttttttta gttttaaaac accaagaact tagtttcgaa aacaatggtt ttaaccaata 900 aaacagtcat ttctggatcg aaagtcaaaa gtttatcatc tgcgcaatcg agctcatcag 960 gaccttcatc atctagtgag gaagatgatt cccgcgatat tgaaagcttg gataagaaaa 1020 tacgtccttt agaagaatta gaagcattat taagtagtgg aaatacaaaa caattgaaga 1080 acaaagaggt cgctgccttg gttattcacg gtaagttacc tttgtacgct ttggagaaaa 1140 aattaggtga tactacgaga gcggttgcgg tacgtaggaa ggctctttca attttggcag 1200 aagctcctgt attagcatct gatcgtttac catataaaaa ttatgactac gaccgcgtat 1260 ttggcgcttg ttgtgaaaat gttataggtt acatgccttt gcccgttggt gttataggcc 1320 ccttggttat cgatggtaca tcttatcata taccaatggc aactacagag ggttgtttgg 1380 tagcttctgc catgcgtggc tgtaaggcaa tcaatgctgg cggtggtgca acaactgttt 1440 taactaagga tggtatgaca agaggcccag tagtccgttt cccaactttg aaaagatctg 1500 gtgcctgtaa gatatggtta gactcagaag agggacaaaa cgcaattaaa aaagctttta 1560 actctacatc aagatttgca cgtctgcaac atattcaaac ttgtctagca ggagatttac 1620 tcttcatgag atttagaaca actactggtg acgcaatggg tatgaatatg atttctaaag 1680 gtgtcgaata ctcattaaag caaatggtag aagagtatgg ctgggaagat atggaggttg 1740 tctccgtttc tggtaactac tgtaccgaca aaaaaccagc tgccatcaac tggatcgaag 1800 gtcgtggtaa gagtgtcgtc gcagaagcta ctattcctgg tgatgttgtc agaaaagtgt 1860 taaaaagtga tgtttccgca ttggttgagt tgaacattgc taagaatttg gttggatctg 1920 caatggctgg gtctgttggt ggatttaacg cacatgcagc taatttagtg acagctgttt 1980 tcttggcatt aggacaagat cctgcacaaa atgttgaaag ttccaactgt ataacattga 2040 tgaaagaagt ggacggtgat ttgagaattt ccgtatccat gccatccatc gaagtaggta 2100 ccatcggtgg tggtactgtt ctagaaccac aaggtgccat gttggactta ttaggtgtaa 2160 gaggcccgca tgctaccgct cctggtacca acgcacgtca attagcaaga atagttgcct 2220 gtgccgtctt ggcaggtgaa ttatccttat gtgctgccct agcagccggc catttggttc 2280 aaagtcatat gacccacaac aggaaacctg ctgaaccaac aaaacctaac aatttggacg 2340 ccactgatat aaatcgtttg aaagatgggt ccgtcacctg cattaaatcc taatggactt 2400 cttcgccaga ggtttggtca agtctccaat caaggttgtc ggcttgtcta ccttgccaga 2460 aatttacgaa aagatggaaa agggtcaaat cgttggtaga tacgttgttg acacttctaa 2520 ataagcgaat ttcttatgat ttatgatttt tattattaaa taagttataa aaaaaataag 2580 tgtatacaaa ttttaaagtg actcttaggt tttaaaacga aaattcttat tcttgagtaa 2640 ctctttcctg taggtcaggt tgctttctca ggtatagcat gaggtcgctc ttattgacca 2700 cacctctacc ggcatgcaag caacaggcgc gttggacttt taattttcga ggaccgcgaa 2760 tccttacatc acacccaatc ccccacaagt gatcccccac acaccatagc ttcaaaatgt 2820 ttctactcct tttttactct tccagatttt ctcggactcc gcgcatcgcc gtaccacttc 2880 aaaacaccca agcacagcat actaaatttc ccctctttct tcctctaggg tgtcgttaat 2940 tacccgtact aaaggtttgg aaaagaaaaa agagaccgcc tcgtttcttt ttcttcgtcg 3000 aaaaaggcaa taaaaatttt tatcacgttt ctttttcttg aaaatttttt tttttgattt 3060 ttttctcttt cgatgacctc ccattgatat ttaagttaat aaacggtctt caatttctca 3120 agtttcagtt tcatttttct tgttctatta caactttttt tacttcttgc tcattagaaa 3180 gaaagcatag caatctaatc taagttttaa taaacaatga ctgccgacaa caatagtatg 3240 ccccatggtg cagtatctag ttacgccaaa ttagtgcaaa accaaacacc tgaagacatt 3300 ttggaagagt ttcctgaaat tattccatta caacaaagac ctaatacccg atctagtgag 3360 acgtcaaatg acgaaagcgg agaaacatgt ttttctggtc atgatgagga gcaaattaag 3420 ttaatgaatg aaaattgtat tgttttggat tgggacgata atgctattgg tgccggtacc 3480 aagaaagttt gtcatttaat ggaaaatatt gaaaagggtt tactacatcg tgcattctcc 3540 gtctttattt tcaatgaaca aggtgaatta cttttacaac aaagagccac tgaaaaaata 3600 actttccctg atctttggac taacacatgc tgctctcatc cactatgtat tgatgacgaa 3660 ttaggtttga agggtaagct agacgataag attaagggcg ctattactgc ggcggtgaga 3720 aaactagatc atgaattagg tattccagaa gatgaaacta agacaagggg taagtttcac 3780 tttttaaaca gaatccatta catggcacca agcaatgaac catggggtga acatgaaatt 3840 gattacatcc tattttataa gatcaacgct aaagaaaact tgactgtcaa cccaaacgtc 3900 aatgaagtta gagacttcaa atgggtttca ccaaatgatt tgaaaactat gtttgctgac 3960 ccaagttaca agtttacgcc ttggtttaag attatttgcg agaattactt attcaactgg 4020 tgggagcaat tagatgacct ttctgaagtg gaaaatgaca ggcaaattca tagaatgcta 4080 taaacagaag acgggagaca ctagcacaca actttaccag gcaaggtatt tgacgctagc 4140 atgtgtccaa ttcagtgtca tttatgattt tttgtagtag gatataaata tatacagcgc 4200 tccaaatagt gcggttgccc caaaaacacc acggaacctc atctgttctc gtactttgtt 4260 gtgacaaagt agctcactgc cttattatca cattttcatt atgcaacgct tcggaaaata 4320 cgatgttgaa aatgcctcta gagatgaaaa acaatcgtaa aagggtcctg cgtaattgaa 4380 acatttgatc agtatgcagt ggcacagaaa caaccaggaa tactatagtc ataggcaata 4440 caaggtatat attggctatg cagacccctc cagaaagtac cgacgtcaag ttagatacac 4500 ttaacgaacc tagtgcacat ttaattgaga aaaatgtggc tcttcctaag gacatattcc 4560 gttcgtactt gagttattgg atctatgaaa tcgctcgcta tacaccagtc atgattttgt 4620 cacactcgta tatgcatgtt gttgaaactc tgttacgctg aactaacaat cacacatgta 4680 gaggtcaccg ggaaaagttg cgaccccatg gaaggtcgat ctcttcgttt ggctttgctt 4740 ggctggcggc attgcgcttc ttcgcttata cccgtctctt gacgctcgag ctcgttcatt 4800 gagatacctt tattcttgca cattttctgg cttttttcgc tactcgggta cggcgcgcc 4859 <210> 88 <211> 7673 <212> DNA <213> Artificial Sequence <220> <223> PGK1p:ACC1S659A,S1157A <400> 88 caagtcgcag tcgaaattca accgctcatt gccactctct ctactgcttg gtgaactagg 60 ctatacgctc aatcagcgcc aagatatata agaagaacag cactcccagt cgtattctgg 120 cacagtatag cctagcacaa tcactgtcac aattgttatc ggttctacaa ttgttctgct 180 ctcttcaatt ttcctttcct tattctactc tttttatccc tacgcacaga tattataaca 240 tctgcataat aggcatttgc aagaattact cgtgagtaag gaaagagtga ggaactatcg 300 catacctgca tttaaagatg ccgatttggg cgcgaatcct ttattttggc ttcaccctca 360 tactattatc agggccagaa aaaggaagtg tttccctcct tcttgaattg atgttaccct 420 cataaagcac gtggcctctt atcgagaaag aaattaccgt cgctcgtgat ttgtttgcaa 480 aaagaacaaa actgaaaaaa cccagacacg ctcgacttcc tgtcttccta ttgattgcag 540 cttccaattt cgtcacacaa caaggtccta gcgacggctc acaggttttg taacaagcaa 600 tcgaaggttc tggaatggcg ggaaagggtt tagtaccaca tgctatgatg cccactgtga 660 tctccagagc aaagttcgtt cgatcgtact gttactctct ctctttcaaa cagaattgtc 720 cgaatcgtgt gacaacaaca gcctgttctc acacactctt ttcttctaac caagggggtg 780 gtttagttta gtagaacctc gtgaaactta catttacata tatataaact tgcataaatt 840 ggtcaatgca agaaatacat atttggtctt ttctaattcg tagtttttca agttcttaga 900 tgctttcttt ttctcttttt tacagatcat caaggaagta attatctact ttttacaaca 960 aatataaaac aatgagcgaa gaaagcttat tcgagtcttc tccacagaag atggagtacg 1020 aaattacaaa ctactcagaa agacatacag aacttccagg tcatttcatt ggcctcaata 1080 cagtagataa actagaggag tccccgttaa gggactttgt taagagtcac ggtggtcaca 1140 cggtcatatc caagatcctg atagcaaata atggtattgc cgccgtgaaa gaaattagat 1200 ccgtcagaaa atgggcatac gagacgttcg gcgatgacag aaccgtccaa ttcgtcgcca 1260 tggccacccc agaagatctg gaggccaacg cagaatatat ccgtatggcc gatcaataca 1320 ttgaagtgcc aggtggtact aataataaca actacgctaa cgtagacttg atcgtagaca 1380 tcgccgaaag agcagacgta gacgccgtat gggctggctg gggtcacgcc tccgagaatc 1440 cactattgcc tgaaaaattg tcccagtcta agaggaaagt catctttatt gggcctccag 1500 gtaacgccat gaggtcttta ggtgataaaa tctcctctac cattgtcgct caaagtgcta 1560 aagtcccatg tattccatgg tctggtaccg gtgttgacac cgttcacgtg gacgagaaaa 1620 ccggtctggt ctctgtcgac gatgacatct atcaaaaggg ttgttgtacc tctcctgaag 1680 atggtttaca aaaggccaag cgtattggtt ttcctgtcat gattaaggca tccgaaggtg 1740 gtggtggtaa aggtatcaga caagttgaac gtgaagaaga tttcatcgct ttataccacc 1800 aggcagccaa cgaaattcca ggctccccca ttttcatcat gaagttggcc ggtagagcgc 1860 gtcacttgga agttcaactg ctagcagatc agtacggtac aaatatttcc ttgttcggta 1920 gagactgttc cgttcagaga cgtcatcaaa aaattatcga agaagcacca gttacaattg 1980 ccaaggctga aacatttcac gagatggaaa aggctgccgt cagactgggg aaactagtcg 2040 gttatgtctc tgccggtacc gtggagtatc tatattctca tgatgatgga aaattctact 2100 ttttagaatt gaacccaaga ttacaagtcg agcatccaac aacggaaatg gtctccggtg 2160 ttaacttacc tgcagctcaa ttacaaatcg ctatgggtat ccctatgcat agaataagtg 2220 acattagaac tttatatggt atgaatcctc attctgcctc agaaatcgat ttcgaattca 2280 aaactcaaga tgccaccaag aaacaaagaa gacctattcc aaagggtcat tgtaccgctt 2340 gtcgtatcac atcagaagat ccaaacgatg gattcaagcc atcgggtggt actttgcatg 2400 aactaaactt ccgttcttcc tctaatgttt ggggttactt ctccgtgggt aacaatggta 2460 atattcactc cttttcggac tctcagttcg gccatatttt tgcttttggt gaaaatagac 2520 aagcttccag gaaacacatg gttgttgccc tgaaggaatt gtccattagg ggtgatttca 2580 gaactactgt ggaatacttg atcaaacttt tggaaactga agatttcgag gataacacta 2640 ttaccaccgg ttggttggac gatttgatta ctcataaaat gaccgctgaa aagcctgatc 2700 caactcttgc cgtcatttgc ggtgccgcta caaaggcttt cttagcatct gaagaagccc 2760 gccacaagta tatcgaatcc ttacaaaagg gacaagttct atctaaagac ctactgcaaa 2820 ctatgttccc tgtagatttt atccatgagg gtaaaagata caagttcacc gtagctaaat 2880 ccggtaatga ccgttacaca ttatttatca atggttctaa atgtgatatc atactgcgtc 2940 aactatctga tggtggtctt ttgattgcca taggcggtaa atcgcatacc atctattgga 3000 aagaagaagt tgctgctaca agattatccg ttgactctat gactactttg ttggaagttg 3060 aaaacgatcc aacccagttg cgtactccat cccctggtaa attggttaaa ttcttggtgg 3120 aaaatggtga acacattatc aagggccaac catatgcaga aattgaagtt atgaaaatgc 3180 aaatgccttt ggtttctcaa gaaaatggta tcgtccagtt attaaagcaa cctggttcta 3240 ccattgttgc aggtgatatc atggctatta tgactcttga cgatccatcc aaggtcaagc 3300 acgctctacc atttgaaggt atgctgccag attttggttc tccagttatc gaaggaacca 3360 aacctgccta taaattcaag tcattagtgt ctactttgga aaacattttg aagggttatg 3420 acaaccaagt tattatgaac gcttccttgc aacaattgat agaggttttg agaaatccaa 3480 aactgcctta ctcagaatgg aaactacaca tctctgcttt acattcaaga ttgcctgcta 3540 agctagatga acaaatggaa gagttagttg cacgttcttt gagacgtggt gctgttttcc 3600 cagctagaca attaagtaaa ttgattgata tggccgtgaa gaatcctgaa tacaaccccg 3660 acaaattgct gggcgccgtc gtggaaccat tggcggatat tgctcataag tactctaacg 3720 ggttagaagc ccatgaacat tctatatttg tccatttctt ggaagaatat tacgaagttg 3780 aaaagttatt caatggtcca aatgttcgtg aggaaaatat cattctgaaa ttgcgtgatg 3840 aaaaccctaa agatctagat aaagttgcgc taactgtttt gtctcattcg aaagtttcag 3900 cgaagaataa cctgatccta gctatcttga aacattatca accattgtgc aagttatctt 3960 ctaaagtttc tgccattttc tctactcctc tacaacatat tgttgaacta gaatctaagg 4020 ctaccgctaa ggtcgctcta caagcaagag aaattttgat tcaaggcgct ttaccttcgg 4080 tcaaggaaag aactgaacaa attgaacata tcttaaaatc ctctgttgtg aaggttgcct 4140 atggctcatc caatccaaag cgctctgaac cagatttgaa tatcttgaag gacttgatcg 4200 attctaatta cgttgtgttc gatgttttac ttcaattcct aacccatcaa gacccagttg 4260 tgactgctgc agctgctcaa gtctatattc gtcgtgctta tcgtgcttac accataggag 4320 atattagagt tcacgaaggt gtcacagttc caattgttga atggaaattc caactacctt 4380 cagctgcgtt ctccaccttt ccaactgtta aatctaaaat gggtatgaac agggctgttt 4440 ctgtttcaga tttgtcatat gttgcaaaca gtcagtcatc tccgttaaga gaaggtattt 4500 tgatggctgt ggatcattta gatgatgttg atgaaatttt gtcacaaagt ttggaagtta 4560 ttcctcgtca ccaatcttct tctaacggac ctgctcctga tcgttctggt agctccgcat 4620 cgttgagtaa tgttgctaat gtttgtgttg cttctacaga aggtttcgaa tctgaagagg 4680 aaattttggt aaggttgaga gaaattttgg atttgaataa gcaggaatta atcaatgctt 4740 ctatccgtcg tatcacattt atgttcggtt ttaaagatgg gtcttatcca aagtattata 4800 cttttaacgg tccaaattat aacgaaaatg aaacaattcg tcacattgag ccggctttgg 4860 ccttccaact ggaattagga agattgtcca acttcaacat taaaccaatt ttcactgata 4920 atagaaacat ccatgtctac gaagctgtta gtaagacttc tccattggat aagagattct 4980 ttacaagagg tattattaga acgggtcata tccgtgatga catttctatt caagaatatc 5040 tgacttctga agctaacaga ttgatgagtg atatattgga taatttagaa gtcaccgaca 5100 cttcaaattc tgatttgaat catatcttca tcaacttcat tgcggtgttt gatatctctc 5160 cagaagatgt cgaagccgcc ttcggtggtt tcttagaaag atttggtaag agattgttga 5220 gattgcgtgt ttcttctgcc gaaattagaa tcatcatcaa agatcctcaa acaggtgccc 5280 cagtaccatt gcgtgccttg atcaataacg tttctggtta tgttatcaaa acagaaatgt 5340 acaccgaagt caagaacgca aaaggtgaat gggtatttaa gtctttgggt aaacctggat 5400 ccatgcattt aagacctatt gctactcctt accctgttaa ggaatggttg caaccaaaac 5460 gttataaggc acacttgatg ggtaccacat atgtctatga cttcccagaa ttattccgcc 5520 aagcatcgtc atcccaatgg aaaaatttct ctgcagatgt taagttaaca gatgatttct 5580 ttatttccaa cgagttgatt gaagatgaaa acggcgaatt aactgaggtg gaaagagaac 5640 ctggtgccaa cgctattggt atggttgcct ttaagattac tgtaaagact cctgaatatc 5700 caagaggccg tcaatttgtt gttgttgcta acgatatcac attcaagatc ggttcctttg 5760 gtccacaaga agacgaattc ttcaataagg ttactgaata tgctagaaag cgtggtatcc 5820 caagaattta cttggctgca aactcaggtg ccagaattgg tatggctgaa gagattgttc 5880 cactatttca agttgcatgg aatgatgctg ccaatccgga caagggcttc caatacttat 5940 acttaacaag tgaaggtatg gaaactttaa agaaatttga caaagaaaat tctgttctca 6000 ctgaacgtac tgttataaac ggtgaagaaa gatttgtcat caagacaatt attggttctg 6060 aagatgggtt aggtgtcgaa tgtctacgtg gatctggttt aattgctggt gcaacgtcaa 6120 gggcttacca cgatatcttc actatcacct tagtcacttg tagatccgtc ggtatcggtg 6180 cttatttggt tcgtttgggt caaagagcta ttcaggtcga aggccagcca attattttaa 6240 ctggtgctcc tgcaatcaac aaaatgctgg gtagagaagt ttatacttct aacttacaat 6300 tgggtggtac tcaaatcatg tataacaacg gtgtttcaca tttgactgct gttgacgatt 6360 tagctggtgt agagaagatt gttgaatgga tgtcttatgt tccagccaag cgtaatatgc 6420 cagttcctat cttggaaact aaagacacat gggatagacc agttgatttc actccaacta 6480 atgatgaaac ttacgatgta agatggatga ttgaaggtcg tgagactgaa agtggatttg 6540 aatatggttt gtttgataaa gggtctttct ttgaaacttt gtcaggatgg gccaaaggtg 6600 ttgtcgttgg tagagcccgt cttggtggta ttccactggg tgttattggt gttgaaacaa 6660 gaactgtcga gaacttgatt cctgctgatc cagctaatcc aaatagtgct gaaacattaa 6720 ttcaagaacc tggtcaagtt tggcatccaa actccgcctt caagactgct caagctatca 6780 atgactttaa caacggtgaa caattgccaa tgatgatttt ggccaactgg agaggtttct 6840 ctggtggtca acgtgatatg ttcaacgaag tcttgaagta tggttcgttt attgttgacg 6900 cattggtgga ttacaaacaa ccaattatta tctatatccc acctaccggt gaactaagag 6960 gtggttcatg ggttgttgtc gatccaacta tcaacgctga ccaaatggaa atgtatgccg 7020 acgtcaacgc tagagctggt gttttggaac cacaaggtat ggttggtatc aagttccgta 7080 gagaaaaatt gctggacacc atgaacagat tggatgacaa gtacagagaa ttgagatctc 7140 aattatccaa caagagtttg gctccagaag tacatcagca aatatccaag caattagctg 7200 atcgtgagag agaactattg ccaatttacg gacaaatcag tcttcaattt gctgatttgc 7260 acgataggtc ttcacgtatg gtggccaagg gtgttatttc taaggaactg gaatggaccg 7320 aggcacgtcg tttcttcttc tggagattga gaagaagatt gaacgaagaa tatttgatta 7380 aaaggttgag ccatcaggta ggcgaagcat caagattaga aaagatcgca agaattagat 7440 cgtggtaccc tgcttcagtg gaccatgaag atgataggca agtcgcaaca tggattgaag 7500 aaaactacaa aactttggac gataaactaa agggtttgaa attagagtca ttcgctcaag 7560 acttagctaa aaagatcaga agcgaccatg acaatgctat tgatggatta tctgaagtta 7620 tcaagatgtt atctaccgat gataaagaaa aattgttgaa gactttgaaa taa 7673 <210> 89 <211> 4707 <212> DNA <213> Artificial Sequence <220> <223> PT254-R2S <400> 89 agtatgacaa gttttaatcg agatagtttg acgttcgttt tttactttga atatactcgt 60 agtcttttta ctttttgagt ataaaaaaaa aatgactagc aaaataaaat tagtagtcta 120 aaaaagaaag ctcgcactca ggatcgaact aaggaccaac agatttgcaa tctgctgcgc 180 taccactgcg ccatacgagc ttttgaatta tggtaatttt gattatccta gaatgttata 240 tctcaatatc tcaatatatt ttggacatct atgaaacacc cataaagcag ccgctaccaa 300 acagacaaga ttcagtatgt aaggtaaata cctttttgca cagttaaact acccaaactt 360 attaaagctt gataaattac tgaaattcca cctttcagtt agattcaggc ctcatataga 420 ttagatatag ggtacgtaac attctgtcaa ccaagttgtt ggaatgaaag tctaaaatgt 480 catctattcg gtagcactca tgttactagt atactgtcac atgcggtgta acgtggggac 540 ataaaacaga catcaaatat aatggaagct gaaatgcaaa gatcgataat gtaataggaa 600 tgaaacatat aaaacgaaag gagaagtaat ggtaatatta gtatgtagaa ataccgattc 660 aattttgggg attcttatat tctcgagaga atttctagta taatctgtat acataatatt 720 ataggcttta ccaacaatgg aatttcgaca attatcatat tattcaccaa ttaatcacaa 780 gttggtaatg agtttgataa caagttactt tcttaacaac gttagtatcg tcaaaacact 840 cggttttact cgagcttgta gcacaataat accgtgtaga gttctgtatt gttcttctta 900 gtgcttgtat atgctcatcc cgaccttcca ttatgctggt ctcttcgccc gagaacctca 960 gttacttttc cttatgcgca tagacataca agtggacaga tgatgggtac gggcctctaa 1020 tacatccaac actctacgcc ctcttcaaga gctagaaggg caccctgcag ttggaaaggg 1080 aattatttcg taaggcgagc ccataccgtc attcatgcgg aagagttaac acgattggaa 1140 gtaggaatag tttcgaacca cggttactaa tcctaataac ggaacgctgt ctgaaggatg 1200 agtgtcagcg agtgtaactc gatgagctac ccagtagtcg tactggtcga gacaaccctt 1260 gccaacaggg agttcttcag agacatggag gctcaaaacg aaattattga cagcctagac 1320 atcaatagtc atacaacaga aagcgaccac ccaactttgg ctgataatag cgtataaaca 1380 atgcatactt tgtacgttca aaatacaatg cagtagatat atttatgcat attacatata 1440 atacatatca cataggaagc aacaggcgcg ttggactttt aattttcgag gaccgcgaat 1500 ccttacatca cacccaatcc cccacaagtg atcccccaca caccatagct tcaaaatgtt 1560 tctactcctt ttttactctt ccagattttc tcggactccg cgcatcgccg taccacttca 1620 aaacacccaa gcacagcata ctaaatttcc cctctttctt cctctagggt gtcgttaatt 1680 acccgtacta aaggtttgga aaagaaaaaa gacaccgcct cgtttctttt tcttcgtcga 1740 aaaaggcaat aaaaattttt atcacgtttc tttttcttga aaattttttt ttttgatttt 1800 tttctctttc gatgacctcc cattgatatt taagttaata aacggtcatc aatttctcaa 1860 gtttcagttt catttttctt gttctattac aacttttttt acttcttgct cattagaaag 1920 aaagcatagc aatctaatct aagttttaat tacaaaatga gagccggttc cgatcaaatt 1980 gaaggttctc cacatcatga atccgataac tctattgcca ccaagatttt gaacttcggt 2040 catacttgtt ggaagttgca aagaccatat gttgtcaagg gtatgatttc tattgcttgc 2100 ggtttgtttg gtcgtgagtt gtttaacaac agacacttgt tttcttgggg cttgatgtgg 2160 aaagcttttt ttgctttggt tcccatcctg tcctttaatt tctttgccgc cattatgaac 2220 cagatctacg atgttgatat cgacagaatc aacaagccag atttgccatt ggtttctggt 2280 gaaatgtcta ttgaaaccgc ctggattttg tccattatcg ttgctttgac tggtttgatc 2340 gttaccatca agttgaaatc tgctcccttg ttcgttttca tctacatctt tggtattttc 2400 gctggtttcg cttattccgt tccaccaatt agatggaaac aatacccatt caccaatttc 2460 ttgatcacca tctcttctca tgttggtttg gctttcactt cttactctgc tactacttct 2520 gctttgggtt taccatttgt ttggaggcca gctttctctt tcattattgc tttcatgacc 2580 gttatgggta tgaccattgc tttcgctaag gatatctctg atattgaagg tgatgctaag 2640 tacggtgttt ctactgttgc tacaaaattg ggtgctagaa acatgacctt tgttgtctct 2700 ggtgttctgt tgttgaacta cttggtttcc atttccattg gtatcatttg gccacaggtt 2760 ttcaagtcca acatcatgat tttgtctcat gccatcttgg ctttctgctt gatttttcaa 2820 actagagaat tggccttggc taactatgct tctgctccat ctagacaatt cttcgaattc 2880 atctggttgt tgtactacgc cgaatacttc gtctacgtgt tcattctcga gcatgcatct 2940 agagggccgc atcatgtaat tagttatgtc acgcttacat tcacgccctc cccccacatc 3000 cgctctaacc gaaaaggaag gagttagaca acctgaagtc taggtcccta tttatttttt 3060 tatagttatg ttagtattaa gaacgttatt tatatttcaa atttttcttt tttttctgta 3120 cagacgcgtg tacgcatgta acattatact gaaaaccttg cttgagaagg ttttgggacg 3180 ctcgaaggct ttaatttgcc cagctctaat gcactcaatc ccgaggcctg acgcgacata 3240 tcagcttaga ctagggcggg ggtgttgacg tttggggttg aataaatcta ttgtactaat 3300 cggcttcaac gtgccccacg ggtggcacct caggaggggc ccacagcgag gaagtaaact 3360 gttattcgtc ggcgatggtg gtagctaatt atgttccttg ccactacaat agtatctaag 3420 ccgtgtaatg ggaacatcca cactttagtg aatcgatgtg cagcttcaga ataccattcc 3480 ttgaagccgt gtccataaac aatatcgaga gaccgattac actcgagcat gcatctagag 3540 ggccgcatca tgtaattagt tatgtcacgc ttacattcac gccctccccc cacatccgct 3600 ctaaccgaaa aggaaggagt tagacaacct gaagtctagg tccctattta tttttttata 3660 gttatgttag tattaagaac gttatttata tttcaaattt ttcttttttt tctgtacaga 3720 cgcgtgtacg catgtaacat tatactgaaa accttgcttg agaaggtttt gggacgctcg 3780 aaggctttaa tttgctttgc gaaaccctat gctctgttgt tcggatttga aattttaaaa 3840 ctacattaat gtgttagttt ttctttcttt ctttctttgt cttgacgtga tttggacttc 3900 tgtcttgcat tcgcgtccat tcatctgacc caatattcct tttggttttg ttatccttat 3960 aaaaagaaag gaagcttctt agagggaaaa aaatgatgaa gagtaatgcc aaaatataaa 4020 taaataaata aatatgaaaa tcattttcta tttttaatag aataagaaga gcatcttaag 4080 attacaattt caagaaatag tttacacagt atatccaata actccaataa actactttcc 4140 tatacaaatt tctatggtgg gattaatagt aaaacttctg tacttctcta attcaccaag 4200 aaattaaggt aaacatctgg taagcactat ccagcttttt gctattacac atatggcttt 4260 tctgcaatca tttcttccca ttttgtctca agccgttagt cttgaaacca caggcggagt 4320 agagttactt gatgcggtat tttacatgcc ttttttcact gcaaaaaaaa tgaaatacat 4380 atttacacga tttgcaggac agtttacgat agtgagtatg cagaatagtt aacacctttg 4440 ttttatcctt ttgtgtctta attatatgat ataaaggcgc ctggcgttat cggatagtaa 4500 tagatgctag ttatcaacat ttcacaattg aaggaaataa agttgaagta ctcaacaaaa 4560 acttacttca gaattaaatt tttgggggga acataggcat cctatgacag gtgaccacaa 4620 gcccctcaac gcaatctaat attttacaaa gtggtaaaat tctttcgttc ttcgttttaa 4680 tatacagtca tttattgatt ctattac 4707 <210> 90 <211> 4137 <212> DNA <213> Artificial Sequence <220> <223> Ost1-pro-alpha-f(l)-OXC53 <400> 90 caagaaggat tttctggcat ttgcttattg aaagcgtctt caattatatt aaaactaaaa 60 ttgaagtttc caaaaaagaa agatagaact gatattagca aattgtgtga caagaaagaa 120 cggatgacac agtggttaga aatttcaatt ttgatgaact gagaataata atattatgct 180 cccctggatt ttatgcgaag acactgctga aaaaatttct gatatatgca gagaaggagc 240 aaataagcca gttttaagga accgagataa gctgttttcg cccattgttc tagttctaca 300 aaatatctac agggaatcga tgaggttgta agaaatcctg aatactctat gatagtgcat 360 aacactaaaa agttgaaaga atcccgtatc atggacgatt tccttgaaca tttgagcaaa 420 gacgataaca aagcatggta tggcgcggaa gaaaccgaga gagctgcaaa attagatgca 480 atagaaacac tacttattac agatagtgta ctaaaaagga acgacgtgaa aaaacgtgaa 540 aaatacctag acctaataga gaatagtgga aacaacaatg gcaaaatatt cgtactcagt 600 acttcaaaaa tcacagtgag caacttgaca aaccaacacc ttgccaacag ggagttcttc 660 agagacatgg aggctcaaaa cgaaattatt gacagcctag acatcaatag tcatacaaca 720 gaaagcgacc acccaacttt ggctgataat agcgtataaa caatgcatac tttgtacgtt 780 caaaatacaa tgcagtagat atatttatgc atattacata taatacatat cacataggaa 840 gcaacaggcg cgttggactt ttaattttcg aggaccgcga atccttacat cacacccaat 900 cccccacaag tgatccccca cacaccatag cttcaaaatg tttctactcc ttttttactc 960 ttccagattt tctcggactc cgcgcatcgc cgtaccactt caaaacaccc aagcacagca 1020 tactaaattt cccctctttc ttcctctagg gtgtcgttaa ttacccgtac taaaggtttg 1080 gaaaagaaaa aagacaccgc ctcgtttctt tttcttcgtc gaaaaaggca ataaaaattt 1140 ttatcacgtt tctttttctt gaaaattttt ttttttgatt tttttctctt tcgatgacct 1200 cccattgata tttaagttaa taaacggtca tcaatttctc aagtttcagt ttcatttttc 1260 ttgttctatt acaacttttt ttacttcttg ctcattagaa agaaagcata gcaatctaat 1320 ctaagtttta attacaaaat gaggcaggtt tggttctctt ggattgtggg attgttccta 1380 tgttttttca acgtgtcttc tgctgcttca gtcaacacta caacagaaga tgaaacggca 1440 caaattccgg ctgaagctgt catcggttac tcagatttag aaggggattt cgatgttgct 1500 gttttgccat tttccaacag cacaaataac gggttattgt ttataaatac tactattgcc 1560 agcattgctg ctaaagaaga aggggtatct ctcgagaaaa gagaggctga agctatgcca 1620 agagaaaact tcttgaagtg tttctctaag catatcccaa acaacgttgc taacccaaag 1680 ttggtctata ctcaacacga tcaattgtat atgtctattt tgaactctac tattcaaaat 1740 ttgagattca tttctgatac caccccaaaa ccattggtca ttgtcactcc ttccaacaac 1800 tcccatatcc aagctactat tttgtgttct aagaaggtcg gtttgcaaat cagaaccaga 1860 tctggtggtc acgatgccga gggtatgtcc tacatttctc aagttccttt tgtcgttgtt 1920 gatttgagaa acatgcactc catcaaaatt gatgttcact cccaaaccgc ctgggtcgaa 1980 gctggtgcca ctttgggtga agtctactac tggattaatg aaaagaatga aaatttgtcc 2040 ttcccaggtg gttactgtcc aaccgttggt gttggtggtc acttctccgg tggtggttac 2100 ggtgctttga tgagaaacta cggtttagct gctgataaca ttatcgacgc ccacttggtt 2160 aatgttgatg gtaaagtctt ggacagaaaa tctatgggtg aagatttgtt ttgggccatt 2220 agaggtggtg gtggtgagaa cttcggtatc attgctgcct ggaagatcaa attggttgct 2280 gttccatcta agtccactat tttttccgtt aagaagaaca tggaaatcca tggtttagtt 2340 aaattattta acaagtggca aaacattgcc tacaagtacg ataaagattt ggttttgatg 2400 acccatttca ttactaagaa tattactgac aatcacggta agaacaagac taccgttcac 2460 ggttacttct cttctatttt ccacggtggt gtcgactcct tagttgattt gatgaacaaa 2520 tcctttccag agttgggtat taagaagact gattgtaagg aattctcttg gattgacacc 2580 accatcttct actctggtgt cgtcaacttt aacactgcca actttaagaa ggaaatttta 2640 ttggatagat ccgctggtaa gaagaccgct ttttccatca aattggatta cgtcaagaag 2700 ccaatccctg agactgccat ggtcaagatc ttggaaaagt tgtatgaaga agacgttggt 2760 gctggtatgt acgttttata tccatacggt ggtattatgg aagagatttc cgaatccgct 2820 attccattcc cacatagagc tggtatcatg tacgaattgt ggtacactgc ttcttgggaa 2880 aaacaagaag ataatgaaaa gcatattaac tgggttagat ccgtttacaa cttcaccact 2940 ccatatgttt ctcaaaaccc aagattggct tacttgaact atagagattt ggatttgggt 3000 aagactaacc acgcctctcc aaacaattac actcaagcta gaatctgggg tgaaaaatac 3060 ttcggtaaga acttcaacag attagtcaaa gtcaagacca aagttgaccc aaacaacttc 3120 ttcagaaacg agcaatccat tcctccattg cctccacacc atcacggcca tcatcaccat 3180 caccattagc tcgagcatgc atctagaggg ccgcatcatg taattagtta tgtcacgctt 3240 acattcacgc cctcccccca catccgctct aaccgaaaag gaaggagtta gacaacctga 3300 agtctaggtc cctatttatt tttttatagt tatgttagta ttaagaacgt tatttatatt 3360 tcaaattttt cttttttttc tgtacagacg cgtgtacgca tgtaacatta tactgaaaac 3420 cttgcttgag aaggttttgg gacgctcgaa ggctttaatt tgccaatagc ttgcagcgta 3480 gctaaactct aaaatttatc taaatcactc atataaaccg aacccttccc cttccgctta 3540 tagtacagta cctatacatt tcataaacat ggcatggcga tcagcgccaa acaatatgga 3600 aaatccacag aaagctattc attgaaaaaa tagtacaaat aagtcacatg atgatatttg 3660 attttattat atttttaaaa aaagtaaaaa ataaaaagta gtttattttt aaaaaataaa 3720 atttaaaata ttagtgtatt tgatttccga aagttaaaaa agaaatagta agaaatatat 3780 atttcattga atggatatat gaaacgttta ctggtggaag ttttgctcat atattattat 3840 tcaatagaag taataaagaa aaagttggta aagcaactta acagtaaaaa ggtaatgatt 3900 gaaaaagttt ttgaacatct aagctatatg ttgatgggtt tacaatttta ccattagtac 3960 tcatgcctat acttttctgt tcgtccttaa tgtccgcgat ttagagcaat cattgaaagt 4020 actagataca ttttagccag agaggactcg ttgacgtaga attaaaattc aaatgaattt 4080 ccgccccatt catatacccc aaataacaaa catattaaaa cttcataatt attcaaa 4137 <210> 91 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> Wild Type OAC Protein <400> 91 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Val Asn Leu Val Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Tyr Trp Gly Lys Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Thr Ile Gln Asp Tyr Ile Ile His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Val Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Arg Lys Gly 100 <210> 92 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> Variant OAC Protein - General <220> <221> MISC_FEATURE <222> (1)..(102) <223> Xaa is any amino acid <400> 92 Met Ala Val Lys His Leu Ile Val Leu Lys Phe Lys Asp Glu Ile Thr 1 5 10 15 Glu Ala Gln Lys Glu Glu Phe Phe Lys Thr Tyr Xaa Asn Leu Xaa Asn 20 25 30 Ile Ile Pro Ala Met Lys Asp Val Xaa Trp Xaa Xaa Asp Val Thr Gln 35 40 45 Lys Asn Lys Glu Glu Gly Tyr Thr His Ile Val Glu Val Thr Phe Glu 50 55 60 Ser Val Glu Xaa Ile Gln Asp Tyr Ile Xaa His Pro Ala His Val Gly 65 70 75 80 Phe Gly Asp Xaa Tyr Arg Ser Phe Trp Glu Lys Leu Leu Ile Phe Asp 85 90 95 Tyr Thr Pro Xaa Lys Xaa 100 <210> 93 <211> 232 <212> PRT <213> Artificial Sequence <220> <223> mScarlet Protein <400> 93 Met Val Ser Lys Gly Glu Ala Val Ile Lys Glu Phe Met Arg Phe Lys 1 5 10 15 Val His Met Glu Gly Ser Met Asn Gly His Glu Phe Glu Ile Glu Gly 20 25 30 Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys 35 40 45 Val Thr Lys Gly Gly Pro Leu Pro Phe Ser Trp Asp Ile Leu Ser Pro 50 55 60 Gln Phe Met Tyr Gly Ser Arg Ala Phe Thr Lys His Pro Ala Asp Ile 65 70 75 80 Pro Asp Tyr Tyr Lys Gln Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg 85 90 95 Val Met Asn Phe Glu Asp Gly Gly Ala Val Thr Val Thr Gln Asp Thr 100 105 110 Ser Leu Glu Asp Gly Thr Leu Ile Tyr Lys Val Lys Leu Arg Gly Thr 115 120 125 Asn Phe Pro Pro Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp 130 135 140 Glu Ala Ser Thr Glu Arg Leu Tyr Pro Glu Asp Gly Val Leu Lys Gly 145 150 155 160 Asp Ile Lys Met Ala Leu Arg Leu Lys Asp Gly Gly Arg Tyr Leu Ala 165 170 175 Asp Phe Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Met Pro Gly 180 185 190 Ala Tyr Asn Val Asp Arg Lys Leu Asp Ile Thr Ser His Asn Glu Asp 195 200 205 Tyr Thr Val Val Glu Gln Tyr Glu Arg Ser Glu Gly Arg His Ser Thr 210 215 220 Gly Gly Met Asp Glu Leu Tyr Lys 225 230

Claims (22)

  1. 올리베톨산(OVLa)을 생산하거나 식물성 칸나비노이드(phytocannabinoid)를 생산하는 능력을 포함하는 이종 숙주 세포에서 올리베톨산(OVLa) 또는 상기 올리베톨산으로부터 생산된 식물성 칸나비노이드를 생산하는 방법으로서, 상기 방법은,
    야생형 올리베톨산 시클라아제(olivetolic acid cyclase; OAC) 단백질에 대해 적어도 6개의 아미노산 돌연변이들을 갖는 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 뉴클레오티드로 상기 숙주 세포를 형질전환시키는 단계; 및
    상기 형질전환된 숙주 세포를 배양하여 올리베톨산 및/또는 상기 올리베톨산으로부터 유래된 식물성 칸나비노이드를 생산하는 단계;를 포함하고,
    이때 상기 변이체 올리베톨산 시클라아제(OAC) 단백질은 서열 번호: 91에 기재된 야생형 올리베톨산 시클라아제(OAC) 단백질 서열과 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 서열 동일성을 포함하는 것인, 방법.
  2. 제1항에 있어서, 상기 적어도 6개의 아미노산 돌연변이들 중 적어도 4개의 돌연변이들은 서열 번호: 91의 잔기 28, 31, 41, 43, 44, 68, 74, 84, 100, 및 102로 이루어진 그룹으로부터 선택된 잔기들에 있는 것인, 방법.
  3. 제2항에 있어서, 아미노산 잔기 28, 31, 41, 43, 44, 68, 74, 84, 100, 또는 102에 있는 상기 적어도 4개의 돌연변이들 중 적어도 하나의 돌연변이는 보존적 아미노산 치환인 것인, 방법.
  4. 제2항 또는 제3항에 있어서, 아미노산 잔기 28, 31, 41, 43, 44, 68, 74, 84, 100, 또는 102에 있는 상기 적어도 4개의 돌연변이들 중 적어도 하나의 돌연변이는 비보존적 아미노산 치환인 것인, 방법.
  5. 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 변이체 올리베톨산 시클라아제(OAC) 단백질은 28, 31, 41, 43, 44, 68, 74, 84, 100, 또는 102번 위치에 있는 적어도 10개, 적어도 9개, 적어도 8개, 적어도 7개, 적어도 6개, 또는 적어도 5개의 아미노산 잔기들에서 아미노산 치환을 갖는 것인, 방법.
  6. 제1항 내지 제5항 중 어느 한 항에 있어서, 잔기 28, 31, 41, 43, 44, 68, 74, 84, 100, 또는 102 이외의 잔기에서의 모든 아미노산 돌연변이는 보존적 아미노산 치환인 것인, 방법.
  7. 제1항 내지 제6항 중 어느 한 항에 있어서, 상기 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 뉴클레오티드는 다음을 포함하는 서열을 갖는 것인, 방법:
    (a) 서열 번호: 5, 서열 번호: 3, 서열 번호: 4, 또는 서열 번호: 6 내지 서열 번호: 39에 기재된 뉴클레오티드 서열;
    (b) (a)의 서열과 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99% 동일성을 갖는 뉴클레오티드 서열; 또는
    (c) (a)의 서열을 갖는 뉴클레오티드의 상보적 가닥과 하이브리드화되는 뉴클레오티드 서열.
  8. 제1항 내지 제6항 중 어느 한 항에 있어서, 상기 변이체 올리베톨산 시클라아제(OAC) 단백질은 서열 번호: 42, 서열 번호: 40, 서열 번호: 41, 및 서열 번호: 43 내지 서열 번호: 76으로 이루어진 그룹으로부터 선택된 서열, 및 상기 서열과 적어도 90%, 적어도 95%, 또는 적어도 99%의 서열 동일성을 갖는 서열을 포함하는 것인, 방법.
  9. 제1항 내지 제6항 중 어느 한 항에 있어서, 상기 야생형 올리베톨산 시클라아제 단백질(OAC)에 대한 적어도 6개의 아미노산 돌연변이들 중 적어도 4개의 돌연변이들은 하기로 이루어진 그룹으로부터 선택되는 것인, 방법:
    V28A;
    V31G;
    Y41T, Y41S, 또는 Y41V;
    K44V;
    T68L 또는 T68R;
    I74E, I74R, I74D, 또는 I74G;
    V84R;
    R100M 또는 R100E; 및
    G102R, G102S, 또는 G102STOP.
  10. 제1항 내지 제9항 중 어느 한 항에 있어서, 상기 숙주 세포는 올리베톨산 시클라아제(OAC) 야생형(서열 번호: 91)으로부터 표시된 치환들이 존재하는 다음 서열들 중 어느 하나의 서열과 적어도 85%, 적어도 90%, 적어도 95%, 적어도 99%, 또는 100% 서열 동일성을 갖는 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 뉴클레오티드로 형질전환되는 것인, 방법:
    V28A/V31G/Y41S/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102R (서열 번호:42),
    V28A/Y41T/G43SILENT(=GGG)/T68L/I74E/V84R/R100M/G102R (서열 번호:40),
    Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R (서열 번호:41),
    V28A/Y41T/G43SILENT(=GGG)/T68L/I74G/V84R/R100E (서열 번호:43),
    V28A/Y41T/G43SILENT(=GGG)/K44V/T68L/I74D/V84R/R100M/G102R (서열 번호:44),
    V28A/Y41T/G43SILENT(=GGG)/T68L/I74D/V84R/G102R (서열 번호:45),
    V28A/Y41T/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102R (서열 번호:46),
    Y41T/G43SILENT(=GGG)/T68R/I74R/V84R/R100M/G102STOP (서열 번호:47),
    V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/R100E/G102R (서열 번호:48),
    V28A/Y41T/G43SILENT(=GGG)/K44V/T68R/I74G/V84R/G102STOP (서열 번호:49),
    V28A/Y41T/G43SILENT(=GGG)/K44V/T68R/I74G/V84R/G102STOP (서열 번호:50),
    V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74E/V84R/R100E (서열 번호:51),
    V28A/Y41S/G43SILENT(=GGG)/T68R/I74R/V84R/R100M/G102STOP (서열 번호:52),
    Y41T/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/G102R (서열 번호:53),
    V28A/Y41T/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100E/G102R (서열 번호:54),
    V28A/V31G/Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R (서열 번호:55),
    V28A/G43SILENT(=GGG)/K44V/I74D/V84R/R100E/G102R(=CGC) (서열 번호:56),
    V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/G102R (서열 번호:57),
    Y41T/G43SILENT(=GGG)/T68L/I74G/V84R/R100M/G102R (서열 번호:58),
    V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100E/G102R (서열 번호:59),
    V31G/Y41S/G43SILENT(=GGG)/K44V/T68R/V84R/R100E (서열 번호:60),
    V28A/Y41V/G43SILENT(=GGG)/T68L/I74D/R100E/G102STOP (서열 번호:61)
    V28A/Y41V/G43SILENT(=GGG)/T68R/I74G/V84R/R100M/G102R (서열 번호:62),
    V31G/G43SILENT(=GGG)/I74G/V84R/R100E (서열 번호:63),
    V28A/Y41S/G43SILENT(=GGG)/K44V/T68R/I74R/V84R/R100M/G102R (서열 번호:64),
    V28A/V31G/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R (서열 번호:65),
    V28A/Y41V/G43SILENT(=GGG)/K44V/T68L/I74G/V84R/R100M/G102R (서열 번호:66),
    V28A/V31G/G43SILENT(=GGG)/T68L/I74R/V84R/R100E/G102R (서열 번호:67),
    V31G/Y41V/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/R100E/G102STOP (서열 번호:68),
    V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74D/V84R/G102R (서열 번호:69),
    V31G/Y41T/G43SILENT(=GGG)/K44V/T68R/I74D/V84R/R100E/G102R (서열 번호:70),
    V28A/Y41S/G43SILENT(=GGG)/K44V/T68R/I74G/V84R/R100M/G102R (서열 번호:71),
    V28A/Y41V/G43SILENT(=GGG)/K44V/I74R/R100E/G102STOP (서열 번호:72),
    V28A/V31G/Y41T/G43SILENT(=GGG)/K44V/I74E/V84R/R100M/G102R (서열 번호:73),
    V28A/G43SILENT(=GGG)/K44V/T68R/I74E/V84R/R100E/G102STOP (서열 번호:74),
    V31G/Y41T/G43SILENT(=GGG)/K44V/T68L/I74D/V84R/G102R (서열 번호:75), 또는
    Y41V/G43SILENT(=GGG)/K44V/T68L/I74R/V84R/G102R (서열 번호:76).
  11. 제1항 내지 제10항 중 어느 한 항에 있어서, 상기 식물성 칸나비노이드는 칸나비게롤(cannabigerol; CBG), 칸나비게롤산(cannabigerolic acid; CBGa), 칸나비게로바린(cannabigerovarin; CBGV), 칸나비게로바린산(cannabigerovarinic acid; CBGVa), 칸나비게로신(cannabigerocin; CBGO), 칸나비게로신산(cannabigerocinic acid; CBGOa), 칸나비바린(cannabivarin), 테트라하이드로칸나비놀(tetrahydrocannabinol; THC), 또는 테트라하이드로칸나비놀산(tetrahydrocannabinolic acid; THCa)인 것인, 방법.
  12. 제1항 내지 제11항 중 어느 한 항에 있어서, 상기 숙주 세포는 디바린산 신타아제(divarinic acid synthase)를 추가로 포함하여 디바린산을 생산하는 것인, 방법.
  13. 제1항 내지 제12항 중 어느 한 항에 있어서, 상기 숙주 세포는 효모 세포, 박테리아 세포, 진균 세포, 원생생물 세포, 또는 식물 세포인 것인, 방법.
  14. 제13항에 있어서, 상기 숙주 세포는 사카로마이세스 세레비시아에(S. cerevisiae), 에스케리키아 콜라이(E. coli), 야로위아 리폴리티카(Yarrowia lipolytica), 또는 코마가타엘라 파피(Komagataella phaffii)인 것인, 방법.
  15. 제1항 내지 제14항 중 어느 한 항에 있어서, 상기 형질전환된 숙주 세포는 폴리케티드 신타아제(polyketide synthase) 효소를 암호화하는 폴리뉴클레오티드 및/또는 프레닐트랜스퍼라아제(prenyltransferase) 효소를 암호화하는 폴리뉴클레오티드를 추가로 포함하는 것인, 방법.
  16. 서열 번호: 92와 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99% 서열 동일성을 갖는 아미노산 서열을 포함하는 올리베톨산 시클라아제 활성을 갖는 단리된 폴리펩티드로서, 이때 서열 번호: 92는 서열 번호: 91에 대해 6개 이상의 아미노산 잔기들의 돌연변이들을 포함하며, 상기 돌연변이들은 서열 번호: 91의 잔기 28, 31, 41, 43, 44, 68, 74, 84, 100, 및 102로 이루어진 그룹으로부터 선택된 위치들에 위치하는 것인, 단리된 폴리펩티드.
  17. 제16항에 있어서, 상기 단리된 폴리펩티드는 서열 번호: 42, 서열 번호: 40, 서열 번호: 41, 또는 서열 번호: 43 내지 서열 번호: 76에 기재된 아미노산 서열을 포함하는, 단리된 폴리펩티드.
  18. 다음을 포함하는 단리된 폴리뉴클레오티드:
    (a) 서열 번호: 5, 서열 번호: 3, 서열 번호: 4, 또는 서열 번호: 6 내지 서열 번호: 39에 기재된 뉴클레오티드 서열;
    (b) (a)의 뉴클레오티드 서열과 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 동일성을 갖는 뉴클레오티드 서열; 또는
    (c) (a)의 서열을 갖는 뉴클레오티드의 상보적 가닥과 하이브리드화되는 뉴클레오티드 서열.
  19. 야생형 올리베톨산 시클라아제(OAC) 단백질에 대해 6개 이상의 아미노산 돌연변이들을 갖는 서열 번호: 92에 기재된 서열을 포함하는 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 제18항에 기재된 폴리뉴클레오티드를 포함하는 발현 벡터.
  20. 제19항에 있어서, 상기 변이체 올리베톨산 시클라아제(OAC) 단백질을 암호화하는 폴리뉴클레오티드는 서열 번호: 5, 서열 번호: 3, 서열 번호: 4, 또는 서열 번호: 6 내지 서열 번호: 39에 기재된 뉴클레오티드 서열을 포함하는 것인, 발현 벡터.
  21. 제19항 또는 제20항에 기재된 발현 벡터로 형질전환된 숙주 세포.
  22. 제21항에 있어서, 상기 숙주 세포는 폴리케티드 신타아제 효소를 암호화하는 폴리뉴클레오티드 및/또는 프레닐트랜스퍼라아제 효소를 암호화하는 폴리뉴클레오티드를 추가로 포함하는, 숙주 세포.
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