AU2019397401A1 - Engineered tyrosine ammonia lyase - Google Patents
Engineered tyrosine ammonia lyase Download PDFInfo
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- AU2019397401A1 AU2019397401A1 AU2019397401A AU2019397401A AU2019397401A1 AU 2019397401 A1 AU2019397401 A1 AU 2019397401A1 AU 2019397401 A AU2019397401 A AU 2019397401A AU 2019397401 A AU2019397401 A AU 2019397401A AU 2019397401 A1 AU2019397401 A1 AU 2019397401A1
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- Prior art keywords
- ammonia lyase
- tyrosine ammonia
- seq
- recombinant
- positions
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
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- C12P13/225—Tyrosine; 3,4-Dihydroxyphenylalanine
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- C—CHEMISTRY; METALLURGY
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- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
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Landscapes
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| PCT/US2019/064891 WO2020123286A1 (en) | 2018-12-14 | 2019-12-06 | Engineered tyrosine ammonia lyase |
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Family Cites Families (77)
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| US6309883B1 (en) | 1994-02-17 | 2001-10-30 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
| US6395547B1 (en) | 1994-02-17 | 2002-05-28 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| US6995017B1 (en) | 1994-02-17 | 2006-02-07 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
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| US6406855B1 (en) | 1994-02-17 | 2002-06-18 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
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| US6117679A (en) | 1994-02-17 | 2000-09-12 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| US6335160B1 (en) | 1995-02-17 | 2002-01-01 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
| US6165793A (en) | 1996-03-25 | 2000-12-26 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| US5837458A (en) | 1994-02-17 | 1998-11-17 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
| US20060257890A1 (en) | 1996-05-20 | 2006-11-16 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
| US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
| FI964808A0 (fi) | 1994-06-03 | 1996-12-02 | Novo Nordisk Biotech Inc | Puhdistetut Myceliophthora lakkaasit ja niitä koodaavat nukleiinihapot |
| CN101659926A (zh) | 1994-06-30 | 2010-03-03 | 诺沃奇梅兹有限公司 | 非毒性、非产毒性、非致病性镰孢属表达系统及所用启动子和终止子 |
| FI104465B (fi) | 1995-06-14 | 2000-02-15 | Valio Oy | Proteiinihydrolysaatteja allergioiden hoitamiseksi tai estämiseksi, niiden valmistus ja käyttö |
| US6096548A (en) | 1996-03-25 | 2000-08-01 | Maxygen, Inc. | Method for directing evolution of a virus |
| US6506602B1 (en) | 1996-03-25 | 2003-01-14 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| US7148054B2 (en) | 1997-01-17 | 2006-12-12 | Maxygen, Inc. | Evolution of whole cells and organisms by recursive sequence recombination |
| WO1998031816A1 (en) | 1997-01-17 | 1998-07-23 | Regents Of The University Of Minnesota | Dna molecules and protein displaying improved triazine compound degrading ability |
| US6326204B1 (en) | 1997-01-17 | 2001-12-04 | Maxygen, Inc. | Evolution of whole cells and organisms by recursive sequence recombination |
| KR100570935B1 (ko) | 1997-01-17 | 2006-04-13 | 맥시겐, 인크. | 반복적 서열 재조합에 의한 전세포 및 유기체의 개량 방법 |
| US6537746B2 (en) | 1997-12-08 | 2003-03-25 | Maxygen, Inc. | Method for creating polynucleotide and polypeptide sequences |
| US6484105B2 (en) | 1998-04-02 | 2002-11-19 | Maxyag, Inc. | Method for obtaining a plant with a genetic lesion in a gene sequence |
| IL139093A0 (en) | 1998-05-01 | 2001-11-25 | Maxygen Inc | Optimization of pest resistance genes using dna shuffling |
| IL140125A0 (en) | 1998-06-17 | 2002-02-10 | Maxygen Inc | Method for producing polynucleotides with desired properties |
| US6365408B1 (en) | 1998-06-19 | 2002-04-02 | Maxygen, Inc. | Methods of evolving a polynucleotides by mutagenesis and recombination |
| JP2002522072A (ja) | 1998-08-12 | 2002-07-23 | マキシジェン, インコーポレイテッド | 工業用化学薬品の製造のためのモノオキシゲナーゼ遺伝子のdnaシャッフリング。 |
| JP2002526107A (ja) | 1998-10-07 | 2002-08-20 | マキシジェン, インコーポレイテッド | マイコトキシンの解毒のための核酸を生成するためのdnaシャッフリング |
| WO2000028018A1 (en) | 1998-11-10 | 2000-05-18 | Maxygen, Inc. | Modified adp-glucose pyrophosphorylase for improvement and optimization of plant phenotypes |
| JP4221100B2 (ja) | 1999-01-13 | 2009-02-12 | エルピーダメモリ株式会社 | 半導体装置 |
| US6917882B2 (en) | 1999-01-19 | 2005-07-12 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
| US6376246B1 (en) | 1999-02-05 | 2002-04-23 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US6436675B1 (en) | 1999-09-28 | 2002-08-20 | Maxygen, Inc. | Use of codon-varied oligonucleotide synthesis for synthetic shuffling |
| US6368861B1 (en) | 1999-01-19 | 2002-04-09 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US7702464B1 (en) | 2001-08-21 | 2010-04-20 | Maxygen, Inc. | Method and apparatus for codon determining |
| ES2341217T3 (es) | 1999-01-19 | 2010-06-17 | Maxygen, Inc. | Recombinacion de acidos nucleicos mediada por oligonucleotidos. |
| US7873477B1 (en) | 2001-08-21 | 2011-01-18 | Codexis Mayflower Holdings, Llc | Method and system using systematically varied data libraries |
| US20070065838A1 (en) | 1999-01-19 | 2007-03-22 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US7024312B1 (en) | 1999-01-19 | 2006-04-04 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
| US8457903B1 (en) | 1999-01-19 | 2013-06-04 | Codexis Mayflower Holdings, Llc | Method and/or apparatus for determining codons |
| US6961664B2 (en) | 1999-01-19 | 2005-11-01 | Maxygen | Methods of populating data structures for use in evolutionary simulations |
| JP2003524394A (ja) | 1999-02-11 | 2003-08-19 | マキシジェン, インコーポレイテッド | ハイスループット質量分析法 |
| AU3391900A (en) | 1999-03-05 | 2000-09-21 | Maxygen, Inc. | Encryption of traits using split gene sequences |
| US6703240B1 (en) | 1999-04-13 | 2004-03-09 | Maxygar, Inc. | Modified starch metabolism enzymes and encoding genes for improvement and optimization of plant phenotypes |
| US7430477B2 (en) | 1999-10-12 | 2008-09-30 | Maxygen, Inc. | Methods of populating data structures for use in evolutionary simulations |
| US6519065B1 (en) | 1999-11-05 | 2003-02-11 | Jds Fitel Inc. | Chromatic dispersion compensation device |
| US6686515B1 (en) | 1999-11-23 | 2004-02-03 | Maxygen, Inc. | Homologous recombination in plants |
| IL150291A0 (en) | 2000-01-11 | 2002-12-01 | Maxygen Inc | Integrated systems and methods for diversity generation and screening |
| EP1272967A2 (en) | 2000-03-30 | 2003-01-08 | Maxygen, Inc. | In silico cross-over site selection |
| JP2004508011A (ja) | 2000-04-03 | 2004-03-18 | マキシジェン, インコーポレイテッド | スブチリシン変異体 |
| US7747391B2 (en) | 2002-03-01 | 2010-06-29 | Maxygen, Inc. | Methods, systems, and software for identifying functional biomolecules |
| US20050084907A1 (en) | 2002-03-01 | 2005-04-21 | Maxygen, Inc. | Methods, systems, and software for identifying functional biomolecules |
| JP5319865B2 (ja) | 2002-03-01 | 2013-10-16 | コデクシス メイフラワー ホールディングス, エルエルシー | 機能的生体分子を同定する方法、システム、およびソフトウェア |
| EP1488335A4 (en) | 2002-03-09 | 2006-11-15 | Maxygen Inc | OPTIMIZING CROSSOVER POINTS FOR THE ADJUSTED EVOLUTION |
| JP2007502124A (ja) | 2003-08-11 | 2007-02-08 | コデクシス, インコーポレイテッド | 改良ケトレダクターゼポリペプチドおよび関連ポリヌクレオチド |
| WO2006034373A2 (en) | 2004-09-17 | 2006-03-30 | Biomarin Pharmaceutical Inc. | Variants and chemically-modified variants of phenylalanine ammonia-lyase |
| EP2886658A1 (en) | 2005-03-10 | 2015-06-24 | BASF Enzymes LLC | Lyase enzymes, nucleic acids encoding them and methods for making and using them |
| US7531341B1 (en) * | 2006-06-12 | 2009-05-12 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof |
| US7534595B2 (en) | 2006-06-12 | 2009-05-19 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof |
| US20090011400A1 (en) | 2006-12-01 | 2009-01-08 | The Salk Institute for Biological Studies and The Regents of the University of California | Substrate switched ammonia lyases and mutases |
| US7560263B2 (en) | 2007-08-17 | 2009-07-14 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of treating cancer using compositions thereof |
| US8504498B2 (en) | 2008-02-12 | 2013-08-06 | Codexis, Inc. | Method of generating an optimized, diverse population of variants |
| EP2250594B1 (en) | 2008-02-12 | 2017-04-19 | Codexis, Inc. | Method of generating an optimized, diverse population of variants |
| US20090312196A1 (en) | 2008-06-13 | 2009-12-17 | Codexis, Inc. | Method of synthesizing polynucleotide variants |
| US8383346B2 (en) | 2008-06-13 | 2013-02-26 | Codexis, Inc. | Combined automated parallel synthesis of polynucleotide variants |
| DK3023494T3 (en) | 2008-06-13 | 2019-02-25 | Codexis Inc | PROCEDURE FOR SYNTHESIS OF POLYNUCLEOTIDE VARIETIES |
| ES2690542T3 (es) | 2010-02-04 | 2018-11-21 | Biomarin Pharmaceutical Inc. | Método para purificar variantes de fenilalanina amoníaco-liasa procariotas |
| DK2726651T3 (en) | 2011-06-28 | 2019-01-28 | Codexis Inc | PROTEIN INVARIANT GENERATION BY REGION SHUFFLING |
| EP2825647A4 (en) | 2012-03-15 | 2015-10-14 | Codexis Inc | METHODS OF GENE REARRANGING |
| US20150133698A1 (en) | 2012-04-20 | 2015-05-14 | Codexis, Inc. | Production of fatty alcohols from engineered microorganisms |
| US9665694B2 (en) | 2013-01-31 | 2017-05-30 | Codexis, Inc. | Methods, systems, and software for identifying bio-molecules with interacting components |
| NZ713396A (en) | 2013-04-18 | 2020-06-26 | Codexis Inc | Engineered phenylalanine ammonia lyase polypeptides |
| BR112016006284B1 (pt) | 2013-09-27 | 2022-07-26 | Codexis, Inc | Método implementado por computador, produto de programa de computador, e, sistema de computador |
| RU2016116253A (ru) | 2013-09-27 | 2017-11-01 | Кодексис, Инк. | Автоматизированный скрининг вариантов фермента |
| WO2015161019A1 (en) * | 2014-04-16 | 2015-10-22 | Codexis, Inc. | Engineered tyrosine ammonia lyase |
| CA3122524A1 (en) * | 2018-12-14 | 2020-06-18 | Codexis, Inc. | Engineered tyrosine ammonia lyase |
-
2019
- 2019-12-06 CA CA3122524A patent/CA3122524A1/en active Pending
- 2019-12-06 US US16/705,656 patent/US11473077B2/en active Active
- 2019-12-06 EP EP19897046.9A patent/EP3893860A4/en not_active Withdrawn
- 2019-12-06 JP JP2021533201A patent/JP2022513199A/ja active Pending
- 2019-12-06 SG SG11202105668PA patent/SG11202105668PA/en unknown
- 2019-12-06 WO PCT/US2019/064891 patent/WO2020123286A1/en not_active Ceased
- 2019-12-06 AU AU2019397401A patent/AU2019397401A1/en not_active Abandoned
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2021
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2022
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- 2022-09-13 US US17/931,687 patent/US20230020928A1/en not_active Abandoned
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| JP2022513199A (ja) | 2022-02-07 |
| IL283894A (en) | 2021-07-29 |
| US11473077B2 (en) | 2022-10-18 |
| SG11202105668PA (en) | 2021-06-29 |
| US20230020928A1 (en) | 2023-01-19 |
| US20200190499A1 (en) | 2020-06-18 |
| EP3893860A1 (en) | 2021-10-20 |
| EP3893860A4 (en) | 2023-03-29 |
| WO2020123286A1 (en) | 2020-06-18 |
| US20230002752A1 (en) | 2023-01-05 |
| CA3122524A1 (en) | 2020-06-18 |
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