JPS58220694A - Improvement of productivity of antibiotic - Google Patents

Abstract

PURPOSE:In preparing antibiotics by cultivating microorganisms, to improve the productivity of antibiotics, by carrying out the cultivation under irradiation of light rays containing no ultraviolet light with <=a specific wave length. CONSTITUTION:Microorganisms are cultivated to give antibiotics, for example, a bacterium belonging to the genus Streptomyces is cultivated to give kanamycin, a fungi belonging to the genus Penicillium to give penicilling, and a fungus belonging to the genus Cephalosporium to give cephalosporinc. When the cultivation of these microorganisms is carried out under irradiation of light rays containing no ultraviolet light with <=340nm wave length, the production of these antibiotics is increased. Since the cultivation is carried out in a dark tank made of stainless steel, etc., artificial light rays are used, and a light filter is used to give the light rays having the above-mentioned condition.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for culturing antibiotic-producing microorganisms, and more specifically, the present invention relates to a method for culturing antibiotic-producing microorganisms, and more specifically, culturing antibiotic-producing microorganisms under irradiation with light in a specific wavelength range to increase the productivity of the antibiotic. on how to improve.

In the process of researching how light conditions affect the growth of various useful plants, controlling the proliferation of disease-causing fungi on useful plants, cultivating algal plants, etc. In addition, the present inventors have discovered that the productivity of antibiotics is greatly improved when antibiotic-producing microorganisms are cultured under active irradiation with specific light that does not contain ultraviolet rays of 34 Q nm or less, leading to the completion of the present invention.

Thus, in accordance with the present invention, a method for culturing antibiotic-producing microorganisms and recovering antibiotics from the culture comprises irradiating the culture with light substantially free of ultraviolet radiation having a wavelength of at least 34 Q nrn or less. A method for improving antibiotic productivity is provided.

In this specification, [antibiotic-producing microorganisms] refers to antibiotics, i.e., acid-fast bacterium active substances, penicillins, cephalosporins, macrolides, aminoglycosides, tetracyclines, chloramphenicols, polysaccharides, etc. Peptide type, antifungal active substance, anticancer substance 1. It refers to microorganisms that have the ability to produce antifungal substances, enzymes, etc. within their cells or as metabolic products, and such microorganisms include molds, actinomycetes, bacteria, and yeasts.

Generally speaking, the method of the present invention can be applied to any type of microorganism, as is clear from the experience of the present inventors and the results of the examples described below. Although it can be expected to improve the productivity of antibiotics to some extent, the effect is particularly remarkable against microorganisms such as molds and actinomycetes.

Examples of typical microorganisms to which the method of the present invention can be applied are as follows. In addition, in the examples of microorganisms below, the name of the microorganism is shown in Japanese by the genus (Qgnus) and species (Species), and then the original hair (T) is shown.
"THEAMERICAN TYP"
E CULTURE C0LLECTIONJ (ATC
C) or I'lN5TITUTE FORFERME-
The storage number of NTATION 08AKA J (IFO) is shown in 0, and the name of the antibiotic or enzyme produced next is shown in <>.

[1] Molds (4) Penicillium (penicillium) Penicillium chrysogenum (p, chrysogenu)
m ) (ATCC, 12690iIFO9252) <p
enicillin') Penicillium ur-) - force x (p, urticae)
(ATCC10120)<6-Methylsalic
licacid, patrtlin〉 (B) Cephalosvolium maple (C: ephalo
sporium) Cephalosvolium acremonium ((::, acremonium) (ATCC115
50, IFO30053) <Cephaiospor
in C) (C) 7 sidium% (Fusidium
) Fucidium coccinenium (F”, coc
c ineum) (ATCC14700><Fusid
icacid〉0〕) Bacillomyces genus (pac c
i l omyces) Bacillomyces varioti (P, υarioti) (ATCC1114) <Va
riotin〉(υ Gurpurariahen (Cur vul
ar ia) Curvularia lunata (C, 1rbna)
t a ) (ATCC12017)<BreJ'eld
in> (D Claviceps genus (C1aviceps) Clavice, Bus pur brella (C, pur pur eα
) (A'l'CC14934)<Ergotalkal
oids ) (G) phycomyces (phy c
phycomyces plakesleeanus (ATCC620
0) (Caro tene) Among the above molds, 1. Molds belonging to the genus Penicillium and Cephalosporium are preferred.

[11] Actinomycetes Strephtomyces sp.
y c e s) Strephtomyces clavuligerus (S, clavuligerus) (ATCC2706
4)〈Cephamycin C) Strephtomyces lividus (S, l 1vidu
s ) (ATCC21178) <Lividomyci
n”) Strephtomyces-griseus (s, Qri8
eu8) (ATCC12475, 15395, 233
451IF0 13304><Indolmycin,
Cepha-mycin, CandicidinS
Streptomycin.

Cyclohexirn,ite,Chromomyc
inAs > Streftmyces fladeae (S, f
rad iae) (ATCC10745, 3355,
21096)〈pJeomycin, Tyl osi
n, phosphonomycin”:)1・11 Strephtomyces° Kanamycechus (S, ka
namyceticu8) (ATCC12853, IF
o 13414><Kanatnycin A, Kan
amycinB〉Streptomyces limosus (S
, rimosus) (ATCC 10970, 13324
) <Parorn, omycin, Oxytetracy
ctine〉Streftomyces tenebrarius (S, tenebrarius) (ATCC17920
) (Tobramycin') Strephtomyces ribosidaephicus (S, rib
osidificus) (ATCC21294) (Jt
i b o s t amycin) Strephtomyces aureofaciens (S, aureofaciens)
(ATCC10762)〈Chlortet
racycline, Ayfactin.

('fetracycline, ()xytetrac
ycline)〉Streftomyces-erythreus'<S, erythreu, 5) (ATCC11635
) <J, rythrom4) cin> Streftmyces halstedi (s, halste
dii) (ATCC10897)<Carbomyci
n〉Streftomyces ambohuesines (S, am
bo'faciens) (ATCC15154) <5p
ira mycin〉 Strephtomyces kitasatoensis (S, kita
satoensis) 4. eucomycirt〉Streptomyces antibiotics (S, antib
ioticus) (ATCC11891) (Olean
domy c in, ant inomy c
? ,? L> Streftmyces microfaciens (S, mycarofaciens) (ATCC2
1454) <Myde camy c in ) Strephtomyces hygroscopicus (S, hygro
Scopicus ) (ATCC10976) (Jda
ri dotnycin, Aza l omycin
.

HygromycinB) Strephtomyces-puniceus<S, punicer
bs) (ATCC, 19801) <Vj omy c
in') Strephtomyces cabreolus (S,
capreolus) (ATCC, 23892) <Ca
preomycin) Strephtomyces griseoverticilast (S, griseoverticilat)
us)〈Tuberactino-mycin) Strephtomyces olivaceus et al. (S, orch
i-dac'eus and others)<C
ycloserin〉Streftomyces niveus
S, n1veusand other (ATCC
, 19793) <Novobiocin) Strephtomyces mitakaensis (S, mi taka ensis) (ATCC
S, narb
onensis var ) (ATC:C.

17835 ) (Josamycin) Strephtomyces clavulibreus (S, clavulige
rus ) (ATCC, 27064) <C1avsLl
an, ic acid :) Strephtomyces olivaceus et al.
other) (ATCC, 3335) < Thiena
mycin) Strephtomyces venezuelae (S, venezuelae) (ATCC, 10595
) (Chloramphenicol) Strephtomyces tenebrarius (S, tenebrarius) (ATCC, 179
20)〈Apramycin,, Nebramycin
n) Strephtomyces hofensis (S, hofu
-en8i8> (ATCC, 21970) (Setdo
myc'in factor 5) Strephtomyces nodossus (S, nodosrbs) (ATCC
-14899)<kmphotericin B) Strephtomyces lincornensis (S, 1incol
nensis) (AI'CC, 25466) <Link
omycin) Strephtomyces sapporonensis (S, 5ap
po-ronensis) (ATCC, 21532)
<Bicyclomycin) Strephtomyces uoursei (S, uours
e i ) <Nystatin”) Strephtomyces hacjoensis (S, hac
hijoensis)〈Tr ichomic in
:) Streftmyces sp. (S', sp)
<Amphotericin 13. fillithr
amycin”) Strephtomyces erythrochromogenes (S, erythrochromogenes)
s ) < SarkOmycin :) Strephtomyces searchroi (S, 5ahachiroi) (-Carzi
Strephtomyces caesbitus (S, caespi-tO8u8)
(ATCC, 27422) <JAitomycinC>
Strephtomyces persetius (S, pe'rb
cetius) (ATCC, 29050, 27952)
<Dartnomycin, Adrian, yci
n') Strephtomyces verticillus (S, υ
ertici-11u8) (ATCC, 15003)
Bleomycin〉Streftomyces carzinostaticus (S, carzinostaticus)
) (ATCC, 15944) (Neocarzin
astatin〉Streftomyces galilaeus (
S. galila-eu8) (ATCC, 31133)
<Aclacinomycin”) Strephtomyces goldi-nensis (S-goldi-nensis) <
Arbrodox) Strephtomyces skewer virido-flavus (S, virido-flavus) <ATCC=
12631)〈Candihexin 5Cand
iditt) Streftmyces jamaicensis (S, jamaicensis) (No vo b
ioc in.

Strephtomyces orientalis (S, ori-e
ntalis) (ATCC, 21425) <Va
Strephtomyces albo-nigre (S, albo-ni(ler) (ATCC-124
61) <Pu'romycin) Streftmyces
Kasugaensis (S, kasuga-en8i8)
(ATCC, 15714) <Kasugamycin
) Strephtomyces verticillanthos (S, ve
rticillatts) (ATCC, 13495) (
Jlitomycin) Strephtomyces sioyaensis (S, 5ioyaensis) (ATCC-1398
9)<Siomycin): Strephtomyces lavendulae (S, 1avendulae) (ATCC-8664)
<5treptothricin) Streft Knowsei (S, noursei) (ATC
C011455) <Fungicidin) Streft. Birginiae (s, virginiae) (ATCC,
12630><St(17)hylomycin>Streft Alps (S, α1bus) (ATCC, 61
8) <Indolmycin) (B) Nocardia sp. (N, 8p) <Ansami toc'in
) Tukartia mediterranei (N, medi-t
erranei) (ATCC, 21271) <Ri
fCLmllCin > Tukartia Uniformis (N, uni for -mi8) CATL:C
021806) <Nocardicin”;> (0 Mira 0 Monospora h (Micromonospora)
Micromonospora brapulera et al. (kh, pur p
ur eaCLnd 0ther) (ATCC-1
5835><Gentamicin>Micromonospora inyoensis ovi, 1nyoensis> (ATcc, 276
00) (Sisomicin) Micromonospora oliba Esterospora (M, oli
voasterospora) (ATCC).

31010) <Fortinmicin) Micromonospora zagamiensis (M, sagar, 1ensis) (A, TCC-2
1826) (Sa gami c in ) CD) Gloactinomysis 飄(proactin)
omyces) Gloactinomysis frausitiphieri (p, fruct 1feri)
omycirV) (Q Actinoplanes (ACli)
nomyces) Actinoplanes levolis (A, 1
evoris)〈Levorin〉 saw) Actinoplanes genus (Actinoplanes)
s) Actinoplanes ligalaie (A, ligu
Among the above-mentioned actinomycetes, those belonging to the genus Streptomyces, Nocardia, and Micromonospora are preferred, and actinomycetes belonging to the genus Streptomyces are particularly preferred.

Cl) Bacteria (A) Bacillus spp. Bacillus circulans (ATC
C, 21557) <Butirosin> Bacillus phlevis (B, bγevis) (ATCC, 9999) <
Gra, m1cidinS> Pan/lz subtilis (B, 5ubt, 1lis) (ATCC314593)
<Bacitracin') Bacillus licheniformis (B, lichenifor-mz8) (AT
CC, 10716) <B (Icitracin) Bacillus autopolymyx
a ) (A'l'CC, 10401) < Polymyx
in) Bacillus colistinus (B, Colis
t 1nus)〈Co11stin〉 (13) :I Linebacterium b=,,X,ItA(
Corynebacterium) Corynebacterium sp. and other (C, sp, and other) <C: orynec
in”) (Q pseudomonas
as) Fusiudomonas sorbici = (pj+, 5orb
icinii)<5orbistins)
nia) (ATCC11595B) <, Pyrrolln
itrin〉Fushiudomonas aurelofinense (P, aureo7'c+, cigning) (ATCC1
13985)<phenazine-carbozyl
ic acid”;＞Fushiudomonas aeruginosa (
P, aerrbgi-n08(L) (ATCo, 19
429><Pyocyanine)
'1 Actinomadeura cα I/'Short story (A, cαrm
inata) (, Carminomyci
n)0) Cellulati, a79. (Serratia)
Cellulatia marcescens (S, rc e s c
ens ) (ATCC125179) <Prodig
iosin) ") Chromobacterium suma 4 (Chro
mobacterium) Chromobacterium violaceum (C, violaceum) (ATCC4553) <V
iolacein> Among the above-mentioned bacteria, bacteria belonging to the genus Bacillus and the genus Fuciudomonas are preferred.

Yeasts (A) Ascomycete yeast a) Schizosac caromyce, z, Schizosac
charo-myces) Charomyces bonhe (S, pombe)
(A'I'CC, 2476) <Alcoholic fermentation> b)
Saccharomyce pA (Saccharomyce o-6)
s) Satucharomyces cerevisiae (S, cerev
i-siae) (ATCC, 2341, and 28
7) Satucharomyces salmon (S, 5ake) (A
TCC, 4134) <Sake yeast> Satucharomyces iripsoideus (S, e l l 1 pso 1 derbs) (
Wine yeast〉Yaccharomyces formosensis (S, formosensis) (alcohol fermentation from molasses) Satucharomyces labalom (S, uvαr) (A
TCC, 2345) <Berer yeast bottom yea
st〉S. rouxi
i) (ATCC, 2615) <L fermented in oil>C
) Pichia (pichia) Pichia memplanafaciens (p, membra,
-nafaciens) (ATCC, 2085) <Serial yeast (fumarase self-control)> d) Hansenula %, '(Hansenula) Hansenula anomal (H, αnomalα) (ATCC, 58
0) <Membrane yeast (tryptophan synthesis)> e) L7 (e-1) Kluyveromysis ph, (Kluyve
romyces) Curveromysis - Frazi! J Su(
K, fr (Lrti-1is) (ATCC18554)
<Alcoholic fermentation (from lactose), lactase synthesis> Curveromysis lactis (K, 1actis) (
ATCC, 2628) <Alcoholic fermentation (from lactose), lactase synthesis> (g-2) Debayomyces machinakae bar y
omy-ces) Thebayomyces hansenii (D, hansenii)
Riboflavin synthesis, (e73) Ribomyces, (Lipomyces
) Lipomyces starkeyi (L, 5tarkeyi)
(A'I'CC, 12659) <oleaginous yeast> Lipomyces lipoferus (■,, 1ipo-feru8>
A'I'CC, 32031) <oleaginous yeast> (e-4) Endo-mycopsis
) Endomycopygis myfricella (E, fi-bul
igera ) (ATCC, 2080) <t,, Stinging yeast (from starch), Curcoa mirror self-produced> (e-5) Ashby 7ka (AShbyα) Ashbya gossypii <Aogossypii) (ATC
C, 10895) <:”j yK75 i y@, 5
M>(g-5)xramosecium% (Eremothe
-cium) Elamothesium ashby (F;, ash, byi
i) <Ribofuramine synthesis> (B) Asporous yeast (a) Candida utilis (C, utilis) (ATCC, 9226) <
Feed fermentation @: (!lj from sulfuric acid pulp waste liquid) Inosinic acid raw material> Canteda tropicalis ((:, tropicalis)
is ) (ATCC, 1369) <Feed yeast (from n-paraffin)> Candeda lipolyteica (C, l ipo ly, ti
ca) (ATCC, 8661) <1=4 yeast (n-
(from paraffin)〉 (b) Torrblopsis Torrblopsis (T, υersa t i -1
is) (ATCC, 20222) <Post-ripening of brewed foods> Turkishpisis candida ('l', c and i
d a) (ATCC, 10539) <Transfer of brewed foods-> Turkopissis hormy ('l', h o 1
mi 1) (ATCC, 22034) <Bread production>
Turkishpisis glabrata (T, glabrata
) (ATCC, 15126) <Alcohol production> (C)
Rhodotorula paulownia (R, gluti-1zis) (A
TCC-15125) <Fat storage in the bacterial body, carotenoid 6> (d) Other non-sporulating yeast'd-1 Cryptococcal force/Jj4 (Crypt oc
o -ccus) Cryptococcus laurentii (C=, lαU-re
ntii) (ATCC, 18803) <Production of lysine (
(from Amitsukafloractam)> Among the above yeasts, yeasts belonging to the genus Satucharomyces, Curveromyces, and Cryptococcus are preferred.

In addition, antibiotics produced by microorganisms such as those mentioned above are broadly divided into those produced within the body and those produced as metabolites. , invertase, glutathione, and cytochrome C produced by Satucharomyces he organisms; and carotenoids produced by microorganisms of the genus Rhodotorula. In addition, most microorganisms correspond to the types of substances produced as metabolic substances, such as penicillins and cephalosporins produced by fungi such as Penicillium genus and Cephalosporium; Streptomyces metabolites produced by actinomycetes such as the genus Bacillus and genus Nocardia; Contains metabolites, etc.

The method of the invention is generally effective for the production of Kanamai/and streptomycin by microorganisms of the genus Streptomyces; the production of penicillin G by microorganisms of the genus Penicillium; and the production of cephalosporin C by microorganisms of the genus Cephalosporium.

The cultivation of the antibiotic substance-producing microorganism according to the method of the present invention is carried out at least 34 Q nm or less, preferably 35 Q nm or less.
The treatment is carried out under irradiation with light substantially free of ultraviolet rays having a wavelength of Q nm or less, more preferably 380 nm or less.

In this specification, the expression "') (light rays that do not substantially contain ultraviolet rays below nm)" preferably refers to rays that contain no ultraviolet rays below X nm by 11100%, but This means that there is no problem even if ultraviolet rays of X nm or less are present in a small amount that does not adversely affect the culture of the present invention.

Conventionally, the industrial production of antibiotics by fermentation has usually been carried out in dark tanks under conditions that substantially avoid exposure to light.

In contrast to such conventional fermentative production methods for antibiotics, the present invention involves culturing microorganisms while actively irradiating them with light that does not contain the ultraviolet rays determined above.
The method of the present invention is essentially different from conventional fermentation methods.

There is no particular restriction on the light beam that can be irradiated, as long as it does not substantially contain ultraviolet rays with a wavelength of at least 34 Q nm or less,
Not only natural light but also artificial light can be used as long as it contains light with a wavelength in the visible light range.

Therefore, in culturing under natural light irradiation, the transmission of ultraviolet light with a wavelength of at least 340 nm or less in natural light is blocked by at least 90%, preferably 95% or more, 7 and more preferably 98 to 100%. On the other hand, when using artificial light, using a light filter as necessary, it is desirable to culture under light quality conditions of at least 340
A beam of unnecessary ultraviolet light with a wavelength of nrn or less is 100 μw
/3" or more, preferably 50μu) /an
It is preferable to culture under artificial light irradiation suppressed to 2 or less, more preferably 25 to 0 μW/cm 2 .

On the other hand, the light beam having a wavelength in the visible light range may be any of white light, polychromatic light, and monochromatic light, but at least 311
1. It is desirable to contain light rays with a concave wavelength in the range of 30 nm to 770 nm. Here, the visible light region is approximately 3
It means light within the wavelength range of 8Q nm to about 77Q nm.

According to the method of the present invention, the illuminance of the light beam irradiated onto the microorganism culture system is not strictly limited, but depends on the type of microorganism to be cultured, other culture conditions, etc.
Although the optimal irradiation conditions in each case can be easily determined by those skilled in the art through small-scale experiments, in general, the illuminance of visible light with a wavelength in the range of 380 μm to 770 nm is l Q Lux ~20,000L
uZ % preferably 50Luz ~10. QOOLuz
, more preferably 100 Lux to 5,00'OL
It is advantageous to emit a beam of light that is adjusted within the ux range. In addition, it is preferable that the ultraviolet rays in the wavelength range of 340 μm to 380 nm are not very strong, and the intensity of the ultraviolet rays in this wavelength range is generally 1000 μW/cr++2 or less, preferably 500 μW/cnt2 or less, and more preferably 300 μW/cTn2 or less. It is desirable to do so.

Further, according to the method of the present invention, a specific method of actively irradiating the microorganism culture system with the specific light beam is as follows:
For example, in a room (in a tank) that is substantially sealed from external light, it is possible to carry out measurements of at least 340 nm, η and below; Artificial light refers to light that does not substantially contain light in the wavelength range and has a wavelength within the visible light range [In this case, the artificial light source itself may emit light with such light quality characteristics. , or the artificial light source may be covered with a suitable filter so that the emitted light has the above-mentioned light quality characteristics]; under irradiation by the sun or natural light,
A transparent colorless to amber organic or inorganic coating material that substantially blocks the transmission of light in the wavelength range of Q nm and below, preferably 36 Q nm and below, more preferably 380 nm and below. (for example, a synthetic resin film containing an ultraviolet absorber).
- a method of carrying out; and a combination of both of the above methods.

The cultivation of antibiotic-producing microorganisms according to the method of the present invention can be carried out under exactly the same conditions as those conventionally used, except for the condition that it is carried out under irradiation with the above-mentioned specific light rays. For example, this can be carried out by culturing antibiotic-producing microorganisms in a suitable nutrient medium in liquid or solid state.

The nutrient source, nitrogen source, inorganic salts, etc. of the culture medium at that time are changed and selected as appropriate depending on the microorganisms and culture method used.
Those commonly used for culturing microorganisms are widely used.

The carbon source may be any assimilable carbon compound, such as glucose, sucrose, lactose, maltose, pI! I powder, dextrin, molasses, glycerin, etc. are used.

As a nitrogen source, any usable crab compounds are sufficient, such as cornstarch liquor, soybean flour, cottonseed oil, wheat gluten, babutone, butcher nose, yeast extract, etc.
Yeast, casein hydrolyzate, ammonium salts, nitrates, etc. are used. As other inorganic salts, for example, salts such as phosphate, magnesium, calcium, potassium, sodium, zinc, iron, manganese, etc. are used depending on the thickness.

The culture temperature and culture time vary somewhat depending on the microorganism used, and can be changed as appropriate within a range that allows the microorganism to grow sufficiently. In the case of filamentous fungi, yeast fungi, and basidiomycetes, the temperature is approximately 26°C, and in the case of actinomycetes, the temperature is approximately 30-30°C.
It is preferable to culture at about 5°C.

Historically, specific culture conditions vary depending on individual microorganisms; for example, the production of kanamycin, streptomycin, and penicillin is described in the 7th revised Japanese Pharmacopoeia, Part 1 [edited and published by Nankodo Co., Ltd., April 1966. Issued on the 15th], pages 1371, 679-680, and 1154-11
The production of cephalosporins can be carried out using the culture conditions disclosed in British Patent No. 745208, for example. can.

According to the method of the present invention described above, in the production of antibiotics by fermentation method, by culturing microorganisms under specific light quality conditions, the production of antibiotics is greatly promoted, which is useful in the fields of medicine, food, etc. The contributions made are extremely significant.

Next, the present invention will be further explained with reference to Examples.

Examples 1-6. Comparative Examples 1-2 Streptomyces kanamyces (1,F, 0°18
414) A culture pond having the composition shown in Table 1 was prepared. After sterilization, dry heat sterilized Petri dishes (90n)
rmφ) in 20d portions aseptically. Assimilate this agar medium (inoculate about 1 mm3 of hyphae of this fungus aseptically in the center of a Petri dish.

Visible light lamp (Toshiba fluorescent lamp FL-4osW; 40W
) and one near-UV lamp (Toshiba Blacklight Fluorescent Lamp FL-40SBLB; 40W) were set at a height of 20 Crn and 40 α from the medium surface, and continuous irradiation and extinguishment were repeated in a 12-hour cycle. . The above-mentioned bird dish inoculated with this threshold was further wrapped in a film-like light quality filter, and exposed to near ultraviolet and visible light irradiation equipment at 26°C ± 1°C.
The cells were cultured for 22 days under temperature control at ℃. The attached Fig. 1 shows the transmittance of each light quality filter by wavelength.

Table 1 After culturing, 20 g of distilled water was added to each Petri dish, the agar was ground to a size of about tm3, and the agar was left at room temperature for 5 hours. The above solution containing agar particles was filtered using filter paper (1'he T
op Filter Paper J, 2: Tc
yyanShoji Co, l! ! Filter with 1/
% dark-colored P solution 16-18〃I was obtained. Furthermore, a membrane filter (1'M-8. Porecyme valve φ; T, oy
o Roshi Co.

The P solution was re-filtered using a filter (manufactured by M. Co., Ltd.) to obtain 1 volume of a transparent amber-colored solution. These solutions were analyzed using a Shimadzu-DuPont high-performance liquid chromatography model LC-880 to obtain a liquid phase of 0.1 mol K.
H2PO4, column: Shimadzu-DuPont AAXLO6,8
809514082, 1st printing φxioo.

Chu, flow rate: 0-41 me/'rn Z n
-, Injection amount: 12 μt 1 pressure crab 52 Kf/cr1
1 column temperature 1t: room temperature, R1 detector: 5ILodex
The analysis was carried out under the conditions of RI Model SE-11. The analysis results are shown in Table-2.

According to Table 2, the amount of kanamycin produced in the Example was increased by about 90% compared to Comparative 91J.

Table 2 Production index: The production amount of Comparative Example 2 (dark area) was set as 100.

To Examples 6 to 9 and Comparative Example 3-4 Laboratory stock of Streptomyces canamayticus (1,F, stock from 0°13414) was batched in a jar fermenter with a capacity of 2.5 cultured in a formal manner.

Fermentation parameters are as follows. pH 68; Temperature 27°C; Impeller speed 820 revolutions/min; Impeller diameter 701
111+1: 6 rotary blade desk turbine blades; air flow 1.011 min. For foaming, use polypropylene 2 as needed.
025 [BDti Chemical Co., Ltd.
o,) Poulet, Dorset] was suppressed. The same culture medium composition as in Table 1 was used.

The medium used was 1 and 2 tons each. Air was introduced from below the impeller and mixing was aided by four buckles located vertically around the culture jet vessel.

A light quality filter is attached to the entire outside of the Pyrex glass tank wall, and a visible light lamp (Toshiba fluorescent lamp FL-40SW; 4
0W) near ultraviolet lamp (Toshiba Blacklight Fluorescent Lamp FL-40SB) at a distance of 40 cIn from the other side.
One LB; 40S'S/) tube was attached and cultured in a continuous irradiation section and a dark section.

After 96 hours of culture, the culture of each light quality area was transferred to p paper (
The Top Filter Paper
) f6.2; Toppan 5 (manufactured by HojiCo) and further membrane filter (TM-8,
Pore size 0.8μφ, TOYORO8HICo, LT
A transparent amber-colored culture solution was obtained by suctioning the culture solution (manufactured by D., Ltd.).

These P liquids (1 t each) were mixed with a cationic modification resin (Ayn
berlite I RC-50) column.
It was allowed to flow for 1 minute to adsorb kanamycin. then 5
Rinse with 00 n of distilled water and add 50 n of lN-HCl.
0 mg was allowed to flow down the column for 20 minutes, and kanamycin hydrochloride was eluted and released. Add the eluate to 10%-# a OH
Adjust the pH to 7.5 with water and add Amber-1ite again.
It was allowed to flow down to 1RC-50 and adsorbed. Wash stage with distilled water, eluted again with 500 ml of HCl,
Furthermore, the pH was adjusted to 6.0 by passing it through Amberlite I R-4B. Add the eluate to 4 or
00m/! 500 m of methanol was added, and the temperature-pressure concentration was continued at 40C for a total period of 50 m
1. Closed. 500 mJ of acetone was added to this concentrated solution to obtain light brown powder crystals.

Table 3 shows the severity of kanamycin 74-hydrochloric acid fN after drying under reduced pressure.

Table 3 Production index: The raw # amount of the comparative example (dark area) was set as 100.

Examples 12-17. Comparative Examples 5-6 Streptomyces griseus (1, P', α1880
Table 4 shows the culture medium for 4). Adjusted the Onui stuff.

After sterilization, aseptically place 20
It was distributed in units of lre. After assimilation of this agar medium, a single spot of mycelium of Honzuke's 3rd grade was inoculated in the center of the Pel-IJ dish under aseptic conditions. Visible light lamp (Toshiba fluorescent lamp FL-40SW;
40W) and one near-UV lamp (Toshiba Blacklight Fluorescent Lamp FL-40SBLB; 40W) were set at a height of 201 yn and 4' Ocm from the medium surface, and the lights were continuously irradiated and turned off in a 12-hour cycle. repeated. The plate 1.9 inoculated with the above-mentioned real teeth was further wrapped in a film-like light quality filter, and heated under the near-ultraviolet and visible light irradiation equipment at a temperature of 26°C ± 1"C for 15 minutes.
Cultured for 1 day. The transmittance by wavelength of each light quality filter is
Shown in the figure.

Table 4 After culturing, 20ηi of distilled water was poured into each sticky dish, and the agar was ground into pieces of about 1+IO+13 in size, and left at room temperature for 5 hours. The above bath solution containing agar grains was placed on P paper.
2: ToyanShoji Co.
, amber-colored P solution 16-18 r,
I got qe. In addition, membrane filters (TM-g,
Bore size 0.3μφ; , TOYORoshiCo,
The P solution was filtered again using a commercially available product (manufactured by J.D. Co., Ltd.) to obtain a clear amber-colored solution.

These ljq liquids were analyzed using Shimadzu-DuPont high performance liquid chromatography LC-880 model, liquid phase: 0, 1 mot K.
H2PO4, column: Shimadzu-DuPont AAX Lot
, 830951408.21 period φ x 1000 mrn, flow rate: 0.41 ml / 77+, Z n % injection: 12 pL, pressure 2 Kf / cas Column temperature: room temperature, R1 detector: 5hodex RI M
It was analyzed using a second model of the Odel S E-11 model. The analysis results and the diameter of the soil at the mouth of the 9th day of cultivation were 6 (1j
The determined results are shown in Table 5.

-45- According to Table 5, the production of streptomycin was increased by about 50% in the Examples compared to the Comparative Examples.

In addition, regarding the growth of bacteria, it was found that the growth of bacteria was promoted in the ultraviolet-irradiated area.

Examples 18-22. Comparative Examples 7-8 Streptomyces griseus (1,F, 0°138
A 1-cell stock of the strain 04) was cultured in a batchwise manner in a 2.5-volume jar fermenter. Fermentation parameters are as follows. pH 6,8; temperature 2
7℃; impeller speed 820 revolutions/min; blade east diameter 70 degrees;
Rotating 4 disks per bin 6 blades; beam airflow 1. Ot/min.

For foaming, use polypropylene 2025 [8DH] as necessary.
Chemical Co., Poole, Dorset]. The composition of medium 4 was the same as in Table 4 except for the agar 209/l. The culture medium for one person was 1.2 tons each. Air was introduced from below the impeller, and mixing was aided by four baffles placed vertically around the culture vessel.

Pyrex glass mounting 1: Attach a light filter to the entire outside of the LJJ section, and use one rule 20 for fermentation.
A visible light lamp (Toshiba fluorescent lamp FL-) is installed at a distance of Crn.
40SW; 40W) near ultraviolet lamps (Toshiba Black Light Lamp FL-) at a distance of 40cm from one side of the curved blade.
40SBLB: 40W) was attached, and continuous irradiation and extinguishment were repeated in a 12-hour cycle. After culturing for 94 hours, transfer the culture fluid from each photogenic area to r paper (1'he To
p Filter Paper I6.2:Topp
filtered through a membrane filter (TM-8, pore size 0.8μφ, T
OYOll08HI Co, LXTD [)f Suction filtration was performed to obtain a transparent dark red culture medium. These furnace liquids (1 t each) were mixed with cationic exchangeable sealant (Amber-1).
1itel RC-50) column for 20 minutes to adsorb streptomycin. then 500p
It was washed with 1 liter of distilled water. l # -1IC1 of 5
00 ml was allowed to flow down the column for 20 minutes, and the streptomycin j was washed out. 16 effluent to lO%-N
Adjust the pH to 75 with αOH water and add Amberlit again.
e It was allowed to flow down to I RC-50 and adsorbed. After washing with distilled water, the pII was adjusted to 60 by bathing again with 500 tnl of 7V-HCl and passing through Amberlite I R-4B. 4 eluate
It was condensed to 100 inl at 0°C, 500rnl of methanol was added, and concentration under reduced pressure was continued at 40°C to bring the total volume to 50 ml. Add 50'rrI to this concentrate.
7! of acetone to obtain light brown powdery crystals. The weights of these streptomycin hydrochloride salts after drying under reduced pressure are shown in Table 6.

Table 6 Production index: The production amount of the comparative example (dark area) was set as 100.

Examples 17-20, Comparative Examples 9-10 Penicillium chrysogenum (1, P', 0.9252
) was prepared with the composition shown in Table 7.

After sterilization, separately sterilized Petri dish + 90 mmφ)
Aseptically dispensed 20me each. After assimilation of the agar medium, about 1 mm3 of mycelia of this bacterium was aseptically inoculated at a single point in the center of the Petri dish. Visible light amplifier (Toshiba fluorescent lamp FL-
40SW", 40W) and two near-UV lamps (Toshiba Blacklight Fluorescent Lamp FL-40SBLB: 40W)
One lamp was set at a height of 20α and 40cm above the surface of the melt, and continuous irradiation and extinguishment were repeated in a 12-hour cycle. The Petri dish inoculated with the above-mentioned main carp was further wrapped in a film-like light quality filter, and cultured for 22 days using the near-ultraviolet rays and bow line irradiation device with temperature control at 26°C ± 1'C. The transmittance by wavelength of each light quality filter is -A1
Shown in the figure. After culturing, each plate was placed in an IJ dish (fC
20tnl! of distilled water was added to crush one sphere to a size of about h-, and the mixture was left at room temperature for 5 hours. The above solution containing agar particles was coated on P paper (The Top Filter Paper).
A2: Toppan 5hoji Co.
The mixture was filtered through a filtrate (manufactured by Nippon Steel & Co., Ltd.) to obtain an amber colored liquid mixture.

These solutions were added to Shimadzu-DuPont AAXLot.

8LO95140B=2.1mmφX1000m+, flow rate: 0°41 nf/m@nv injection i: 12μt
, pressure crab 52 Kp/cr! l + Column temperature: Chamber (B, UV detector: Shimadzu UV20L type, wavelength 254n
The analysis was carried out under conditions of m. The analysis results are shown in Table-8.

Table 7 Magnesium sulfate heptahydrate 0.5t According to Table 8, the production amount of penicillins was increased by about 70% in the examples compared to the comparative examples.

Table 8 Production index: Comparative example (dark area) production, 1' (f-to
o and Examples 29-33. Comparative Examples 11-12 Penicillium chrysogenum (1,F, 0.9252
A laboratory stock of a strain obtained from a commercially available strain was cultured in a jar fermenter at Z, szgt.

Fermentation parameters are as follows. pH 6,8; Height 7℃; Impeller speed 820 revolutions/min; Impeller diameter 70
rran: rotary blade desk turbine 6 blades; desired air flow 1.011 minutes. For foaming, use Po.1) Propylene 2025 [BDH Chemical/lz Co., Ltd. (ChemicalC
o, ), Poulet, Dorset]. The medium composition used was the one shown in Table 7 except that 20 tons of agar was removed. The amount of medium in each fermentor is 1.2
It was set as t. Air was introduced through the blades of the impeller, and mixing was aided by four vertically positioned baffles around the culture vessel.

A light filter was attached to the entire outside of the Pyrex glass fermenter wall, and the fermenter piece was 111,120 cm long.
At a distance of
W: 40W) 2 near ultraviolet lamps (next summer blacklight fluorescent lamp FL-
40SBL, B: 40W) was attached, and continuous irradiation and extinguishment were repeated in a 12-hour cycle. 116 hour culture 1
Spread the culture solution of each optical zone on paper (The I'op).
Filter Paper JK 2: Toppan
Filter with a membrane filter (TM-8, pore size 0.8μφ, TO
YORO8I-11Co, #! ) to obtain a clear amber culture solution. These p liquids (each ig) were mixed with anion type ion exchange resin (DIAION-8A
-208) for about 10 minutes to adsorb the cephalosporin compound. Then, it was washed with 1 liter of distilled water. Further, it was eluted with 100 ++/diluted sulfuric acid water of pH 4.9, and 50. d methanol was added, and the total volume was reduced to 5 ml using a rotary evaporator at 40°C.
It was a@ until 0 ml.

Add 450 ml of ethanol to 50 rnl of each 6 sample solution.
In addition, light brown powdery pickled wood was obtained. Table 9 shows the stacking of these i, fl 1 crystals after drying under reduced pressure. Also, the ancestor of these, the 1st crystal. R, when I took the chart, 2.95, 3.28, 3.85, 3.40° 5.68, 5.68, 5.99, 6.20, 6
．． 70.

6.88, 7.06, 7.15, 7.48, 7.5B.

7.97, 8.20.8.60.8.80, 9.06°9.26, 9.70.9.90, 10.7, 11
．． 1.

There were absorption peaks at 12.2, 13°l, 13.6, 14.8, and 15.0μ, which confirmed that it was a penicillin G compound.

Table 9 Production index: The production amount of the comparative example (dark area) was set as 100.

Examples 24-28, Comparative Examples 13-14 Cephalosporium l I, F, 0.30053)
As a medium for this purpose, a medium having the composition Table-1O was investigated. After sterilization, a Petri dish (90 mm
) were aseptically distributed in 20 ml portions. After assimilation of the agar medium, about 1 DII and 113 hyphae of this I cellulose were aseptically inoculated in the center of a vetri dish. Two bright vision lamps (Next Summer Fluorescent Lamp FL-40SW; 40W) and a near ultraviolet lamp (Next Summer Black Light L-Fluorescent Lamp FL-40SBL)
B: One 4014"l bottle was set at a height of 20 cm and 40 cm from the surface of the medium, and continuous irradiation and clarification were performed in a 12-hour cycle. The cells were collected.

The above-mentioned veterinary dish inoculated with the main seedlings was further wrapped in a film-like light quality filter and cultured for 25 days at 26°C±1°C under the near-ultraviolet, i] line of sight irradiation device.

The transmittance by wavelength of each light quality filter is shown in Fig.-1.

Table-10 Medium Composition (Medium 12) After culturing, 20ml of distilled water was added to each vietnamese within 1 month, and the agar was ground to a size of about Lm' and left at room temperature for 5 hours. The above solution containing agar grains was added to Di1-11 (The T
op Filter Paper tK, 2
:ToppanShoji Co, ,q)
! F, ifi was applied to obtain an amber color pH 6-18.

In addition, membrane filter (TM-8, pore size 0)
．． 8μφ: manufactured by TOYORO8HICO0) to add p liquid,
Refiltration was performed to obtain a clear amber solution. These 1δ liquids were processed using high-performance liquid chromatography L
C-880 type, liquid phase:, 0.1 mol KH, PO
4, Column: Takashi-Dubo 7AAX LOL, 880
951408. Between 2 and 1 φX 1000 hrms Flow rate 20, 41 rnl! / Wl, @ns injection amount:
12pt, pressure 52Kp/crl - Column temperature: room temperature,
UV detector: Takashi UV2014, wavelength 25: 4 nm
The results of 5 analyzes conducted under liquid chromatography conditions and the results of measuring colony sizes after 25 days of culture are shown in Tab 4g-2.

As shown in Table 2, in the real sister case, cephalosporin C yield increased by about 70% compared to the conventional method. Regarding the growth of one bacterium, there was no significant difference between the test plots.

Examples 40-42. Comparative Examples 15-16 Cephalosporium sp. (1,F, 00fl1
0058) laboratory stock of 2.51
'4 It was cultured in batches in the jar fermenter shown in the figure. Fermentation parameters are as follows. pH6,8
: Temperature 27°C; Impeller speed 820 revolutions/min; Impeller diameter 70 mm; Rotary blade desk turbine 6 blades; Air flow LO
11 minutes. For foaming, use polypropylene 2025 as needed.
[, BDH'i Chemical Co.
), Poulet, Dorset]. The culture medium composition is shown in Table-12. The amount of culture medium for 1 history is 1.2 each
It was set as t.

Table 12 A light quality filter was attached to the entire outside of the wall of the Pyrex fermenter, and two visible light lamps (Next Summer Fluorescent Lamp FL-4osW: 40W) were installed at a distance of 20 crn4 on one side of the fermenter, and at a distance of 40 crn on the other side. Near ultraviolet lamp (next summer black light fluorescent lamp FL-408BLB', 40
W) One tube was attached and cultured in a continuous irradiation section and a dark section. The air was introduced from below the impeller and mixing was aided by four buckles placed vertically around the culture vessel. After culturing for 120 hours, the culture solution of each photoplast was incubated with fpi (The Top' Fir ter P).
aper A2: ToppanShoji Co.
0g) and then a membrane filter (TM
-8, bore size 0.3μφ, TOYORO8III
Suction filtration was performed using Co, LTD, [) to obtain a transparent amber colored culture medium, 4 liquids. These p liquids (each lt) were treated with anion type ion exchange resin (DIAION-8A-20B).
) for about 10 minutes to form a cephalosporin compound.
+/)k was adsorbed, and then washed with lt of distilled water. Furthermore, it was liberated with 100+m of dilute acid-resistant water with p II 4.9, and 50+m of methanol was added to these liberated liquids.
Heat the whole body to 50+i in a rotary evaporator at 40℃.
It has shrunk to . Each sample J solution 50' +, tl
(450 ml of /Cx Ri/-ru f: was added to obtain light brown powdery crystals. The weights of these crude crystals after drying under reduced pressure are shown in Table 4. 1.R
, I took the chart and found that it was 2.94μ, 3.06μ,
5.77μ, 6.05μ, 6.29μ, 657μ, 7
There were absorption peaks at 17μ and 736μ, confirming that it was mostly a cephalosporin C compound.

Table 13 Reference example Light quality filters &1 to 7 used in the above examples and comparative examples
was adjusted as follows.

Filter Kl: 100 parts by weight of polyvinyl chloride, dioctyl phthalate L/-
) (oJ'4 punishment) 4s tonne part, dibutyl base malate (thermally stable 41J) 1.5 parts, lead stearate (heat stabilizer) 1.0 parts by weight, stearin 1 part (lubricant)'
1. If part, and sorbitan monolaurate (
The 1O heavy acid portion (stain-proof property) was thoroughly mixed with each other, and the mixture was melt-extruded at 200° C. using an extruder to obtain a clear filter with a thickness of 0.075 nm.

This is called filter y%, 1.

In the formulation of the above filter, 461, further 2-
The above filter A1 except that 1.6 parts by weight of hydroxy-4-methoxybenzophenone (ultraviolet absorber) was added.
A filter with a thickness of 0.075+la was obtained by using the same method as in 4. This is called Filter Haruka 2.

Filterano b3: In the above filter notification 2, 2- which is an ultraviolet absorber
Hydroxy-4-methoxybenzophenone
A filter having a thickness of 0.11+ill+ was obtained in the same manner as in Filter No. 2 above, except that 15 parts by weight of rtbutylphenylpenztriazole was used. This filter is called No.I6.3.

Filter flat panel 4: Two sheets of commercially available yellow colored cellophane (thickness o, oismm) were superimposed on the filter A8 to obtain a yellow colored filter. This is called filter 16.4.

Filter flat plate 5: Two sheets of commercially available blue colored cellophane (thickness o, 018 mm) were superimposed on the filter A3 to obtain a blue colored filter. This is called filter 16.5.

A green colored filter was obtained by superimposing two commercially available green color filters (thickness o, ots+m) on the above filter 1 and 8. This filter is called filter I6.6.

Filter No. 167: Commercially available red cellophane (thickness 0.
A red layer color filter was obtained by stacking two sheets of 018 mm l. This is called filter boiling 7.

The light transmittance curve of the above filter Al~7 is shown in the attached 1st page.
As shown in the figure.

[Brief explanation of drawings]

Figure '41 shows the filter Al- used in the Examples and Comparative Examples.
It is a figure of the light transmission curve by wavelength of filter Haruka 7. Continuing from page 1 CI2 R1/465) 0 Inventor Yoshiyuki Yokomizo 1-9-11 Shinkaneya-cho, Uozu City Seiwa Proceedings Amended Security Ceremony) October 20, 1981 Patent Section Chief' @ Kazuo Wakasugi Tono 1, of the incident Display corner L151F'+4 total 111IIi103906 No. 2
, Name of the invention Relationship with the Nagisa case in which the productivity of antibiotics is amended as above 1m3 Amendment Patent applicant address 3J-3T+FT No. 4, Marunouchi, Chiyoda-ku, HigashiyA, Agent Address: 107 □1 .11 5 Date of amendment order: September 28, 1982 (shipment date) 6, Specification subject to amendment 7, Table of contents of amendment l After culturing, add 20-ml of distilled water in a separate Petri dish. In addition, crush the agar to a size of about 1 m'. It was left at room temperature for 5 hours. Table 2 Production index of the above agar grain-containing solution: The production amount of Comparative Example 2 (dark area) was set at 100. Examples 6-9. Comparative Examples 3-4 Streptomyces kanamaiticus (I, yO11
3414) was brought to pH 6 by patch method in a 2.51 capacity jar fermenter.
．． 811 was adjusted to 0. The eluate was concentrated to 100°C at 40°C, 500ml of methanol was added, and the eluate was further concentrated at 40°C.
Concentration under reduced pressure was continued at 50°C, and the whole was closed at 50°C. Add 500 tn1. to this concentrate. of acetone was added to obtain light brown powder crystals. The weights of these kanamycin A-hydrochloride salts after drying under reduced pressure are shown in Table 3. Table 3 Production index: The production amount of the comparative example (dark area) was set as 100. Table 4 After culturing, 20-mL distilled water was added to each Petri dish and the agar was crushed to a size of about 1 mm. It was left at room temperature for 5 hours.
l'he Top Filter Paper Ji
2: Toppanl,.・Amber-colored F liquid 16
~18- was obtained. In addition, membrane filter (TM-
3, Pore size 0.3μφH1'OYORoshiN
-45- Table 6 Production index: The production machine of the comparative example (@Kuro-ku) was set as 100. Examples 17-20, Comparison 9119-1O Henicillium.
A culture medium for clear 1'fum (I, P', 0.92s2) having the composition shown in Table 7 was prepared. Sterilized, separately sterilized Petri dish (90+wφ)
20 pieces of leprosy were distributed to each patient. Solidification of this fire-like medium
In terms of Vjp, approximately 1111111" of hyphae of this fungus
0951403,! 1mmφxlo00m, flow rate: 0
．． 41*j! /ηtin, injection amount: 12 μt 1 pressure crab 5
The analysis was performed under the following conditions: 2 Kt/ad, column temperature p[: room temperature, UV detector: Takashi UV201 model, wavelength 254 nm. The analysis results are shown in Table-8. Table 7 According to Table 8, in the example, compared to the comparative example, about 7
We saw an increase in the production of penicillins. Table 8 Table 9 Production index: The production index of the comparative example (Angu Ward) was set as 100. Examples 24-28% Comparative Examples 13-14 A culture medium for Cephalosporium (1,F, 0.30053) having a composition of 7゛αble-10 was prepared. After sterilization, it is a sterilized dish (90mm diameter).
) was aseptically distributed in 20-minute doses. After solidification of this agar medium, a single point of mycelium of this bacterium of approximately 1 sa" was inoculated in the center of a Petri dish using a sterile method.
L-40S&V, 40W) 2 near-UV lamps (black light fluorescent lamp FL-4oSBLHH4o next summer)
W) 1 tube and 40 cnl each from the surface of the medium.
Set it to the crystal level. Continuous irradiation and smoke removal were repeated in a 12-hour cycle. The above-mentioned veterinary till inoculated with the present bacteria was further wrapped in a film-like light quality filter and cultured for 25 days at 26T, ±1C under the near ultraviolet and visible light irradiation equipment. The transmittance by wavelength of each light quality filter is shown in Fig.-1. 1'abltt -10% soil composition (in medium it) -59
- Table 12: Attach a light quality filter to the entire outside of the wall of a Pyrex fermenter, and install two visible light rande (next summer fluorescent lande FL-40SWg40W) at a distance of 20 cfn on one side of one fermenter, and at a distance of 40 cfn on the other side. Near ultraviolet lamp (next summer black light fluorescent lamp PL-405RLB l 4 Q
W') One tube was attached and cultured for 5 consecutive days in both the irradiated area and the dark area. Air was introduced from below the impeller, and mixing was aided by four baffles placed vertically around the culture vessel.
μ, 5.77μ, 6.05μ, 6.29μ, 6.57μ
There were absorption peaks at , 7.17μ, and 7.36μ, confirming that it was a cephalosporin C compound. Table 13 Production index: The fresh weight of the comparative example (dark area) was set to 100. Reference Example Light quality filters 41 to 7 used in the above Examples and Comparative Examples
was adjusted as follows. Filter store: 1 part of polyvinyl chloride 100ηi, 45 parts of dioctyl phthalate (plasticizer), 1.5 parts of dibutyltin malate (thermal stabilizer), 1 part of zinc stearate (thermal stabilizer). OmL Iibe, stearic acid (lubricant) o, t3
1g part, and sorbitan monolaurate (antifogging) 1
．． The 0'Nit parts were thoroughly mixed with each other, and the mixture was melt-extruded using an extruder at 200C to a thickness of 0.
A transparent filter of 075111111 was obtained. This is called filter boiling 1. Filter Shop 2: In addition, in the formulation of the above filter A1. Except for blending 1.6 parts by weight of 2-hydroxy-4-methoxybenzophenone (external ray absorber), yfl, length 0.075 mm was prepared in the same manner as in the above filter flat 1.
obtained a filter. This is called filter I&2. 3 to filter J: In the filter 42, 2- which is an ultraviolet absorber
Hydroxy-4-methoxybenzophenone 1.6'ii
The amount of 2-(2'-hydroxy-3'-methyl-5'-
tart butylphenyl)benzotriazole 1.5
A filter with a thickness of 0.1-1 was obtained in the same manner as in the filter A2 above, except that the lid part changed to a heavy lid part. This filter is called A3. Filter I64: Two sheets of commercially available yellow colored cellophane (thickness o, Olgm) were superimposed on the filter A3 to obtain a yellow colored cellophane. This is called filter A4. Bu. Two sheets of commercially available blue colored cellophane (thickness: 0.018 am) were superimposed on the above filter/I63 to obtain a blue colored filter. This is called filter A5. Filter A6: Two sheets of commercially available green cellophane (thickness 0.018 s*) were superimposed on the upper Nj2 filter A3 to obtain a green colored filter. This is called filter A;6. Commercially available red cellophane (H 0.
A red colored filter was obtained by stacking two sheets of 0181111117. This is called filter A7. The light transmittance curve of the above filter At~7 is shown in the attached 1st
As shown in the figure. 4. Brief explanation of the drawings Figure 1 shows the 7'C filter Al used in the examples and comparative examples.
~ Diagram of the wavelength-specific light transmission curve of filter 47, ah.
1.・1

Claims (1)

[Claims] 1. A method for culturing antibiotic-producing microorganisms and recovering antibiotics from the culture, wherein the culture is
A method for improving the productivity of antibiotics, characterized in that the method is carried out under irradiation with light that does not substantially contain ultraviolet rays having a wavelength of 40 nm or less. 2. The method according to claim 1, wherein the culturing is carried out under irradiation with light that does not substantially contain ultraviolet rays having a wavelength of at least 380 nm or less. 3. The method according to claim 1, wherein the light beam contains light having a wavelength within the visible light range. 48 sets of light rays substantially eliminate ultraviolet rays with a wavelength of at least 34 Q nm or less, or at least 340 Q nm.
2. The method according to claim 1, wherein the artificial light is substantially free of ultraviolet rays with wavelengths of nm or less and contains light rays with wavelengths within the visible light range. 5. The light beam is at least 380 nm to 770 nrn
The first claim containing radiation of wavelength within the range of
The method described in section. 6. The illuminance of the visible light range within the range of 380 nm to 77Qnm is 10Laz to 20.000 Lux.
The method according to claim 1, which is within the scope of. 7. The method according to claim 1, wherein the antibiotic-producing microorganism is a mold or an actinomycete. 8. The method according to claim 1, wherein the antibiotic-producing microorganism is a kanamycin-, streptomycin-, penicillin-, or cephalosporin-producing microorganism. 9. The antibiotic-producing microorganism is Streptomyces (
Streptomyces) genus, Penicillium (p
9. The method according to claim 8, wherein the microorganism is a microorganism belonging to the genus Enicillium or the genus Cephalosporium.