JP3029329B2 - Method for producing optically active 1,3-butanediol - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing optically active 1,3-butanediol useful for producing various pharmaceuticals such as antibiotics.

[0002]

2. Description of the Related Art As a method for producing optically active 1,3-butanediol, a racemate of chemically synthesized 1,3-butanediol is optically converted using an optical resolving agent. Division method (Japanese Patent Laid-Open No. 61-1916)
No. 31), using a Raney nickel catalyst treated with an optically active compound to convert 4-hydroxy-2-butanone to
A method for asymmetric synthesis of 3-butanediol
204187 and Bull. Chem. Soc. Jpn., 53,
1356-1360 (1980)]. But,
These methods all require the use of expensive optical resolving agents and catalysts. In particular, in the latter method, the optical purity of the product is low. Therefore, in these methods, it is difficult to obtain optically active 1,3-butanediol having high optical purity by an economical and simple method.

On the other hand, the present inventors have made a microorganism having the ability to asymmetrically assimilate the above-mentioned mixture to act on an inexpensive mixture of 1,3-butanediol enantiomers, and to obtain the remaining optically active 1,3-butanediol. A method for collecting butanediol (International Publication No. WO89 / 10410), a method similar to
S (±) -1,3-butanediol to (R) -1,3
-Method for producing butanediol (Japanese Patent Laid-Open No. 1-3209)
No. 97 gazette). According to these methods, optically active 1,3-butanediol having high optical purity can be easily and industrially produced.

Further, the present inventors have proposed a method of allowing a microorganism to act on an enantiomeric mixture of 1,3-butanediol in the presence of an alcohol and ketol (Japanese Patent Application No. 2-34249). According to this method, it is possible to increase the ability of the microorganism to asymically assimilate and increase the residual amount of the optically active 1,3-butanediol.

The present invention is a further development of these techniques, and an object of the present invention is to provide a method for easily and efficiently industrially producing optically active 1,3-butanediol having high optical purity. It is in.

[0006]

In order to achieve the above object, the present inventors have conducted intensive studies and found that an enantiomeric mixture of 1,3-butanediol can asymmetrically assimilate the mixture in the presence of a zinc compound. The present inventors have found that the asymmetric assimilation ability of microorganisms is remarkably improved by the action of microorganisms having, and that optically active 1,3-butanediol having high optical purity remains selectively and efficiently, and the present invention has been completed. did.

[0007] That is, the present invention provides a method for producing a mixture of an enantiomer mixture of 1,3-butanediol and a microorganism having the ability to asymmetrically assimilate the mixture in the presence of 1 to 50 ppm of a zinc compound. To recover the remaining optically active 1,3-butanediol.
-A method for producing butanediol , wherein the microorganism is:
Geotrichum microorganism, Roderomyces
(Lodderomyces) microorganism, Candida
Microorganisms and the genus Kluyveromyces
Optical activity 1, which is at least one selected from microorganisms
Provided is a method for producing 3-butanediol .

The ratio of the R-form to the S-form in the enantiomer mixture of 1,3-butanediol is not particularly limited, but it is advantageous to use the racemic form from the viewpoint of economy.

The type of the microorganism is not particularly limited as long as it has the ability to asymmetrically assimilate an enantiomeric mixture of 1,3-butanediol. The microorganisms include
Microorganism of the genus Geotrichum, Roderomyces
(Lodderomyces) microorganism, Candida
Microorganisms and the genus Kluyveromyces
Microorganisms can be used.

[0010] Among the microorganisms, the S-form of 1,3-butanediol in the enantiomeric mixture is asymmetrically assimilated,
Examples of microorganisms having the ability to leave the R-form of 1,3-butanediol include the following microorganisms.

[0011] (1) gate Otorikamu (Geotrichum) a microorganism belonging to the genus:
G. candidum IFO 46
01, IFO 5767, IFO 5368, JCM
7395, G.rectang
ulatum) JCM 1750, Geotricum Clebany
(G.klebahnii) JCM 2171, G. fermentans JCM 2467, G.capitatum JCM 390
8. Geotricum Eriense JCM 3
912, etc. ( 2 ) Loderomyces microorganism: Roderomyces L. elongisporus IFO 1
1,3-butanedi in an enantiomeric mixture such as 676
These microorganisms selectively assimilate the S-form of oars.
At least one kind may be used, and even when used in combination with the following microorganisms:
Good. (3) Brevibacterium microorganisms:
Levibacterium iodinum (B.iodinum) IFO
Such as the 3558 (4) Candida (Candida) a microorganism belonging to the genus: Candida Le
C.rugosa IFO 1364, Candida Parap
C. parapsilosis IFO 0640, IFO
0708, IFO 1396, Candida salmon (Cs
ake) IFO 1981, Candida Santa Maria (Cs
antamariae) IFO 1982, Candida Shata
C.shatavii IFO 10258, Candida
Shehatae IFO 1983, Candy
C. stellata IFO 0703, Cande
C. tropicalis IFO 1400
Etc. (5) Enterobacter (Enterobacter) a microorganism belonging to the genus: Ente
E. cloacac ATCC 7256
(6) Klebsiella microorganism: Klebsiella
K. pneumoniae IFO 1201
9 and the like (7) Pseudomonas microorganism: P. diminuta IFO 1269
7 etc. (8) Rhodotorula microorganism: R. glutinis IFO 0395 etc. (9) Saccharomyces microorganism: S. cerevisiae AHU 34
02 etc. (10) Saccharomycopsis microorganism: S. lipolytica I
FO 1550, etc. (11) Microorganisms of the genus Sterigmatomyces: S. elviae DSM
70852, etc. (12) Microorganisms of the genus Trichosporon: T. cutaneum IFO 1198, T. capitatum IFO
The microorganisms (1) to (12) such as 0743 are disclosed in Japanese Patent Application Laid-Open No. 2-195897 of the applicant of the present invention.

(13) Aciculoconidi
um) Microorganism: Acycloconidium acreatum
(A. aculeatum) IFO 10124, etc. (14) Microorganisms of the genus Brettanomyces: B. anomalus IFO 07
96 etc. (15) Microorganisms of the genus Cochliobolus: C. miyabeanus IFO 663
1 etc. (16) Corynespora microorganisms: C. cassiicola IFO 6724, etc. (17) Dactylium microorganisms: D. dentroides ATCC 4603
2 etc. (18) Echinopodospora (Echinopodospora) microorganism: E. jamaicensis I
FO 9819, etc. (19) Hamigera genus microorganism: H. avellanea IFO 7721, etc. (20) Helminthosporium microorganism: Helminsosporium sigmodium valariity illegrare (H. avellanea) sigmoideum var. irregular
e) IFO 5273 etc. (21) Nectria microorganism: N. cinnabarina IFO 6821 etc. (22) Phyalocephala microorganism: P. bactrospora IFO
8770 and the like The microorganisms (13) to (22) are disclosed in Japanese Patent Application No. 1-325360 filed by the applicant of the present invention.

(23) Microorganisms of the genus Rhodococcus: R. erythropolis
DSM 43200, JCM 2893, R. rubropertinctus DSM
43346, R. rhodoc
hrous) JCM 2157, Rhodococcus equi (R. eq
ui) JCM 1311 etc. (24) Gordona (Gordona) microorganism: G. bronchialis JCM 3198 etc. (25) Streptomyces microorganism: Streptomyces netropsis HUT
No. 6068 and the like The microorganisms (23) to (25) are disclosed in Japanese Patent Application No. 2-276100 filed by the applicant of the present invention.

(26) Clavispora microorganisms:
C. Lusitaniae IFO
1019 etc. (27) Microorganisms of the genus Kloeckera: K. africana IFO 0869 etc. (28) Microorganisms of the genus Schizoblastosporion: S. kobaya
sii) IFO 1644 and the like The microorganisms (26) to (28) are disclosed in Japanese Patent Application No. 2-24185 filed by the applicant of the present invention.

Microorganisms that leave R-forms include those disclosed in JP-A-1-320997, such as those belonging to the genus Arthroascus, the genus Debaryomyces, and the genus Endomyces.
yces), Guilliermondella, Hansenula, Kluyvermyces
omyces), Pichia, Stefanoascus (S
genus tephanoascus), genus Trigonopsis,
Achromobacter genus, Agrobacterium genus, Bacillus genus, Cellulomonas genus, Citrobact
er), Corynebacterium, Escherlchia, Microbacterium (M
icrobacterium), Amauroascus
Genus, genus Arxlella, backusella
Genus, Botryotinia, Cephalosporlum, Circinella
Genus, genus Dicraranidion, genus Emericelopsis, Fusarium
Genus, Gibberella, Gloeophyllium (Glo
eophyllum, Laetparus, Pestalotia, Pholiota, Pleurotus, Rincoladeira
adiella), Rhizops, Synthephalasturum,
Also included are microorganisms belonging to the genus Tigosporium and the genus Gonglanera.

[0016]

Microorganisms capable of asymmetrically assimilating the R-form of 1,3-butanediol in an enantiomeric mixture and leaving the S-form of 1,3-butanediol as the microorganism include:
For example, the following microorganisms can be mentioned.

[0018] (1) key Yandida (Candida) a microorganism belonging to the genus: Candida-carry butt grayed Nicolas (C.cariosilignicola)
DSM 2148, Candida Kefil (Beijerinck) DSM 70073,
Candida Crusay (Castelani) (C.krusei
(Castellani)) DSM 70075, C. succiphila DSM 2149, C. utilis IFO 0639, IFO
0626, C. antarctica
ica) IFO 10182, Candida catenulata
(C. catenulata) IFO 0745, C. intermedia IFO 0761, C. maltosa IFO 1978, Candida Mogii IFO 0436, Candida Sudo Intermedia (C. pseudointermedia) I
FO 1693, C. curiosa
IFO 1336, C. diverrs
a) IFO 1091, Candida Ethelsy (Ce
tchellsii) IFO 10037, C. inconspicua IFO 0621, Candida lambica (C. lambica) IFO 1146, Candida methanolovescens IF
O 10402, Candida nitratohira (C.nit)
ratophila) IFO10300, Candida salmon (Cs
ake) IFO 1517, Candida salmanticensis IFO 10242, Candida silvatica IFO 10311,
Candida sorboxylosa IF
O 1578 etc. ( 2 ) Microorganisms of the genus Kluyveromyces (Kluyveromyces): K. drosophilarum
IFO 1012, Kluyveromyces Lactis
(K.lactis) such as IFO 1267, IFO 1903 et
R-form of 1,3-butanediol in a mixture of enantiomers
At least one of these microorganisms that selectively assimilate
It may be used in combination with the following microorganisms. (3) Agrobacterium microorganism: Ag
Lactobacillus radiobacter IF
O 12664, etc. (4) Microorganisms of the genus Azotobacter: Azotobacter
A. chroococcum IFO 129
94, etc. (5) Bacillus microorganism: Bacillus brevis
(B.brevis) IFO 3331, Bacillus cereus (Bc
ereus) AHU 1707, AHU 1355, Bacillus
・ B.sphaericus IFO 3525, IF
O 3341, B. subtilis IF
O 3007, IFO 3037, etc. (6) Microorganisms of the genus Brettanomyces: Breta
B. abstines DSM 70
726, etc. (7) Microorganisms of the genus Citrobacter: Citrobac
(8) Corynebacterium microorganisms such as C. freundii AHU 1534
Linecobacterium glutamicum (TC)
C 13032, Corynebacterium michiganens
(C. michiganense) IFO 13762, etc. (9) Microorganisms of the genus Dekkera: Dekkera burkisere
D. bruxellensis IFO 1590, etc. (10) Endomyces microorganism: Endomyces
(11) Microorganisms of the genus Erwinia: E. decipien IFO 0102, etc.
Carotobora Subspecies Carotobora (E.carotovor)
asub sp. carotovora) IFO 3830, etc. (12) Hansenula microorganism: Hansenula a
H.anomala DSM 70130, Hansenula
H.minuta DSM 70274, Hansenula Sa
H. subpelliculosa IFO 0808, C
H.wickerhamii DSM
70280, H.wingei DSM
10281 etc. (13) Microorganisms of the genus Issatchenkia: Isatche
Nkia Skullata Barity Skullata (I.scutu
lata var. scutulata) IFO 10070, etc. (14) Microorganisms of the genus Klebsiella: Klebsiella
-K. pneumoniae IFO 12059, etc. (15) Geotrichum microorganism: G. fragrans JCM 1749, etc. (16) Micrococcus microorganism: Micrococcus luteus (M. luteus) IFO 3333, Micrococcus roseus IFO 3764, etc. (17) Microorganisms of the genus Mycobacterium: M. smegmatis IFO
3153, etc. (18) Pachysolen microorganism: P. tannophilus IFO 1007, etc. (19) Paracoccus microorganism: Paracoccus denitrificans IFO 12
442, etc. (20) Microorganisms of the genus Pichia: Pichia cellobiosa (Pc
ellobiosa) DSM 2147, Pichia Farinosa (Pf
arinosa) IFO 1163, P. heedi
i) IFO 10019, IFO 10020, Pichia
P.lindnerii DSM 70718, Pichia Opuntiavality Thermo Tolerance (P.opu
ntiae var.thermotolerans) IFO 10025, IF
O 10026, P. pastoris DS
M 70382, P. querquum DS
M 70386, Pichia Sargentensis
ensis) DSM 70388, Pichia trehalophia
(P.trehalophia) DSM 70391 etc. (21) Protaminobacter microorganisms:
Protaminobacter rubber (P.ruber) IAM 108
(22) Pseudomonas genus microorganism: P. acidovorans IFO 13
582, P. diminuta IF
O 12697, Pseudomonas fluorescens (Pf
luorescens) IFO 12055, IFO 3081,
Pseudomonas putida IFO 3738
(23) Saccharomyces microorganism: S. cerevisiae IAM 02
16 etc. (24) Saccharomycopsis microorganisms:
Saccharomycopsis fibrigera IF
O 0103 etc. (25) Selenotila genus microorganism: S.peltata DSM 70579 etc. (26) Serratia genus microorganism: S. marcescens IAM 1105 etc. (27) Stefanoasca Microorganisms of the genus Stephanoascus: S. ciferrii IFO 1
284, etc. (28) Microorganisms of the genus Xanthomonas: X. maltophilia IFO 12
690, X.oryzae IAM
The microorganisms (1) to (28), such as 1657, are disclosed in Japanese Patent Application Laid-Open No. 2-195897 filed by the applicant of the present invention.

(29) Microorganisms of the genus Ambrosiozyma: A. monospora I
FO 1965, Ambrosiajima Filentoma (A.
philentoma) IFO 1847, etc. (30) Bordetella (Bordetella) microorganism: Bordetella bronchiseptica IFO 1369
1 etc. (31) Fusarium microorganisms: F. oxysporum IFO 7152, F. soiani IFO 5232, etc. (32) Gibberella microorganisms: Gibberella fujikuroi (33) Glomerella microorganism: G. cingulata IAM 8050, etc. (34) Gonatobotryum microorganism: G. apiculatum IFO
9098, etc. (35) Neosartorya genus microorganisms: Neosartorya fischerii variti spinosa (N. fisc)
(36) Oospora microorganism: O. astringenes IFO 7001, etc. (37) Paecilomyces microorganism: P. variotii IFO 4855 (38) Preussia microorganism: P. terricola IFO 7893, etc. (39) Spetoria microorganism: S. glycines IFO 5294, etc. (40) Talaromyces Genus microorganisms: T. flavus var. Var. Flavus var.
flavus) IFO 7231 (41) Microorganisms of the genus Westerdykella: W. multispora IF
O5813 and the like The microorganisms (29) to (41) are disclosed in Japanese Patent Application No. 1-325360 filed by the applicant of the present invention.

(42) Rhodococcus microorganism: R. rhodochrous DS
M43273, Rhodococcus erythropolis (R. eryt
hropolis) DSM 43274, R. roseus JCM 2158, etc. (43) Gordona sp.
(G. sputi) JCM 3228 and the like The microorganisms of (42) and (43) are disclosed in Japanese Patent Application No. 2-276100 filed by the applicant of the present invention.

(44) A microorganism belonging to the genus Eremascus:
Elemascus Fertilis IFO
(69) Microorganisms of the genus Syringospora: S. claussenii IFO 075
9 etc. (46) Microorganisms of the genus Sporopachydermia: S. lactat
(47) Microorganisms of the genus Zygoascus (Z. hellenicus) IFO 1575, etc. (48) Microorganisms of the genus Zygozyma: Z. oligophaga IFO 10360, etc. (44) ) To (48) are disclosed in Japanese Patent Application No. 2-24185 filed by the applicant of the present invention.

[0022]

Any of these microorganisms can be used as long as they have the above-mentioned ability, such as a wild strain, a mutant strain, or a recombinant strain derived by a genetic technique such as cell fusion or genetic engineering.

The microorganisms with IFO numbers are:
List of Cultures, published by the Fermentation Research Institute (IFO)
Eighth Edition, Volume 1, (1988);
Available from the FO. Microorganisms with an ATCC number can be obtained from the American Type Culture Center. Microorganisms with JCM numbers can be obtained from RIKEN. Microorganisms with AHU numbers are Hokkaido University, microorganisms with DSM numbers are Deutsche Sammlung von Mikroorganismen, I
The microorganism with the AM number can be obtained from the University of Tokyo, and the microorganism with the HUT number can be obtained from Hiroshima University.

In the method of the present invention, 1,3,3
-Reacting the microorganism or a processed product thereof on a mixture of enantiomers of butanediol. In this reaction, if a trace amount of zinc is present, the ability of the microorganism to selectively and asymmetrically assimilate can be enhanced. Therefore, zinc compounds include zinc oxide, zinc sulfide, zinc fluoride, zinc carbonate, and zinc phosphate. ,
Although hardly soluble compounds such as zinc silicate and zinc cyanide can be used, water-soluble zinc compounds are usually used. Examples of the water-soluble zinc compound include zinc halides such as zinc sulfate, zinc nitrate, and zinc chloride excluding fluoride, and zinc acetate. These zinc compounds can be used alone or in combination of two or more.

The amount of the zinc compound to be used can be selected within a range that does not inhibit the asymmetric assimilation ability of the microorganism or its processed product. The amount of the zinc compound used is about 1 to 50 ppm. When the content of the zinc compound is too small, the residual amount of the optically active substance does not improve so much, and when it is too large , the assimilation ability of the microorganism or the processed product may be reduced.

[0027] The microorganism used in the present invention may be cultured for use in a medium for the reaction. The medium is not particularly limited as long as the microorganism can grow. As the carbon source of the medium,
Any of the above microorganisms can be used, and specific examples thereof include, for example, sugars such as glucose, fructose, sucrose, dextrin, and starch; alcohols such as sorbitol, ethanol, and glycerol; fumaric acid, citric acid, Organic acids such as acetic acid and propionic acid and salts thereof; hydrocarbons such as paraffin; mixtures thereof and the like can be used. As the nitrogen source, for example, ammonium salts of inorganic acids such as ammonium chloride, ammonium sulfate and ammonium phosphate; ammonium salts of organic acids such as ammonium fumarate and ammonium citrate; meat extract, yeast extract, malt extract, peptone, corn Inorganic or organic nitrogen-containing compounds such as steep liquor, casein hydrolyzate, and urea; mixtures thereof can be used. To the medium, nutrients such as inorganic salts, trace metal salts, vitamins and the like used for normal culture may be appropriately added. If necessary, the medium may contain a factor that promotes the growth of microorganisms, a buffer substance that is effective in maintaining the pH of the medium, and a factor that increases the ability to produce the target compound of the present invention, for example, 1,3-
Butanediol and the like may be added.

Cultivation of microorganisms is carried out under conditions suitable for growth, for example, when the pH of the medium is 3.0 to 9.5, preferably 4 to 8,
The reaction can be performed at a temperature of 20 to 45 ° C, preferably 25 to 37 ° C. Cultivation of the microorganism can be performed under anaerobic or aerobic conditions. The culture time is, for example, 5 to 12
It is 0 hour, preferably about 12 to 72 hours.

The asymmetric assimilation reaction includes, for example, (1) a method of adding an enantiomer mixture of 1,3-butanediol to a medium containing a zinc compound and culturing a microorganism, (2)
A method in which a zinc compound and an enantiomer mixture of 1,3-butanediol are added to a culture solution to cause a reaction, (3) the cells separated from the culture solution by centrifugation or the like, as they are or after washing, are treated with a buffer solution, water And a method of adding a zinc compound and an enantiomeric mixture of 1,3-butanediol to a suspension containing the cells and reacting the mixture. At the time of the reaction, if a carbon source such as glucose or sucrose is added as an energy source, the residual efficiency of the target compound may increase.

Further, the cells may be used as they are as live cells, and treated cells, for example, crushed cells, acetone treatment,
A processed product subjected to a process such as freeze-drying may be used.
These cells or treated cells can be used after being immobilized by a conventional method such as a polyacrylamide gel method, a sulfur-containing polysaccharide gel method (such as a carrageenan gel method), an alginate gel method, and an agar gel method. . Furthermore, an enzyme obtained from a processed bacterial cell can also be used. The enzyme can be obtained by appropriately combining and purifying conventional methods.

The enantiomer mixture of 1,3-butanediol may be used as it is, or may be a solution containing a solvent,
It may be used as a suspension or dispersion. As the solvent, water and an organic solvent that does not adversely affect the reaction can be used. In the suspension or dispersion, a surfactant or the like can be used as necessary. The enantiomeric mixture of 1,3-butanediol may be present in the reaction system at once from the beginning of the reaction, or may be added separately to the reaction system.

The amount of cells can be appropriately selected within a range that does not decrease the optical purity and assimilation rate of the target compound. The substrate 1,
The use concentration of the enantiomer mixture of 3-butanediol is not particularly limited, but is, for example, about 0.1 to 10% by weight, and preferably about 1 to 10% by weight.

The reaction conditions can be selected within a range that does not impair the production of the target compound. The pH of the reaction system is, for example, pH 3 to
The pH is about 10, preferably about 5 to 9, and the reaction temperature is, for example, about 10 to 60C, preferably about 20 to 40C. The reaction can be performed under stirring or standing for about 1 to 120 hours.

The enantiomer mixture of 1,3-butanediol is treated with a microorganism or a treated product thereof, and the S-form or R-form is asymmetrically assimilated to obtain the R-form of optically active 1,3-butanediol or The S-form selectively and efficiently remains. When the reaction time becomes longer, the residual amount of 1,3-butanediol decreases, and the optically active 1,3
-Butanediol is obtained.

The optically active 1,3-butanediol remaining by the reaction can be recovered by conventional separation and purification means.
For example, directly or after separating cells from the reaction solution, membrane separation, extraction with an organic solvent, column chromatography,
The optically active 1,3-butanediol can be easily obtained by subjecting it to ordinary purification methods such as concentration under reduced pressure and distillation. The optical purity of the optically active 1,3-butanediol can be measured, for example, by high performance liquid chromatography (HPLC) using an optical isomer separation column.

[0036]

According to the production method of the present invention, the enantiomer mixture of 1,3-butanediol can be easily and efficiently utilized selectively by the action of a microorganism or a processed product thereof, and the optical purity is high. The production of optically active 1,3-butanediol increases.

[0037]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to only these Examples.

In the examples, the optical purity was measured by acetylating the optically active 1,3-butanediol obtained by the reaction with acetyl chloride by a conventional method, and then performing high-performance liquid chromatography using an optical resolution column. [Column: Chiral Cell O, manufactured by Daicel Chemical Industries, Ltd.
D, solvent: n-hexane / 2-propanol = 19 /
5, wavelength: 220 nm, flow rate: 0.5 ml / min]. Under the above measurement conditions, the retention time of the S-form of 1,3-butanediol was 15 minutes, and the retention time of the R-form was 1
9.3 minutes.

The rate at which the ability of the microorganism to leave the optically active 1,3-butanediol increased was determined by the following equation.

R = OP 1 / OP 0 [where, r is the increasing ratio, OP 0 is the optical purity (% ee) of a cell cultured in a medium containing no zinc compound and reacted for 24 hours, and OP 1 is zinc The optical purity (% ee) when the cells were reacted for 24 hours using cells cultured in a medium containing the compound is shown.] Examples 1 to 4 Using distilled water, glucose 2%, yeast extract 0.3%,
A medium is prepared by adding a predetermined amount of zinc sulfate (heptahydrate) to a medium consisting of 0.3% malt extract and 0.5% polypeptone, and dispensed 100 ml at a time into a 500 ml Sakaguchi flask at 121 ° C. for 15 minutes. Sterilized. The following test cells were inoculated into the medium and cultured with shaking at 30 ° C. for 24 hours.

Example 1 Geotricum Candidam (G
EOtrichumcandidum) JCM7395 Example 2: Roderomyces elongisporus (Loddero
myces elongisporus) IFO 1676 Example 3: Kluyverom
yces lactis) IFO 1267 Example 4: Candida utilis I
Next, 25 g of the culture solution, 0.75 g of racemic 1,3-butanediol, and 0.1 g of calcium carbonate were mixed, and the mixture was shaken and reciprocated at 30 ° C. for 24 hours in a 500 ml Sakaguchi flask to react. After completion of the reaction, the bacteria were removed by centrifugation, and the obtained supernatant was saturated with sodium chloride.
Extracted with 50 ml of ethyl acetate. The extract was dehydrated with anhydrous sodium sulfate and desolvated under reduced pressure to obtain a syrup. The syrup was acetylated with acetyl chloride, dissolved in hexane, and the optical purity was measured by high performance liquid chromatography. As a control, cells were cultured in a medium to which zinc sulfate (heptahydrate) was not added, and reacted in the same manner as described above. The results are shown in the table.

[0042]

[Table 1] From the table, when a microorganism is allowed to act on an enantiomer mixture of 1,3-butanediol in the presence of a zinc compound, the selective assimilation ability of the microorganism is increased, and a large amount of optically active 1,3-butanediol having high optical purity is obtained. Is obtained.

────────────────────────────────────────────────── ─── Continued on the front page (58) Field surveyed (Int. Cl. ⁷ , DB name) C12P 41/00 BIOSIS (DIALOG) CA (STN)

Claims (1)

(57) [Claims] 1. A microorganism having the ability to asymmetrically assimilate said mixture or a treated product thereof is allowed to act on an enantiomer mixture of 1,3-butanediol in the presence of 1 to 50 ppm of a zinc compound, and the mixture is left. A method for producing an optically active 1,3-butanediol for recovering an optically active 1,3-butanediol , wherein the microorganism is Geotricam.
richum) Microorganism, Lodderomyces
Microorganisms, microorganisms of the genus Candida and Kruy
Selected from microorganisms of the genus Belomyces (Kluyveromyces)
At least one optically active 1,3-butanediol
Manufacturing method .