Shionogi Company Limited

Shionogi Seiyaku Kabushiki Kaisha

Bunji Kageyama

Shigeo Yagi

Takayasu Sonoyama

Masahiro Tanimoto

Masanori Nakae

Tadashi Yoshida

Yoshimi Kawamura

Susumu Kamata

Koichi Matsumoto

Shigeru Matsutani

Toshiyuki Kamigauchi

Ryuji Sakazaki

Kobee Kobayashi

Kyozo Kawata

Hiroyoshi Tani

Tahiko Honjo

Novel antibiotic stalobacins H-1 and I-1 having physico-chemical properties as shown in Table 4 are provided, which are excellent antibiotics showing marked effects on Gram-positive bacteria.

Antibiotic stalobacins

A norbornane type ester hydrolase that enantio-selectively hydrolyzes a (.+-.) -exo-norbornane type ester represented by Formula I is provided: ##STR1## wherein R is acyl, and A and B are hydrogens, respectively, or where A and B are absent, resulting in a carbon-carbon double bond between the carbons to which A and B are attached in Formula I. The norbornane type ester hydrolase has an optimal pH of approximately 8 and a stable pH range of approximately 6 to 8.

Norbornane type ester hydrolase

A norbornane type ester hydrolase that enantio-selectively hydrolyzes a (.+-.)-exo-norbornane type ester represented by Formula I is provided: ##STR1## wherein R is acyl, and A and B are hydrogens, respectively, or where A and B are absent, resulting in a carbon-carbon double bond between the carbons to which A and B are attached in Formula I. The norbornane type ester hydrolase has an optimal pH of approximately 8 and a stable pH range of approximately 6 to 8.

Norbornane type ester hydrolase from Acetobacter pasteurianus

Method for producing optically active norborneol by ester hydrolysis

Novel antibiotic stalobacins A to I having physico-chemical properties as shown in Tables 1 to 4 are provided, which are excellent antibiotics showing marked effects on Gram-positive bacteria.

2,5-Diketo-D-gluconic acid is prepared in high yield and in high broth concentration by cultivating newly isolated microorganisms of genus Erwinia in an aqueous nutrient medium in the presence of D-glucose. The production is also possibly by simple contact of said microorganisms or their processed products therefrom, with D-glucose.

Method for preparing 2,5-diketo-D-gluconic acid

2,5-Diketo-D-gluconic acid is prepared in high yield and in high broth concentration by cultivating newly isolated microorganisms of genus Erwinia in an aqueous nutrient medium in the presence of D-glucose. The production is also possible by simple contact of said microorganisms or their processed products therefrom, with D-glucose.

Microorganisms of the genus Erwinia useful for preparing

A novel reductase is produced from a microorganism which belongs to genus Corynebacterium and is useful as a catalyst which catalizes, in the presence of NADPH, reduction of 2, 5-diketo-D-gluconic acid or its salts to 2-keto-L-gulonate or the corresponding salts thereof. It also catalizes reduction of 5-keto-D-fructose to sorbose, in the presence of NADPH.

2,5-diketo-D-gluconic acid reductase

2-Keto-L-gulonic acid is prepared directly from D-glucose by microbial conversion utilizing mixed culturing on a medium containing D-glucose, employing two kinds of microorganisms; the first, a 2,5-diketo-D-gluconic acid producing microorganism which belongs to genus Erwinia and the second, a 2-keto-L-gulonic acid producing microorganism which belongs to genus Brevibacterium or Corynebacterium. The incubation of the microorganisms in a medium containing D-glucose is used in the disclosed process. By-production of 2-keto-D-gluconic acid, the undesired isomer of the intended product is effectively prevented by employing mixed culturing because of the co-existence of both microorganisms in the medium during at least part of the entire cultivation. Namely, 2-keto-D-gluconic acid produced by the second microorganism is utilized by the first microorganism to produce 2,5-diketo-D-gluconic acid which is subsequently converted into 2-keto-L-gulonic acid by the second microorganism.

Process for preparing 2-keto-L-gulonic acid

Fermentative or enzymatic production of 2-keto-L-gulonic acid from 2,5-diketo-D-gluconic acid using living or processed mutants, being defective in metabolizing 5-keto-D-gluconic acid and incapable of producing 2-keto-D-gluconic acid. The mutant is derived from 2-keto-L-gluconic acid producing microorganisms of genus Corynebacterium. The production is carried out in the presence of nitrates and/or hydrogen donors in a preliminarily sterilized fermentation broth in which a 2,5-diketo-D-gluconic acid producing microorganism of genus Gluconobacter or Erwinia has been cultivated.

Fermentative or enzymatic production of 2-keto-L-gulonic acid

2-Keto-L-gulonic acid is prepared from 2,5-diketo-D-gluconic acid through microbial conversion. The 2-keto-L-gulonic acid producing microorganism available for this microbial conversion includes strains which belong to the genus Corynebacterium. The incubation of the microorganism in a medium containing 2,5-diketo-D-gliconic acid as well as the direct contact of any products obtained from the microbial cells with a substrate containing said 2,5-diketo-D-gluconic acid may be used in the disclosed process.

Growing community of inventors

Osaka, Japan

Bunji Kageyama