Shionogi Company Limited

Shigeo Yagi

Bunji Kageyama

Takayasu Sonoyama

Masahiro Tanimoto

Tadashi Yoshida

Yoshimi Kawamura

Susumu Kamata

Koichi Matsumoto

Shigeru Matsutani

Toshiyuki Kamigauchi

Ryuji Sakazaki

Masanori Nakae

Akio Takimoto

Kobee Kobayashi

Hiroyoshi Tani

Kenji Mitsushima

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

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.

A cephalosporin acetylhydrolase gene, a recombinant DNA molecule prepared by introducing said gene into a vector used in an E. coli host-vector system, E. coli cells transformed with said recombinant DNA molecule, a protein having the amino acid sequence encoded by said gene, an enzyme which is a multimer of said protein, and a process for preparing said protein or enzyme are provided, said cephalosporin acetylhydrolase being an enzyme useful for converting cephalosporins such as cephalosporin C and 7-ACA into deacetylated ones such as deacetylcephalosporin C and deacetyl 7-ACA which are useful as an intermediate for preparing a variety of derivatized cephalosporin antibiotics.

Cephalosporin acetylhydrolase gene from Bacillus subtilis

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

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.

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Osaka, Japan

Shigeo Yagi