Kyowa Hakko Kogyo Co., Ltd.

Shigeru Chiba

Akio Ozaki

Katsuhiko Ando

Hideo Mori

Takeshi Shibasaki

Keiko Ochiai

Yoichi Uosaki

Kenji Shibata

Motoo Yamasaki

Yoshinori Yamashita

Keiichi Yano

Kazuo Yamaguchi

Isao Kawamoto

Eiji Tsukuda

Yuzuru Matsuda

Toshiyuki Suzawa

Shigeto Kitamura

Mayumi Yoshida

Takeo Tanaka

Tatsuhiro Ogawa

Yoshikazu Morishita

Chieko Bando

Mika Makino

Toshihide Ikemura

Hirofumi Nakano

Shiro Akinaga

Tadashi Ashizawa

Tamio Mizukami

Ryuichiro Nakai

Youichi Uosaki

Shigeo Katsumata

Harumi Ogawa

Shingo Kakita

Noboru Fujii

Ritsuko Katahira

Toshiaki Iwasaki

Yukari Tsuji

The present invention is directed to a process for producing trans-4-hydroxy-L-proline, which is useful as a raw material for medicines or as an additive to foods. In the process, L-proline is converted into trans-4-hydroxy-L-proline in the presence of an enzyme source which is derived from a microorganism belonging to the genusorand which catalyzes the hydroxylation of L-proline into trans-4-hydroxy-L-proline, a divalent iron ion and 2-ketoglutaric acid, in an aqueous medium, and the produced trans-4-hydroxy-L-proline is collected from the aqueous medium. In addition, the present invention is directed to a process for producing trans-4-hydroxy-L-proline, wherein the L-proline biosynthesis activity of the host cell of the transformant is reinforced.

Process for producing trans-4-hydroxy-L-proline

An isolated gene encodes for a L-proline-3-hydroxylase having the amino acid sequence of SEQ ID NOS: 1, 2, 15, 16 and 17, or for a protein having enzymatic activity to hydroxylate the 3-position of L-proline and to act on free L-proline in the presence of 2-ketoglutaric acid and divalent iron ions to produce cis-3-hydroxy-L-proline. The gene is inserted into a vector and the resulting recombinant DNA is used to create a transformant. L-proline-3-hydroxylase is produced by culturing the transformant in a medium.

Process for producing cis-3-hydroxy-L-proline

Endothelin-antagonizing peptide

Provided is an industrially applicable process for producing trans-4-hydroxy-L-proline, which is useful as a raw material for medicines or as an additive to foods. In the process, L-proline is converted into trans-4-hydroxy-L-proline in the presence of an enzyme source which is derived from a microorganism belonging to the genus Dactylosporangium, Amycolatopsis or Streptomyces and which catalyzes the hydroxylation of L-proline into trans-4-hydroxy-L-proline, a divalent iron ion and 2-ketoglutaric acid, in an aqueous medium, and the produced trans-4-hydroxy-L-proline is collected from the aqueous medium. Also provided is a novel enzyme L-proline-4-hydroxylase which is useful for the process, a gene of L-proline-4-hydroxylase which is useful for the process, a transformant containing the gene, and a process for producing L-proline-4-hydroxylase using the transformant. In addition, provided is a process for producing L-proline-4-hydroxylase using the transformant which contains the gene and has a reinforced proline biosynthesis activity.

An industrially applicable process for producing cis-3-hydroxy-L-proline, which is useful as a raw material for medicines or as an additive to foods. In the process, L-proline is converted into cis-3-hydroxy-L-proline in the presence of an enzyme source which is derived from a microorganism belonging to the genus Streptomyces or Bacillus and which catalyzes hydroxylation of L-proline into cis-3-hydroxy-L-proline, a divalent iron ion and 2-ketoglutaric acid, in an aqueous medium, and the produced cis-3-hydroxy-L-proline is collected from the aqueous medium. A novel enzyme L-proline-3-hydroxylase, a gene of L-proline-3-hydroxylase which is useful for the process, a transformant containing the gene, and a process for producing L-proline-3-hydroxylase using the transformant.

Process for producing CIS-3-hydroxy-L-proline

An industrially applicable process for producing trans-4-hydroxy-L-proline, which is useful as a raw material for medicines or as an additive to foods. In the process, L-proline is converted into trans-4-hydroxy-L-proline in the presence of an enzyme source which is derived from a microorganism belonging to the genus Dactylosporangium, Amycolatopsis or Streptomyces and which catalyzes the hydroxylation of L-proline into trans-4-hydroxy-L-proline, a divalent iron ion and 2-ketoglutaric acid, in an aqueous medium, and the produced trans-4-hydroxy-L-proline is collected from the aqueous medium. Also provided is a novel enzyme L-proline-4-hydroxylase which is useful for the process, a gene of L-proline-4-hydroxylase which is useful for the process, a transformant containing the gene, and a process for producing L-proline-4-hydroxylase using the transformant. In addition, provided is a process for producing L-proline-4-hydroxylase using the transformant which contains the gene and has a reinforced proline biosynthesis activity.

The invention relates to biologically pure cultures of Streptomyces sp. RE-701 (FERM BP-3624) and Streptomyces sp. RE-629 (FERM BP-4126) that produce endothelin antagonistic peptides.

Strains of streptomyces producing endothelin antagonistic peptides

An industrially applicable process for producing cis-3-hydroxy-L-proline, which is useful as a raw material for medicines or as an additive to foods. In the process, L-proline is converted into cis-3-hydroxy-L-proline in the presence of an enzyme source which is derived from a microorganism belonging to the genus Streptomyces or Bacillus and which catalyzes hydroxylation of L-proline into cis-3-hydroxy-L-proline, a divalent iron ion and 2-ketoglutaric acid, in an aqueous medium, and the produced cis-3-hydroxy-L-proline is collected from the aqueous medium. A novel enzyme L-proline-3-hydroxylase, a gene of L-proline-3-hydroxylase which is useful for the process, a transformant containing the gene, and a process for producing L-proline-3-hydroxylase using the transformant, is also provided.

Process for producing Cis-3-hydroxy-L-proline

The present invention relates to chrolactomycin compound represented by the following formula (I): ##STR1## or pharmaceutically acceptable salts thereof having antibacterial and antitumor activities.

Chrolactomycin compound

Isolated and purified L-proline-4-hydroxylase which catalyzes hydroxylation of L-proline at the 4-position of L-proline in the presence of 2-ketoglutaric acid and a divalent iron ion to produce trans-4-hydroxy-L-proline. The L-proline-4-hydroxylase may be isolated from a microorganism selected from the group consisting of Dactylosporanlium sp. RHI deposited with the National Institute of Bioscience and Human-Technology Agency of Industrial Science and Technology, Japan, under the designation PERM BP-4400 and Amycolatopsis sp. RH2 deposited as FERM BP-4581.

Compound UCH9

Peptides represented by the following formula (I): ##STR1## wherein A represents Asn or Asp; B represents His or Lys; and E represents Ala or Ser;

A compound represented by formula (I): ##STR1## or a pharmaceutically acceptable salt thereof is provided, which has an excellent antitumor activity.

Compound UCE6

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Kawasaki, Japan

Shigeru Chiba