Process for the deacylation of cyclic lipopeptides
AssigneeFujisawa Pharmaceutical Co., Ltd.
InventorsSatoshi Ueda, Miho Tanaka, Masami Ezaki, Kazutoshi Sakamoto, Seiji Hashimoto, Nobutaka Oohata, Masaru Tsuboi, Michio Yamashita
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Abstract
There is provided a cyclic lipopeptide acylase which is capable of deacylating the acyl side chain of a cyclic lipopeptide compound, e.g. Substance FR901379 or its analog, of the general formula [I] with effectiveness as well a method of producing a cyclic peptide compound which comprises using the acylase.
Claims9
An isolated acylase enzyme obtained from Streptomyces anulatus No. 4811 or Streptomyces anulatus No. 8703, wherein said enzyme catalyzes deacylation of the acyl group R1 of a cyclic lipopeptide compound of the following general formula I or a salt thereof:
- wherein
- R1 is acyl;
- R2 is hydroxy or acyloxy;
- R3 is hydrogen or hydroxy;
- R4 is hydrogen or hydroxy;
- R5 is hydrogen or hydroxysulfonyloxy;
- and
- R6 is hydrogen or carbamoyl;
- to produce a cyclic peptide compound of the following general formula [II] or a salt thereof:
- wherein R2, R3, R4, R5, and R6 are as defined above;
- wherein said enzyme deacylates at an optimal pH of 8.0, at an optimal temperature of 50° C., and is activated in a concentration-dependent manner by methanol, wherein activation increases up to 10% by volume concentration of methanol, wherein the enzyme does not deacylate the compound FR901469.
An isolated enzyme obtained from Streptomyces No. 6907, comprising a large peptide and a small peptide wherein said large peptide comprises SEQ ID NO:1 and said small peptide comprises SEQ ID NO:2, wherein said enzyme catalyzes the deacylation of the lipid acyl moiety of a cyclic lipopeptide at an optimal pH of 9.0, an optimal temperature of 50° C., and is activated in a concentration-dependent manner by methanol, wherein activation increases up to 10% by volume concentration of methanol, and wherein the enzyme does not deacylate the compound FR901469.
Dependencies are inferred from the claim text.