Characterization of the Mutant of Streptomyces sp. SL-387(KCTC 0102BP) Producing Aminopeptidase M Inhibitors

Aminopeptidase M 저해제를 생산하는 Streptomyces sp. SL-387 (KCTC 0102BP) 변이주의 특성

  • Chung, Myung-Chul ;
  • Chun, Hyo-Kon ;
  • Lee, Ho-Jae ;
  • Lee, Choong-Hwan ;
  • Kho, Yung-Hee
  • 정명철 (한국과학기술연구원 유전공학연구소 미생물화학연구그룹) ;
  • 전효곤 (한국과학기술연구원 유전공학연구소 미생물화학연구그룹) ;
  • 이호재 (한국과학기술연구원 유전공학연구소 미생물화학연구그룹) ;
  • 이충환 (한국과학기술연구원 유전공학연구소 미생물화학연구그룹) ;
  • 고영희 (한국과학기술연구원 유전공학연구소 미생물화학연구그룹)
  • Published : 1995.02.01

Abstract

Since the original productivity of new aminopeptidase M inhibitors MR-387A and B by Streptomyces sp. SL-387 (KCTC 0102BP) was not enough for further chemical and biological evaluation, mutation of parent strain by the treatment of N-methyl-N'-nitro-N-nitrosoguanidine was performed in order to obtain a clone with greater inhibitory activity. Mutant N-3 was selected due to a 6-fold greater productivity (40 $\mu$g/ml) than that of the wild type(6.7 $\mu$g/ml). This mutant was resistant to 3,4-dehydro-DL-proline, an antimetabolite of proline, with 25 $\mu$g/ml of minimum inhibitory concentration. Furthermore, the characteristic morphological change from spiral spore chain in wild type to straight in mutant was observed. An aminopeptidase M nhibitor different from MR-387A and B was isolated from the culture broth of the mutant. This inhibitor was composed of 2 proline, 1 valine, and an unknown amino acid which is presumably 3-amino-4-phenylbutanoic acid. IC$_{50}$ value (89.1 $\MU$g/ml) of the purified inhibitor was lower than that of other inhibitors, which may be due to the absence of 2(S)-hydroxyl group within the structure of 3-amino-4-phenyl- butanoic acid.

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