Microbiology and Biotechnology Letters (한국미생물·생명공학회지)

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Improvement of Cyclosporin A Hydroxylation in Sebekia benihana by Conjugational Transfer of Streptomyces coelicolor SCO4967, a Secondary Metabolite Regulatory Gene

Sebekia benihana에서 Streptomyces coelicolor SCO4967 유전자 도입을 통한 하이드록실 사이클로스포린 A의 생전환

  • Kim, Hyun-Bum (Department of Biological Engineering, Inha University) ;
  • Lee, Mi-Jin (Department of Biological Engineering, Inha University) ;
  • Han, Kyu-Boem (CHA BIO & DIOSTECH Bio Pharmaceutical Research Institute) ;
  • Kim, Eung-Soo (Department of Biological Engineering, Inha University)
  • 김현범 (인하대학교 생물공학과) ;
  • 이미진 (인하대학교 생물공학과) ;
  • 한규범 (차바이오&디오스텍 바이오 의약연구소) ;
  • 김응수 (인하대학교 생물공학과)
  • Received : 2010.08.03
  • Accepted : 2010.10.07
  • Published : 2010.12.28
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Abstract

Actinomycetes are Gram-positive soil bacteria and one of the most important industrial microorganisms due to superior biosynthetic capabilities of many valuable secondary metabolites as well as production of various valuable bioconversion enzymes. Among them are cytochrome P450 hydroxylase (CYP), which are hemoproteins encoded by a super family of genes, are universally distributed in most of the organisms from all biological kingdoms. Actinomycetes are a rich source of soluble CYP enzymes, which play critical roles in the bioactivation and detoxification of a wide variety of metabolite biosynthesis and xenobiotic transformation. Cyclosporin A (CyA), one of the most commonly-prescribed immunosuppressive drugs, was previously reported to be hydroxylated at the position of 4th N-methyl leucine by a rare actinomycetes called Sebekia benihana, leading to display different biological activity spectrum such as loss of immunosuppressive activities yet retaining hair growth-stimulating side effect. In order to improve this regio-selective CyA hydroxylation in S. benihana, previously-identified several secondary metabolite up-regulatory genes from Streptomyces coelicolor and S. avermitilis were heterologously overexpressed in S. benihana using an $ermE^*$ promoter-containing Streptomyces integrative expression vector. Among tested, SCO4967 encoding a conserved hypothetical protein significantly stimulated region-specific CyA hydroxylation in S. benihana, implying that some common regulatory systems functioning in both biosynthesis and bioconversion of secondary metabolite might be present in different actinomycetes species.

Keywords

References

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