Identification of a Cytochrome P450 Hydroxylase Gene Involved in Rifamycin Biosynthesis by Amycolatopsis mediterranei S699

  • Lee, Sang-Kil (School of Chemical Engineering, College of Engineering, Seoul National University) ;
  • Choi, Cha-Yong (School of Chemical Engineering, College of Engineering, Seoul National University) ;
  • Ahn, Jong-Seog (Laboratory of Cellular Signaling Modulator, Korea Research Institute of Bioscience and Biotechnology) ;
  • Cho, Jae-Yong (Department of Bioindustry and Technology, Sangji University) ;
  • Park, Cheon-Seok (Department of Food Science and Technology, Kyunghee University) ;
  • Yoon, Yeo-Joon (Division of Nano Sciences and Department of Chemistry, Ewha Women's University)
  • 발행 : 2004.04.01

초록

In analyzing the region of the Amycolatopsis mediterranei S699 chromosome responsible for the biosynthesis of the ansamycin antibiotic rifamycin, we identified a gene, designated orj0, which is located immediately upstream of the rifamycin polyketide synthase (PKS). Orj0 encodes a protein, on the basis of sequence-comparative analysis, that is similar to several cytochrome P450 monooxygenases from different sources. The rifamycin producer, A. mediterranei, predominantly produces rifamycin B from its macrocyclic intermediate, proansamycin X, through dehydrogenation and hydroxylation steps. However, an A. mediterranei strain, deleted in orj0 by gene replacement, no longer produced rifamycin B. Furthermore, a versatile replicative vector in A. mediterranei was constructed and rifamycin B production was restored in a complementation experiment of orj0 using this novel vector. These consecutive results verified that the arf0 protein, which is a P450 hydroxylase, is required for the production of rifamycin B in A. mediterranei.

키워드

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