Analysis of the biosynthetic pathway and the regulatory mechanism of secondary metabolites in Streptomyces

2009 Fiscal Year Final Research Report

• Project/Area Number: 20780083
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Bioproduction chemistry/Bioorganic chemistry
• Research Institution: Hiroshima University
• Principal Investigator: ARAKAWA Kenji Hiroshima University, 大学院・先端物質科学研究科, 助教 (80346527)
• Project Period (FY): 2008 – 2009
• Keywords: 生合成 / 抗生物質 / ポリケチド / 制御遺伝子 / 転写活性化因子 / 糖転移酵素

Research Abstract

We analyzed the function of the secondary metabolites genes located on the linear plasmid pSLA2-L. In LC biosynthesis, the C-18 amine group in an acyclic compound is oxidized by LkcE to form the iminium intermediate, which then receives the nucleophilic attack from C-2 enolate to form the 17-membered macrocyclic LC. We also determined the order of post-PKS modification in LM biosynthesis. The extensive transcriptional analysis has revealed that the γ-butyrolactone signaling cascade goes from srrX through srrA to srrY, leading to LC and LM production.

Research Products

• [Journal Article] Regulation of lankamycin biosynthesis in Streptomyces rochei by two SARP genes, srrY and srrZ (2010)
  • Author(s): T. Suzuki, S. Mochizuki, S. Yamamoto, K. Arakawa, H. Kinashi
  • Journal Title: Biosci. Biotechnol. Biochem 74(in press)
  • Peer Reviewed
• [Journal Article] The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics (2010)
  • Author(s): T. Auerbach, I. Mermershtain, C. Davidovich, A. Bashan, M. Belousoff, I. Wekselman, E. Zimmerman, L. Xiong, D. Klepacki, K. Arakawa, H. Kinashi, A. Mankin, A. Yonath
  • Journal Title: Proc. Natl. Acad. Sci. USA 107 Pages: 1983-1988
  • Peer Reviewed
• [Journal Article] Extensive mutational analysis of modular-iterative mixed polyketide biosynthesis of lankacidin in Streptomyces rochei (2009)
  • Author(s): S. Tatsuno, K. Arakawa, H. Kinashi
  • Journal Title: Biosci. Biotechnol. Biochem 73 Pages: 2712-2719
  • Peer Reviewed
• [Journal Article] Gene disruption analysis of two glycosylation steps in lankamycin biosynthesis in Streptomyces rochei (2008)
  • Author(s): K. Arakawa, T. Suzuki, H. Kinashi
  • Journal Title: Actinomycetol 22 Pages: 35-41
  • Peer Reviewed
• [Journal Article] γ-Butyrolactone-dependent expression of the SARP gene srrY plays a central role in the regulatory cascade leading to lankacidin and lankamycin production in Streptomyces rochei (2008)
  • Author(s): S. Yamamoto, Y. He, K. Arakawa, H. Kinashi
  • Journal Title: J. Bacteriol 190 Pages: 1308-1316
  • Peer Reviewed
• [Presentation] 放線菌線状プラスミドにコードされた生合成遺伝子群の機能解析 (2009)
  • Author(s): 荒川賢治
  • Organizer: 2009年度日本放線菌学会大会
  • Place of Presentation: 秋田県秋田市
  • Year and Date: 2009-07-16
• [Presentation] Regulation of lankacidin and lankamycin biosynthesis in Streptomyces rochei (2008)
  • Author(s): 荒川賢治
  • Organizer: Japan-UK Workshop on Genomics of Antibiotic-producing Actinomycetes: Implications and Applications
  • Place of Presentation: 日本大学・東京
  • Year and Date: 2008-10-31
• [Presentation] A modular-iterative mixed polyketide synthases and oxidative macrocyclization in the biosynthesis of the 17-membered antibiotic lankacidin (2008)
  • Author(s): 荒川賢治
  • Organizer: 7th-Japan-US seminar
  • Place of Presentation: 米国San Diego
  • Year and Date: 2008-05-31
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/mbiotech/hosenkin_lab/hosen_lab.html