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J. Microbiol. Biotechnol. 2006; 16(5): 764-770

Published online May 28, 2006

Copyright © The Korean Society for Microbiology and Biotechnology.

Cloning and Characterization of a Gene Cluster for the Production of Polyketide Macrolide Dihydrochalcomycin in Streptomyces sp. KCTC 0041BP

Jaishy, Bharat Prasad , Si Kyu Lim , Ick Dong Yoo 1, Jin Cheol Yoo 2, Jae Kyung Sohng 3 and Doo Hyun Nam 3*

College of Pharmacy, Yeungnam University, Gyongsan 712-749, Korea, 1Korea Research Institute of Biotechnology and Bioscience, Daejon 305-333, Korea, 2College of Pharmacy, Chosun University, Gwangju 501-749, Korea, 3JAE KYUNG SOHNG

Abstract

Dihydrochalcomycin (GERI-155), produced by Streptomyces sp. KCTC-0041BP isolated from Korean soil, is a 16-membered macrolide antibiotic consisting of two deoxysugar moieties at C-5 and C-20 positions of a branched lactone ring. The cloning and sequencing of a gene cluster for dihydrochalcomycin biosynthesis revealed a 63-kb nucleotide region containing 25 open reading frames (ORFs). The products of all of these 25 ORFs playa role in dihydrochalcomycin biosynthesis and self-resistance against the compounds synthesized. At the core of this cluster lies a 39.6-kb polyketide synthase (PKS) region encoding eight modules in five giant multifunctional protein-coding genes (gerSI-SV). The genes responsible for the biosynthesis of deoxysugar moieties, D-chalcose and D-mycinose, and their modification and attachment were found on either side of this PKS region. The involvement of this gene cluster in dihydrochalcomycin biosynthesis was confirmed by disruption of the dehydratase (DH) domain in module 3 of the PKS gene and by metabolite analysis.

Keywords: Macrolide antibiotic, dihydrochalcomycin, biosynthetic gene cluster, polyketide synthase, Streptomyces