Yuhui Sun, Xiufen Zhou, Hui Dong, Guoquan Tu, Min Wang, Bofei Wang, and Zixin Deng*
Chemistry & Biology 2003, 10(5):431-441
Epub Date: 14 June 2003
DOI: 10.1007/s00203-003-0564-1
The PKS genes for biosynthesis of the polyether nanchangmycin are
organized to encode two sets of proteins (six and seven ORFs,
respectively), but are separated by independent ORFs that encode an
epimerase, epoxidase, and epoxide hydrolase, and, notably, an
independent ACP. One of the PKS modules lacks a corresponding ACP. We
propose that the process of oxidative cyclization to form the polyether
structure occurs when the polyketide chain is still anchored on the
independent ACP before release. 4-O-methyl-L-rhodinose
biosynthesis and its transglycosylation involve four putative genes, and
regulation of nanchangmycin biosynthesis seems to involve activation as
well as repression. In-frame deletion of a KR6 domain generated the
nanchangmycin aglycone with loss of 4-O-methyl-L-rhodinose and
antibacterial activity, in agreement with the assignments of the PKS
domains catalyzing specific biosynthetic steps.
Yuhui Sun, Xiufen Zhou, Guoquan Tu, and Zixin Deng*
Archives of Microbiology 2003, 180(2):101-107
First published:16 May 2003
DOI: 10.1016/S1074-5521(03)00092-9
A cluster encoding genes for the biosynthesis of meilingmycin, a macrolide antibiotic structurally similar to avermectin and milbemycin α11,was identified among seven uncharacterized polyketide synthase gene clusters isolated from Streptomyces nanchangensis NS3226 by hybridization with PCR products using primers derived from the sequences of aveE, aveF and a thioesterase domain of the avermectin biosynthetic gene cluster. Introduction of a 24.1-kb deletion by targeted gene replacement resulted in a loss of meilingmycin production, confirming that the gene cluster encodes biosynthesis of this important anthelminthic antibiotic compound. A sequenced 8.6-kb fragment had aveC and aveE homologues (meiC and meiE) linked together, as in the avermectin gene cluster, but the arrangementof aveF (meiF) and the thioesterase homologues differed. The results should pave the way to producing nove linsecticidal compounds by generating hybrids between the two pathways.