Identification of a gene cluster of polyether antibiotic lasalocid from Streptomyces lasaliensis

Bioscience, Biotechnology, and Biochemistry
Akira MigitaHideaki Oikawa

Abstract

Elucidation of enzymatic polyether formation is a long-standing controversial issue in organic chemistry. To address this intriguing issue, identifying the actual substrate for epoxidation and sequential cyclization is essential. We selected the representative polyether ionophore, lasalocid, which has been proposed to undergo no modification at the late stage of biosynthesis. Cloning and a sequence analysis revealed seven polyketide synthase (PKS) genes, epoxidase and epoxide hydrolase genes for sequential ether formation, and several putative genes for supplying ethylmalonyl-CoA. Based on bioinformatic data, we propose the lasalocid biosynthetic pathway which involves characteristic aromatic ring formation and sequential cyclic ether formation. The finding of a thioesterase domain at the C-terminal of the seventh PKS indicates that intriguing oxidative cascade cyclization would occur after cleavage of the polyketide intermediate from PKS. Based on this observation, we have recently reported the enzymatic transformation of a bisepoxide intermediate to lasalocid with the recombinant epoxide hydrolase, Lsd19.

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Citations

Feb 4, 2010·Journal of the American Chemical Society·Christopher T Walsh, Michael A Fischbach
Mar 23, 2011·Applied and Environmental Microbiology·Hao WangYing Huang
Oct 25, 2011·Chemical Reviews·Christopher J ThibodeauxHung-wen Liu
Jun 26, 2013·Current Opinion in Chemical Biology·Atsushi MinamiHideaki Oikawa
Apr 11, 2017·Chemical Reviews·Adrian T Keatinge-Clay
Dec 7, 2013·Angewandte Chemie·Petra PöplauJörn Piel
Dec 14, 2011·Applied and Environmental Microbiology·Chunyan JiangLinquan Bai
Mar 17, 2012·Nature·David E Cane
Oct 26, 2011·Angewandte Chemie·Manuela TosinPeter F Leadlay
Jun 17, 2014·Natural Product Reports·Ryan M Van WagonerJeffrey L C Wright
Dec 20, 2019·Journal of Industrial Microbiology & Biotechnology·Ran LiuTiangang Liu
Apr 13, 2017·Applied Microbiology and Biotechnology·Xiaojie ZhangLinquan Bai
Dec 24, 2014·Journal of the American Chemical Society·Fong T WongChu-Young Kim
Apr 18, 2012·Journal of the American Chemical Society·Atsushi MinamiHideaki Oikawa

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