Biosynthesis of the allylmalonyl-CoA extender unit for the FK506 polyketide synthase proceeds through a dedicated polyketide synthase and facilitates the …

…, MO Lee, KS Lee, SJ Kim, D Kim, BC Park…

Index: Mo, Sangjoon; Kim, Dong Hwan; Lee, Jong Hyun; Park, Je Won; Basnet, Devi B.; Ban, Yeon Hee; Yoo, Young Ji; Chen, Shu-Wei; Park, Sung Ryeol; Choi, Eun Ae; Kim, Eunji; Jin, Ying-Yu; Lee, Sung-Kwon; Park, Ju Yeol; Liu, Yuan; Lee, Mi Ok; Lee, Keum Soon; Kim, Sang Jun; Kim, Dooil; Park, Byoung Chul; Lee, Sang-Gi; Kwon, Ho Jeong; Suh, Joo-Won; Moore, Bradley S.; Lim, Si-Kyu; Yoon, Yeo Joon Journal of the American Chemical Society, 2011 , vol. 133, # 4 p. 976 - 985

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Citation Number: 101

Abstract

The allyl moiety of the immunosuppressive agent FK506 is structurally unique among polyketides and critical for its potent biological activity. Here, we detail the biosynthetic pathway to allylmalonyl-coenzyme A (CoA), from which the FK506 allyl group is derived, based on a comprehensive chemical, biochemical, and genetic interrogation of three FK506 gene clusters. A discrete polyketide synthase (PKS) with noncanonical domain ...