Leinamycin Biosynthesis Revealing Unprecedented Architectural Complexity for a Hybrid Polyketide Synthase and Nonribosomal Peptide Synthetase

Gong Li Tang, Yiqiang Cheng, Ben Shen

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

A 135,638 bp DNA region that encompasses the leinamycin (LNM) biosynthetic gene cluster was sequenced from Streptomyces atroolivaceus S-140. The boundaries of the lnm cluster were defined by systematic inactivation of open reading frames within the sequenced region. The lnm cluster spans 61.3 kb of DNA and consists of 27 genes encoding nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), hybrid NRPS-PKS, resistance, regulatory, and tailoring enzymes, as well as proteins of unknown function. A model for LNM biosynthesis is proposed, central to which is the LNM hybrid NRPS-PKS megasynthetase consisting of discrete (LnmQ and LnmP) and modular (LnmI) NRPS, acyltransferase-less PKS (LnmG, LnmI, and LnmJ), and PKS modules with unusual domain organization. These studies unveil an unprecedented architectural complexity for the LNM hybrid NRPS-PKS megasynthetase and set the stage to investigate the molecular basis for LNM biosynthesis.

Original languageEnglish
Pages (from-to)33-45
Number of pages13
JournalChemistry and Biology
Volume11
Issue number1
DOIs
StatePublished - 1 Jan 2004

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