Iterative chain elongation by a pikromycin monomodular polyketide synthase

Brian J. Beck, Courtney C. Aldrich, Robert A. Fecik, Kevin A. Reynolds, David H. Sherman

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

The unique ability of the pikromycin polyketide synthase (Pik PKS) to generate 12- and 14-membered ring macrolactones presents an opportunity to explore the fundamental processes of polyketide synthesis, specifically, the mechanistic details of the chain extension process. We have overexpressed and purified PikAIII and PikAIV and demonstrated the ability of these proteins to generate triketide lactone products using 14C-methylmalonyl-CoA as the sole substrate. Monomodular PikAIII generates TKL (1) when reacted alone, and synthesizes TKL (2) upon reaction in combination with PikAIV. Product formation remains dependent on the enzymatic decarboxylation of methylmalonyl-CoA and transfer of the acyl chain within the enzyme rather than acylation by propionyl-CoA from spontaneous decarboxylation. We propose that synthesis of TKL (1) by PikAIII involves iterative assembly of the triketide chain within a PikAIII homodimer analogous to the nonmodular type I PKS systems.

Original languageEnglish (US)
Pages (from-to)4682-4683
Number of pages2
JournalJournal of the American Chemical Society
Volume125
Issue number16
DOIs
StatePublished - Apr 23 2003

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