Chapter 8 Type I Polyketide Synthases That Require Discrete Acyltransferases

Yi Qiang Cheng, Jane M. Coughlin, Si Kyu Lim, Ben Shen

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

36 Scopus citations

Abstract

The diverse structures of polyketide natural products are reflected by the equally diverse polyketide biosynthetic enzymes, namely polyketide synthases (PKSs). Three major classes of PKSs are known-noniterative type I PKSs, iterative type II PKSs and acyl carrier protein-independent type III PKSs, each of which consists of additional variants. One such variant is the noniterative type I PKS in which each PKS module lacks the cognate acyltransferase (AT) domain. The essential AT activity is instead provided by a discrete AT in trans. Termed "AT-less" type I PKSs, the loading of the malonate extender units by the discrete AT enzyme LnmG to each of the AT-less PKS modules of LnmI and LnmJ was confirmed experimentally for biosynthesis of the anticancer antibiotic leinamycin (LNM). The LNM PKS has since served as a model for the continuous discovery of numerous additional AT-less type I PKSs incorporating variable extender units. However, biochemical characterization of AT-less type I PKSs remains very limited, and the mechanism by which AT-less type I PKSs accommodate multiple extender units is unknown. This chapter provides the protocols used to establish and characterize the LNM PKS. Application of these methods to other AT-less type I PKSs should aid the biochemical characterization and hence possible exploitation of these unique PKSs for polyketide natural product structural diversity by combinatorial biosynthetic methods.

Original languageEnglish
Title of host publicationComplex Enzymes in Microbial Natural Product Biosynthesis, Part B
Subtitle of host publicationPolyketides, Aminocoumarins and Carbohydrates
EditorsDavid Hopwood
Pages165-186
Number of pages22
EditionB
DOIs
StatePublished - 2009

Publication series

NameMethods in Enzymology
NumberB
Volume459
ISSN (Print)0076-6879

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