@inbook{4ca27487fa6a4ad6b7a034319be419d7,
title = "Chapter 8 Type I Polyketide Synthases That Require Discrete Acyltransferases",
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.",
author = "Cheng, {Yi Qiang} and Coughlin, {Jane M.} and Lim, {Si Kyu} and Ben Shen",
note = "Funding Information: This work was supported in part by National Institutes of Health grants CA106150 and CA113297.",
year = "2009",
doi = "10.1016/S0076-6879(09)04608-4",
language = "English",
isbn = "9780123745910",
series = "Methods in Enzymology",
number = "B",
pages = "165--186",
editor = "David Hopwood",
booktitle = "Complex Enzymes in Microbial Natural Product Biosynthesis, Part B",
edition = "B",
}