Issue 2, 2016

Polyketide synthase and non-ribosomal peptide synthetase thioesterase selectivity: logic gate or a victim of fate?

Abstract

Covering: 1999 to 2014

Type 1, α/β hydrolase-like thioesterase (TE) domains are essential offloading enzymes, releasing covalently bound products from fatty acid, polyketide, and non-ribosomal peptide biosynthetic complexes. The release step can occur by attack of an exogenous nucleophile effecting hydrolysis or transesterification or by an intramolecular O-, N-, or C-nucleophile, effecting macrolactonization, macrolactamization or Claisen-like condensation of the product. Thus in addition to ensuring turnover of the pathway, TEs provide access to increased chemical diversity. We review the diversity, structure, and mechanism of PKS and NRPS TEs and discuss recent works that highlight the role of TEs as potential arbitrators in offloading. In particular, we examine cases where TEs act as logic gates that ask a particular question about the substrate and use this information to determine the substrate's fate. As the TE mechanism occurs via two steps, we analyze both the loading and release steps independently as logic gates. The use of logic gates provides an important perspective when evaluating the evolution of TEs within a pathway, as well as highlighting work towards the goal of predicting TE function in unknown and engineered pathways.

Graphical abstract: Polyketide synthase and non-ribosomal peptide synthetase thioesterase selectivity: logic gate or a victim of fate?

Supplementary files

Article information

Article type
Review Article
Submitted
12 Nov. 2014
First published
02 Febr. 2015

Nat. Prod. Rep., 2016,33, 183-202

Polyketide synthase and non-ribosomal peptide synthetase thioesterase selectivity: logic gate or a victim of fate?

M. E. Horsman, T. P. A. Hari and C. N. Boddy, Nat. Prod. Rep., 2016, 33, 183 DOI: 10.1039/C4NP00148F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements