Issue 10, 2017

In vitro kinetic study of the squalestatin tetraketide synthase dehydratase reveals the stereochemical course of a fungal highly reducing polyketide synthase

Abstract

Six potential diketide substrates for the squalestatin tetraketide synthase (SQTKS) dehydratase (DH) domain were synthesised as N-acetyl cysteamine thiolesters (SNAC) and tested in kinetic assays as substrates with an isolated DH domain. 3R-3-hydroxybutyryl SNAC 3R-16 was turned over by the enzyme, but its enantiomer was not. Of the four 2-methyl substrates only 2R,3R-2-methyl-3-hydroxybutyryl SNAC 2R,3R-8 was a substrate. Combined with stereochemical information from the isolated SQTKS enoyl reductase (ER) domain, our results provide a near complete stereochemical description of the first cycle of beta-modification reactions of a fungal highly reducing polyketide synthase (HR-PKS). The results emphasise the close relationship between fungal HR-PKS and vertebrate fatty acid synthases (vFAS).

Graphical abstract: In vitro kinetic study of the squalestatin tetraketide synthase dehydratase reveals the stereochemical course of a fungal highly reducing polyketide synthase

Supplementary files

Article information

Article type
Communication
Submitted
22 Dec 2016
Accepted
13 Jan 2017
First published
13 Jan 2017

Chem. Commun., 2017,53, 1727-1730

In vitro kinetic study of the squalestatin tetraketide synthase dehydratase reveals the stereochemical course of a fungal highly reducing polyketide synthase

E. Liddle, A. Scott, L. Han, D. Ivison, T. J. Simpson, C. L. Willis and R. J. Cox, Chem. Commun., 2017, 53, 1727 DOI: 10.1039/C6CC10172K

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