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

Liddle, Emma, Scott, Alan, Han, Li-Chen, Ivison, David, Simpson, Thomas J., Willis, Christine L. and Cox, Russell J. 2017. In vitro kinetic study of the squalestatin tetraketide synthase dehydratase reveals the stereochemical course of a fungal highly reducing polyketide synthase. Chemical Communications 53 (10) , pp. 1727-1730. 10.1039/C6CC10172K

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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).

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Chemistry
Publisher:	Royal Society of Chemistry
ISSN:	1359-7345
Date of First Compliant Deposit:	30 May 2019
Date of Acceptance:	13 January 2017
Last Modified:	07 Nov 2023 03:04
URI:	https://orca.cardiff.ac.uk/id/eprint/122972

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