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An Esterase‐like Lyase Catalyzes Acetate Elimination in Spirotetronate/Spirotetramate Biosynthesis

Lookup NU author(s): Dr Polly Moreland, Dr James StachORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Wiley, 2019.

For re-use rights please refer to the publisher's terms and conditions.


Spirotetronate and spirotetramate natural products include a multitude of compounds with potent antimicrobial and antitumor activities. Their biosynthesis incorporates many unusual biocatalytic steps, including regio- and stereo-specific modifications, cyclizations promoted by Diels-Alderases, and acetylation-elimination reactions. Here we focus on the intriguing acetate elimination catalyzed by AbyA5, implicated in formation of the key Diels-Alder substrate to give the spirocyclic system of the antibiotic abyssomicin C. Using synthetic substrate analogues we show that AbyA5 catalyzes stereospecific acetate elimination, establishing the (R)-tetronate acetate as a biosynthetic intermediate. The X-ray crystal structure of AbyA5, the first of an acetate eliminating enzyme, reveals a deviant acetyl esterase fold. Molecular dynamics simulations and enzyme assays demonstrate use of a His-Ser dyad to catalyze either elimination or hydrolysis, via disparate mechanisms, under substrate control.

Publication metadata

Author(s): Lees NR, Han LC, Byrne MJ, Davies JA, Parnell AE, Moreland PEJ, Stach JEM, van der Kamp MW, Willis CL, Race PR

Publication type: Article

Publication status: Published

Journal: Angewandte Chemie International Edition

Year: 2019

Volume: 58

Issue: 8

Pages: 2305-2309

Print publication date: 11/02/2019

Online publication date: 21/01/2019

Acceptance date: 20/12/2018

Date deposited: 07/01/2019

ISSN (print): 0044-8249

ISSN (electronic): 1521-3757

Publisher: Wiley


DOI: 10.1002/anie.201812105


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