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Publication Abstract from PubMed

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 acetate elimination catalyzed by AbyA5, implicated in the formation of the key Diels-Alder substrate to give the spirocyclic system of the antibiotic abyssomicin C. Using synthetic substrate analogues, it is shown 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 show the use of a His-Ser dyad to catalyze either elimination or hydrolysis, via disparate mechanisms, under substrate control.

An Esterase-like Lyase Catalyzes Acetate Elimination in Spirotetronate/Spirotetramate Biosynthesis.,Lees NR, Han LC, Byrne MJ, Davies JA, Parnell AE, Moreland PEJ, Stach JEM, van der Kamp MW, Willis CL, Race PR Angew Chem Int Ed Engl. 2019 Feb 18;58(8):2305-2309. doi: 10.1002/anie.201812105., Epub 2019 Jan 21. PMID:30664319^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.