Expanding the Substrate Scope of Acyltransferase LovD9 for the Biosynthesis of Statin Analogues

This study identifies new acyl donors for manufacturing statin analogues through the acylation of monacolin J acid by the laboratory evolved acyltransferase LovD9. Vinyl and p‐nitrophenyl esters have emerged as alternate substrates for LovD9‐catalyzed acylation. While vinyl esters can reach product...

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Published in:Chemistry : a European journal 2023-07, Vol.29 (42), p.e202300911-n/a
Main Authors: García‐Marquina, Guillermo, Núñez‐Franco, Reyes, Grajales‐Hernández, Daniel, Jiménez‐Osés, Gonzalo, López‐Gallego, Fernando
Format: Article
Language:English
Subjects:
Acylation
Acyltransferase
biocatalysis
Biosynthesis
Chemistry
Esters
LovD9
Quantum mechanics
Reaction mechanisms
statins
substrate scope
Substrates
Vinyl esters
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Summary:This study identifies new acyl donors for manufacturing statin analogues through the acylation of monacolin J acid by the laboratory evolved acyltransferase LovD9. Vinyl and p‐nitrophenyl esters have emerged as alternate substrates for LovD9‐catalyzed acylation. While vinyl esters can reach product yields as high as the ones obtained by α‐dimethyl butyryl‐S‐methyl‐3‐mercaptopropionate (DMB‐SMMP), the thioester for which LovD9 was evolved, p‐nitrophenyl esters display a reactivity even higher than DMB‐SMMP for the first acylation step yet the acylation product yield is lower. The reaction mechanisms were elucidated through quantum mechanics (QM) calculations. This study unveils the substrate promiscuity of acyltransferase LovD9, which turns to be very efficient by accepting vinyl and p‐nitrophenyl derivatives as acyl donors for the obtaining of statin analogues.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.202300911