Expanding the toolbox of enzymatic reactions accessible to organic chemists is one of the major goals in biocatalysis. Here we describe the development of an acyltransferase variant from Mycobacterium smegmatis in which a strategic Ser/Cys exchange in the catalytic triad dramatically expanded its synthetic capability to yield a biocatalyst able to efficiently catalyse the forma- tion of thioesters and tertiary amides in water. Preparative scale (250 mM) biotransformations were performed starting from different thiols and secondary amines with excellent yields and reactions times, using vinyl esters as acylating agents. The high substrate-to-catalyst ratio and the cofactor independence make this process a sustainable and cost-effective procedure that was successfully applied to the synthesis of acetyl coenzyme A as well as structurally simpler analogues. Computational stud- ies provided insights into the enzymatic selectivity and substrate recognition.
A strategic Ser/Cys exchange in the catalytic triad unlocks an acyltransferase-mediated synthesis of thioesters and tertiary amides / M.L. Contente, D. Roura Padrosa, F.E. Molinari, F. Paradisi. - In: NATURE CATALYSIS. - ISSN 2520-1158. - 3:12(2020 Dec), pp. 1020-1026.
|Titolo:||A strategic Ser/Cys exchange in the catalytic triad unlocks an acyltransferase-mediated synthesis of thioesters and tertiary amides|
CONTENTE, MARTINA LETIZIA (Primo) [Membro del Collaboration Group]
MOLINARI, FRANCESCO ENZO (Penultimo) [Membro del Collaboration Group] (Corresponding)
|Settore Scientifico Disciplinare:||Settore CHIM/11 - Chimica e Biotecnologia delle Fermentazioni|
Settore CHIM/06 - Chimica Organica
Settore CHIM/10 - Chimica degli Alimenti
|Data di pubblicazione:||dic-2020|
|Data ahead of print / Data di stampa:||30-nov-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/s41929-020-00539-0|
|Appare nelle tipologie:||01 - Articolo su periodico|