Algal Kainoid Synthases Exhibit Substrate-Dependent Hydroxylation and Cyclization Activities.
ACS Chem Biol
; 18(12): 2457-2463, 2023 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-38047879
ABSTRACT
FeII/α-ketoglutarate-dependent dioxygenases (Fe/αKG) make up a large enzyme family that functionalize C-H bonds on diverse organic substrates. Although Fe/αKG homologues catalyze an array of chemically useful reactions, hydroxylation typically predominates. Microalgal DabC uniquely forms a novel C-C bond to construct the bioactive pyrrolidine ring in domoic acid biosynthesis; however, we have identified that this kainoid synthase exclusively performs a stereospecific hydroxylation reaction on its cis substrate regioisomer. Mechanistic and kinetic analyses with native and alternative substrates identified a 20-fold rate increase in DabC radical cyclization over ß-hydroxylation with no observable 1,5-hydrogen atom transfer. Moreover, this dual activity was conserved among macroalgal RadC1 and KabC homologues and provided insight into substrate recognition and reactivity trends. Investigation of this substrate-dependent chemistry improves our understanding of kainoid synthases and their biocatalytic application.
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Base de dados:
MEDLINE
Assunto principal:
Oxigenases de Função Mista
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article