Modular oxime formation by a trans-AT polyketide synthase.
Fiche publication
Date publication
mai 2023
Journal
Angewandte Chemie (International ed. in English)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRUEZ Arnaud, Pr WEISSMAN Kira
Tous les auteurs :
Minas HA, François RMM, Hemmerling F, Fraley AE, Dieterich CL, Rüdisser SH, Meoded RA, Collin S, Weissman KJ, Gruez A, Piel J
Lien Pubmed
Résumé
Modular trans-acyltransferase polyketide synthases (trans-AT PKSs) are enzymatic assembly lines that biosynthesize complex polyketide natural products. Relative to their better studied cis-AT counterparts, the trans-AT PKSs introduce remarkable chemical diversity into their polyketide products. A notable example is the lobatamide A PKS, which incorporates a methylated oxime. Here we demonstrate biochemically that this functionality is installed on-line by an unusual oxygenase-containing bimodule. Furthermore, analysis of the oxygenase crystal structure coupled with site-directed mutagenesis allows us to propose a model for catalysis, as well as identifying key protein-protein interactions that support this chemistry. Overall, our work adds oxime-forming machinery to the biomolecular toolbox available for trans-AT PKS engineering, opening the way to introducing such masked aldehyde functionalities into diverse polyketides.
Mots clés
Oximes, Polyketide synthases, biosynthesis, natural products, polyketides
Référence
Angew Chem Int Ed Engl. 2023 05 22;:e202304481