7qan

Publication Abstract from PubMed

Abyssomicin C and its atropisomer are potent inhibitors of bacterial folate metabolism. They possess complex polycyclic structures, and their biosynthesis has been shown to involve several unusual enzymatic transformations. Using a combination of synthesis and in vitro assays we reveal that AbyV, a cytochrome P450 enzyme from the aby gene cluster, catalyses a key late-stage epoxidation required for the installation of the characteristic ether-bridged-core of abyssomicin C. The X-ray crystal structure of AbyV has been determined, which in combination with molecular dynamics simulations provides a structural framework for our functional data. This work demonstrates the power of combining selective carbon-13 labelling with NMR spectroscopy as a sensitive tool to interrogate enzyme-catalysed reactions in vitro with no need for purification.

The Role of Cytochrome P450 AbyV in the Final Stages of Abyssomicin C Biosynthesis.,Devine AJ, Parnell AE, Back CR, Lees NR, Johns ST, Zulkepli AZ, Barringer R, Zorn K, Stach JEM, Crump MP, Hayes MA, van der Kamp MW, Race PR, Willis C Angew Chem Int Ed Engl. 2022 Oct 31. doi: 10.1002/anie.202213053. PMID:36314667^[1]

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