7fe6

AvmM Catalyzes Macrocyclization in Alchivemycin A Biosynthesis

spinqualitylabelsall models 7fe6, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7fe6 is a 3 chain structure with sequence from Streptomyces sp. NBRC 109436. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: CL, ZHU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A8F7LEJ5_9ACTN Publication Abstract from PubMed Macrocyclization is an important process that affords morphed scaffold in biosynthesis of bioactive natural products. Nature has adapted diverse biosynthetic strategies to form macrocycles. In this work, we report the identification and characterization of a small enzyme AvmM that can catalyze the construction of a 16-membered macrocyclic ring in the biosynthesis of alchivemycin A (1). We show through in vivo gene deletion, in vitro biochemical assay and isotope labelling experiments that AvmM catalyzes tandem dehydration and Michael-type addition to generate the core scaffold of 1. Mechanistic studies by crystallography, DFT calculations and MD simulations of AvmM reveal that the reactions are achieved with assistance from the special tenuazonic acid like moiety of substrate. Our results thus uncover an uncharacterized macrocyclization strategy in natural product biosynthesis. AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesis.,Zhu HJ, Zhang B, Wei W, Liu SH, Xiang L, Zhu J, Jiao RH, Igarashi Y, Bashiri G, Liang Y, Tan RX, Ge HM Nat Commun. 2022 Aug 3;13(1):4499. doi: 10.1038/s41467-022-32088-4. PMID:35922406 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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