7FE6

AvmM Catalyzes Macrocyclization in Alchivemycin A Biosynthesis

Summary for 7FE6

• Entry DOI: 10.2210/pdb7fe6/pdb
• Related: 7FE0 7FE5
• Descriptor: AvmM, CHLORIDE ION, Alchivemycin A, ... (4 entities in total)
• Functional Keywords: avmm, macrocyclization, michael addition, biosynthetic protein-inhibitor complex, biosynthetic protein/inhibitor
• Biological source: Streptomyces sp. NBRC 109436
• Total number of polymer chains: 3
• Total formula weight: 65914.85

Authors

Zhang, B.,Ge, H.M. (deposition date: 2021-07-19, release date: 2021-09-01, Last modification date: 2023-11-29)

Primary citation

Zhu, H.J.,Zhang, B.,Wei, W.,Liu, S.H.,Xiang, L.,Zhu, J.,Jiao, R.H.,Igarashi, Y.,Bashiri, G.,Liang, Y.,Tan, R.X.,Ge, H.M.
AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesis.
Nat Commun, 13:4499-4499, 2022

PubMed Abstract: 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.

PubMed: 35922406
DOI: 10.1038/s41467-022-32088-4

Experimental method

X-RAY DIFFRACTION (2.5 Å)