6lta

Publication Abstract from PubMed

Nonribosomal peptide synthetases (NRPSs) are attractive targets for bioengineering to generate useful peptides . F moA3 is a single modular NRPS composed of heterocyclization (Cy), adenylation (A), and peptidyl carrier protein (PCP) domains. It use s alpha - methyl- l -serine to synthesize a 4-methyloxazoline ring, probably with another Cy domain in the preceding module FmoA2. Here, we determined the head-to-tail homodimeric structures of FmoA3 by X-ray crystallography ( apo -form, with adenylyl-imidodiphosphate and alpha -methyl- l -seryl-AMP) and cryogenic electron microscopy single particle analysis, and performed site-directed mutagenesis experiments. The data revealed that alpha -methyl- l -serine can be accommodated in the active site because of the extra space around Ala688. The Cy domains of FmoA2 and FmoA3 catalyze peptide bond formation and heterocyclization, respectively. FmoA3's Cy domain seems to lose its donor PCP binding activit y. The collective data support a proposed catalytic cycle of FmoA3.

Structural and functional analyses of the tridomain-nonribosomal peptide synthetase FmoA3 for 4-methyloxazoline ring formation.,Katsuyama Y, Sone K, Harada A, Kawai S, Urano N, Adachi N, Moriya T, Kawasaki M, Shin-Ya K, Senda T, Ohnishi Y Angew Chem Int Ed Engl. 2021 Mar 29. doi: 10.1002/anie.202102760. PMID:33783097^[1]

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