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An Atypical Arginine Dihydrolase Involved in the Biosynthesis of Cyclic Hexapeptide Longicatenamides
Author(s) -
Liu Chao,
Hashimoto Junko,
Kudo Kei,
Shinya Kazuo,
Kakeya Hideaki
Publication year - 2021
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.202100181
Subject(s) - nonribosomal peptide , biosynthesis , ornithine , biochemistry , arginine , amino acid , mutant , biology , in silico , gene , gene cluster , complementation , chemistry
The incorporation of non‐proteinogenic amino acids (NPAAs) enriches the structural diversity of nonribosomal peptides. Recently, four NPAA‐containing cyclic hexapeptides, longicatenamides A−D, were isolated using a combined‐culture strategy. Based on in silico analysis, we discovered their putative biosynthetic gene cluster ( lon ) and proposed a possible biosynthetic mechanism. Surprisingly, the lon22 gene encodes an atypical arginine dihydrolase, which can also catalyze the hydrolysis of citrulline to ornithine. Phylogenetic analysis showed that Lon22‐like proteins form a novel clade that is separated from other guanidine‐modifying enzymes. After rational design, the catalytic efficiencies of a Lon22 Y80F mutant for arginine and citrulline substrates were 2.31‐ and 4.70‐fold that of the wild‐type (WT), respectively. In addition, characterization of the Lon20‐A4 adenylation domain suggested that it can incorporate both ornithine and lysine into the final products.