title: Biosynthesis of the Carbonylmethylene Structure Found in the Ketomemicin Class of Pseudotripeptides.
abstract: We recently discovered novel pseudotripeptides, the ketomemicins, which possess a C-terminal pseudodipeptide connected with a carbonylmethylene instead of an amide bond, through heterologous expression of gene clusters identified in actinobacteria. The carbonylmethylene structure is a stable isostere of the amide bond and its biological significance has been shown in several natural and synthetic products. Despite the biological importance of these compounds, little is known about how the carbonylmethylene structure is biosynthesized. In this work, we fully characterized the biosynthetic machinery of the pseudodipeptide. An aldolase, dehydratase, PLP-dependent glycine-C-acetyltransferase, and dehydrogenase were involved in the formation of the pseudodipeptide, with malonyl-CoA and phenylpyruvate as starter substrates.
authors.affiliation: Graduate School of Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Kawata
authors.affiliation: Graduate School of Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Naoe
authors.affiliation: Graduate School of Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ogasawara
authors.affiliation: Graduate School of Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Dairi
mesh_terms: D039903:Actinobacteria / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D005810:Multigene Family; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057786:Peptidomimetics / Q000737:chemistry / Q000378:metabolism*; D010667:Phenylpyruvic Acids / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D057786:Peptidomimetics; D010667:Phenylpyruvic Acids; D005634:Fructose-Bisphosphate Aldolase; C031606:phenylpyruvic acid
keywords: biosynthesis; enzymes; natural products; peptidomimetics; pseudopeptides