title: Genome Mining of Amino Group Carrier Protein-Mediated Machinery: Discovery and Biosynthetic Characterization of a Natural Product with Unique Hydrazone Unit.
abstract: We recently revealed that a Streptomyces strain possesses the gene encoding amino group carrier protein (AmCP). AmCP is involved in the biosynthesis of a previously unidentified nonproteinogenic amino acid, (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH), which is a core compound for the synthesis of the dipeptide-containing novel natural product vazabitide A. We used polymerase chain reaction (PCR) screening to investigate the diversity of the biosynthetic machinery that uses AmCP; the results revealed that genes encoding AmCP are widely distributed among actinomycetes. The heterologous expression of the AmCP-containing gene cluster from Streptomyces sp. SoC090715LN-17 led to the discovery of s56-p1, a novel natural product. The structure of s56-p1 was determined by spectroscopic analysis; the results revealed that s56-p1 has a putative DADH-derived molecule as the core and also possesses a unique hydrazone unit that is rarely observed in natural products. Our results pave the way for investigations of unexploited AmCP-mediated biosynthesis routes among actinomycetes and of the biosynthetic mechanism of the unique hydrazone unit.
authors.affiliation: Biotechnology Research Center, The University of Tokyo , Tokyo 133-8657, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Biotechnology Research Center, The University of Tokyo , Tokyo 133-8657, Japan.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Hasebe
authors.affiliation: Genome Research Center, NODAI Research Institute, Tokyo University of Agriculture , Tokyo 156-8502, Japan.
authors.forename: Yuh
authors.initials: Y
authors.lastname: Shiwa
authors.affiliation: Genome Research Center, NODAI Research Institute, Tokyo University of Agriculture , Tokyo 156-8502, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kanesaki
authors.affiliation: Biotechnology Research Center, The University of Tokyo , Tokyo 133-8657, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Tomita
authors.affiliation: Genome Research Center, NODAI Research Institute, Tokyo University of Agriculture , Tokyo 156-8502, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshikawa
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST) , Tokyo 135-0064 Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-Ya
authors.affiliation: Biotechnology Research Center, The University of Tokyo , Tokyo 133-8657, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kuzuyama
authors.affiliation: Biotechnology Research Center, The University of Tokyo , Tokyo 133-8657, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishiyama
mesh_terms: D039903:Actinobacteria / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D053898:Biosynthetic Pathways; D016680:Genome, Bacterial; D006835:Hydrazones / Q000737:chemistry / Q000378:metabolism*; D005810:Multigene Family; D013302:Streptomyces / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001688:Biological Products; D006835:Hydrazones