title: Genome mining of the hitachimycin biosynthetic gene cluster: involvement of a phenylalanine-2,3-aminomutase in biosynthesis.
abstract: Hitachimycin is a macrolactam antibiotic with (S)-β-phenylalanine (β-Phe) at the starter position of its polyketide skeleton. To understand the incorporation mechanism of β-Phe and the modification mechanism of the unique polyketide skeleton, the biosynthetic gene cluster for hitachimycin in Streptomyces scabrisporus was identified by genome mining. The identified gene cluster contains a putative phenylalanine-2,3-aminomutase (PAM), five polyketide synthases, four β-amino-acid-carrying enzymes, and a characteristic amidohydrolase. A hitA knockout mutant showed no hitachimycin production, but antibiotic production was restored by feeding with (S)-β-Phe. We also confirmed the enzymatic activity of the HitA PAM. The results suggest that the identified gene cluster is responsible for the biosynthesis of hitachimycin. A plausible biosynthetic pathway for hitachimycin, including a unique polyketide skeletal transformation mechanism, is proposed.
authors: Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551 (Japan).
authors: Fumitaka
authors: F
authors: Kudo
authors: Koichi
authors: K
authors: Kawamura
authors: Asuka
authors: A
authors: Uchino
authors: Akimasa
authors: A
authors: Miyanaga
authors: Mario
authors: M
authors: Numakura
authors: Ryuichi
authors: R
authors: Takayanagi
authors: Tadashi
authors: T
authors: Eguchi
mesh_terms: D016680:Genome, Bacterial / Q000235:genetics; D023281:Genomics; D019751:Intramolecular Transferases / Q000235:genetics* / Q000378:metabolism*; D005810:Multigene Family; D010649:Phenylalanine / Q000378:metabolism*; D011090:Polyenes / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism
chemical_list: D011090:Polyenes; D010649:Phenylalanine; C031780:stubomycin; D019751:Intramolecular Transferases
keywords: antibiotics; biosynthesis; genome mining; hitachimycin; macrolactam polyketide; phenylalanine-2,3-aminomutase