Genome mining of the hitachimycin biosynthetic gene cluster: involvement of a phenylalanine-2,3-aminomutase in biosynthesis

Chembiochem : a European Journal of Chemical Biology
Fumitaka KudoTadashi Eguchi

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.

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Jun 14, 2014·Natural Product Reports·Fumitaka KudoTadashi Eguchi

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Citations

Jul 22, 2015·Chembiochem : a European Journal of Chemical Biology·Yiguang ZhuChangsheng Zhang
Oct 10, 2015·Genome Announcements·Hisayuki KomakiYasuhiro Igarashi
Sep 14, 2016·Current Opinion in Chemical Biology·Akimasa MiyanagaTadashi Eguchi
Apr 11, 2017·Chemical Reviews·Adrian T Keatinge-Clay
May 13, 2017·Chemical Reviews·Fabio ParmeggianiNicholas J Turner
Jun 30, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jing WangLinzhuan Wu
Apr 6, 2019·Acta Crystallographica. Section F, Structural Biology Communications·Jolanta CieślakTadashi Eguchi
Jun 6, 2020·The Journal of Antibiotics·Akimasa MiyanagaTadashi Eguchi
Apr 30, 2017·Genome Announcements·Melissa Vazquez-HernandezSergio Sánchez
Feb 20, 2020·Journal of Natural Products·Yern-Hyerk ShinDong-Chan Oh

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