Genome Mining of the Hitachimycin Biosynthetic Gene Cluster: Involvement of a Phenylalanine‐2,3‐aminomutase in Biosynthesis |
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| Authors: | Prof Dr Fumitaka Kudo Koichi Kawamura Asuka Uchino Dr Akimasa Miyanaga Mario Numakura Ryuichi Takayanagi Prof Dr Tadashi Eguchi |
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| Affiliation: | 1. Department of Chemistry, Tokyo Institute of Technology, 2‐12‐1 O‐okayama, Meguro‐ku, Tokyo 152‐8551 (Japan);2. Department of Chemistry and Materials Science, Tokyo Institute of Technology, 2‐12‐1 O‐okayama, Meguro‐ku, Tokyo 152‐8551 (Japan) |
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| 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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| Keywords: | antibiotics biosynthesis genome mining hitachimycin macrolactam polyketide phenylalanine‐2 3‐aminomutase |
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