Molecular Decoration and Unconventional Double Bond Migration in Irumamycin Biosynthesis DOI Creative Commons
Vera A. Alferova, Anna A. Baranova, Olga A. Belozerova

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(12), P. 1167 - 1167

Published: Dec. 3, 2024

Irumamycin (Iru) is a complex polyketide with pronounced antifungal activity produced by type I (PKS) synthase. Iru features unique hemiketal ring and an epoxide group, making its biosynthesis the structural diversity of related compounds particularly intriguing. In this study, we performed detailed analysis iru biosynthetic gene cluster (BGC) to uncover mechanisms underlying formation. We examined PKS, including domain architecture individual modules overall spatial structure uncovered discrepancies in substrate specificity iterative chain elongation. Two potential pathways for formation ring, involving either olefin shift or electrocyclization, were proposed assessed using 18O-labeling experiments reaction activation energy calculations. Based on our findings, likely formed PKS-assisted double bond migration TE domain-mediated cyclization. Furthermore, putative tailoring enzymes mediating specific identified. The revealed machinery provides insight into enzymatic processes involved production, macrocycle sculpting decoration. These mechanistic details open new avenues targeted novel macrolide analogs through synthetic biology engineering.

Language: Английский

Molecular Decoration and Unconventional Double Bond Migration in Irumamycin Biosynthesis DOI Creative Commons
Vera A. Alferova, Anna A. Baranova, Olga A. Belozerova

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(12), P. 1167 - 1167

Published: Dec. 3, 2024

Irumamycin (Iru) is a complex polyketide with pronounced antifungal activity produced by type I (PKS) synthase. Iru features unique hemiketal ring and an epoxide group, making its biosynthesis the structural diversity of related compounds particularly intriguing. In this study, we performed detailed analysis iru biosynthetic gene cluster (BGC) to uncover mechanisms underlying formation. We examined PKS, including domain architecture individual modules overall spatial structure uncovered discrepancies in substrate specificity iterative chain elongation. Two potential pathways for formation ring, involving either olefin shift or electrocyclization, were proposed assessed using 18O-labeling experiments reaction activation energy calculations. Based on our findings, likely formed PKS-assisted double bond migration TE domain-mediated cyclization. Furthermore, putative tailoring enzymes mediating specific identified. The revealed machinery provides insight into enzymatic processes involved production, macrocycle sculpting decoration. These mechanistic details open new avenues targeted novel macrolide analogs through synthetic biology engineering.

Language: Английский

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