Deciphering the Regioselective Acylation Modification in Bipentaromycin
Mengsong Chen , Guohui Shang , Xingyu Chen , Yunchang Xie , Chunhuan Li , Chunshuai Huang
Chinese Journal of Chemistry ›› 2025, Vol. 43 ›› Issue (17) : 2137 -2142.
Deciphering the Regioselective Acylation Modification in Bipentaromycin
Aromatic polyketides (APKs) are renowned for their structural diversity and potent biological activities, making them valuable resources for drug discovery in antibiotics, anticancer agents, and antiparasitic therapies. Bipentaromycins, a unique class of dimeric APKs with a cyclic head-to-tail linkage, exhibit broad-spectrum antibacterial activities. Acylation modifications in bipentaromycins C–F enhance their pharmacological properties, yet the responsible acyltransferase remains enigmatic. Herein, we present REGAIN, an innovative strategy combining restriction enzyme digestion, Gibson assembly, and in vivo Cre-lox recombination, enabling rapid and efficient cloning of biosynthetic gene clusters (BGCs). Using REGAIN, we successfully cloned a 40 kb bipentaromycin BGC (bpm). By integrating genetic experiments and computational modeling, we speculated BpmP as the acyltransferase responsible for regioselective acylation. This study establishes a robust platform for exploring novel bioactive molecules and advances the understanding of bipentaromycin biosynthesis.
Direct cloning / REGAIN / Bipentaromycin / Biosynthesis / Acyltransferase / Computational modeling / Inactivation / Active sites
2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
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