State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
J Agric Food Chem. 2024 Aug 28;72(34):19061-19070. doi: 10.1021/acs.jafc.4c05177. Epub 2024 Aug 15.
Sorbicillinoids are a class of fungal polyketides with diverse structures and distinguished bioactivities. Although remarkable progress has been achieved in their chemistry and biosynthesis, the efflux of sorbicillinoids is poorly understood. Here, we found MFS transporter AcsorT was responsible for the biosynthesis of sorbicillinoids in . Combinatorial knockout and subcellular location demonstrated that the plasma membrane-associated AcsorT was responsible for the transportation of sorbicillinol and subsequent formation of oxosorbicillinol and acresorbicillinol C via the berberine bridge enzyme-like oxidase AcsorD in the periplasm. Homology modeling and site-directed mutation revealed that Tyr and Arg were the key residues of AcsorT, which was further explained by molecular dynamics simulation. Based on our study, it was suggested that AcsorT modulates sorbicillinoid production by coordinating its biosynthesis and export, and a transport model of sorbicillinoids was proposed in .
索比菌素类是一类具有多样结构和独特生物活性的真菌聚酮化合物。尽管在其化学和生物合成方面已经取得了显著的进展，但对其外排机制仍知之甚少。在这里，我们发现 MFS 转运蛋白 AcsorT 负责 中索比菌素类的生物合成。组合敲除和亚细胞定位表明，质膜相关的 AcsorT 负责将 sorbicillinol 运输到周质中，并通过类似于黄莲碱桥酶的氧化酶 AcsorD 将其进一步转化为 oxosorbicillinol 和 acresorbicillinol C。同源建模和定点突变表明 Tyr 和 Arg 是 AcsorT 的关键残基，分子动力学模拟进一步解释了这一点。基于我们的研究，提出 AcsorT 通过协调其生物合成和外排来调节索比菌素类的产生，并且在 中提出了一个索比菌素类的运输模型。
