Liu Xiang, Li Rui-Qi, Zeng Qing-Xin, Li Yong-Quan, Chen Xin-Ai
School of Medicine and the Children's Hospital, Zhejiang University, Hangzhou 310058, China.
Institute of Pharmaceutical Biotechnology, Zhejiang University, Hangzhou 310058, China.
Microorganisms. 2023 Oct 17;11(10):2578. doi: 10.3390/microorganisms11102578.
Asperpyridone A represents an unusual class of pyridone alkaloids with demonstrated potential for hypoglycemic activity, primarily by promoting glucose consumption in HepG2 cells. Trichodin A, initially isolated from the marine fungus Trichoderma sp. strain MF106, exhibits notable antibiotic activities against . Despite their pharmacological significance, the regulatory mechanisms governing their biosynthesis have remained elusive. In this investigation, we initiated the activation of a latent gene cluster, denoted as "", through the overexpression of the ZnCys transcription factor TopC in . The activation of the cluster led to the biosynthesis of asperpyridone A, pyridoxatin, and trichodin A. Our study also elucidated that the regulator TopC exerts precise control over the biosynthesis of asperpyridone A and trichodin A through the detection of protein-nucleic acid interactions. Moreover, by complementing these findings with gene deletions involving and , we proposed a comprehensive biosynthesis pathway for asperpyridone A and trichodin A in .
曲霉吡啶酮A代表一类不同寻常的吡啶酮生物碱，已证明其具有降血糖活性的潜力，主要是通过促进HepG2细胞中的葡萄糖消耗。曲滴虫素A最初是从海洋真菌木霉属菌株MF106中分离出来的，对……表现出显著的抗菌活性。尽管它们具有药理学意义，但其生物合成的调控机制仍然难以捉摸。在本研究中，我们通过在……中过表达ZnCys转录因子TopC，启动了一个名为“”的潜在基因簇的激活。该基因簇的激活导致了曲霉吡啶酮A、吡哆素和曲滴虫素A的生物合成。我们的研究还阐明，调节因子TopC通过检测蛋白质-核酸相互作用，对曲霉吡啶酮A和曲滴虫素A的生物合成进行精确控制。此外，通过用涉及……和……的基因缺失来补充这些发现，我们提出了曲霉吡啶酮A和曲滴虫素A在……中的全面生物合成途径。
