PDF(Pubmed)
Abstract：
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 Staphylococcus epidermidis. 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 \"top\", through the overexpression of the Zn2Cys6 transcription factor TopC in Tolypocladium ophioglossoides. The activation of the top 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 topA and topH, we proposed a comprehensive biosynthesis pathway for asperpyridone A and trichodin A in T. ophioglossoides.
摘要：
吡啶酮A代表一类不寻常的吡啶酮生物碱，具有潜在的低血糖活性，主要通过促进HepG2细胞中的葡萄糖消耗。毛滴虫A,最初从海洋真菌木霉属中分离出来。菌株MF106对表皮葡萄球菌表现出明显的抗生素活性。尽管它们具有药理学意义，控制其生物合成的调控机制仍然难以捉摸。在这次调查中,我们启动了潜在基因簇的激活，表示为“顶部”，通过Zn2Cys6转录因子TopC在苦参中的过表达。顶部簇的激活导致了asperpyidoneA的生物合成，吡哆昔他汀,我们的研究还阐明了调节因子TopC通过检测蛋白质-核酸相互作用对吡啶酮A和trichodinA的生物合成具有精确的控制作用。此外，通过涉及topA和topH的基因缺失来补充这些发现，我们提出了一个全面的生物合成途径。
