生物
基因
基因簇
蘑菇
基因组
小桶
生物信息学
计算生物学
作者
Jin-Tao Cheng,Han-Min Wang,Jia-Hui Yu,Chen-Fan Sun,Fei Cao,Xin-Hang Jiang,Xin-Ai Chen,Qing-Wei Zhao,Li-She Gan,Rongrong Xie,Shi-Lei Wang,Jia Li,Yi Zang,Xu-Ming Mao
标识
DOI:10.1021/acs.jafc.1c03639
摘要
Liver fibrosis has accounted for liver diseases and overall mortality, but no relevant drug has been developed. Filamentous fungi are important resources of natural products for pharmaceutical development. Calcarisporium arbuscula is a mushroom endophytic fungus, which primarily produces aurovertins. Here, in an aurovertin null-production mutant, one silent gene cluster (mca17) was activated by overexpression of a pathway-specific zinc finger transcriptional regulator, and a tetramic acid-type compound (1, MCA17-1) was identified. Along with detailed structural characterization, its biosynthesis was proposed to be produced from the core PKS-NRPS hybrid enzyme. Moreover, 1 suppressed the activation of LX-2 upon transforming growth factor-β (TGF-β) challenge and had stronger bioactivity than the positive control obeticholic acid (OCA) against liver fibrosis. Our work suggested that this engineered fungus could be a producer of 1 for promising pharmaceutical development, and alternatively, it would be developed as a mushroom ingredient in dietary therapy to prevent liver fibrosis.
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