Discovery and biochemical characterization of prenyltransferases in the biosynthetic pathway of hericenones from Hericium erinaceus
文献类型: 外文期刊
作者: Haiyan Han;Shuang Peng;Yuxin Yang;Chao Lin;Pengchao Wang;Chang Li;Peipei Zhao;Wenbing Gong;Chunliang Xie;Xuekui Xia;Jianzhao Qi;Chengwei Liu
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关键词: Aspergillus oryzae;Hericenones;Hericium erinaceus;Mushroom;Prenyltransferase
期刊名称: Bioorganic Chemistry
ISSN: 0045-2068
年卷期: 2025 年 164 卷
页码:
收录情况: SCIE(2025版)
摘要: Hericenones, neurotrophic meroterpenoids from the medicinal mushroom Hericium erinaceus, exhibit remarkable nerve growth factor-enhancing properties with therapeutic potential for neurodegenerative disorders. Biosynthesis of these compounds requires prenyltransferase (PT)-mediated geranylation of orsellinic acid (OA, 1), though the fungal enzymes catalyzing this pivotal step remain uncharacterised. Through comprehensive genome mining of H. erinaceus, we identified eight putative UbiA-type prenyltransferases (HePT1–8). Heterologous expression in Aspergillus oryzae coupled with substrate-feeding assays revealed HePT8 as a geranyltransferase capable of 1 geranylation, producing cannabigerorcinic acid (2) - the committed precursor of hericenones. Notably, HePT7 demonstrated divergent specificity for dimethylallyl transfer to 4-hydroxybenzoate. Systematic mutagenesis uncovered critical catalytic residues (H40/D96/D100/D211/D218/Y158) coordinating Mg2+-diphosphate interactions and substrate positioning in HePT8. This work not only elucidates the foundational step in hericenone biosynthesis but significantly expands the catalytic repertoire of fungal PTs through the discovery of multifunctional enzymes with substrate plasticity. Our findings provide essential tools for bioengineering novel meroterpenoids and illuminate evolutionary convergence in fungal secondary metabolism.
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