Evolutionary tuning of a biosynthetic gene cluster drives furanocoumarin accumulation and diversification

Xiaoxu Han; Miaoxian Guo; Peng Yang; Donghua Hu; Yuanxia Chen; Yujie Jia; Hongcui Pei; Jiantao Tan; Elsayed Nishawy; Zefu Lu; Anthony Twamley; Garth Maker; Li Wang

doi:10.1038/s41467-026-74337-w

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Evolutionary tuning of a biosynthetic gene cluster drives furanocoumarin accumulation and diversification

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Evolutionary tuning of a biosynthetic gene cluster drives furanocoumarin accumulation and diversification

Xiaoxu Han, Miaoxian Guo, Peng Yang, Donghua Hu, Yuanxia Chen, Yujie Jia, Hongcui Pei, Jiantao Tan, Elsayed Nishawy, Zefu Lu, …

Nature communications, In Press

2026

DOI: https://doi.org/10.1038/s41467-026-74337-w

PMID: 42304001

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Abstract

Deciphering evolutionary drivers of biosynthetic pathways could enhance bioactive compound production. In Angelica, interspecific variation in furanocoumarins (FCs) accumulation reflects divergent pathway evolution. Here, we conduct comparative genomics between high-FC Angelica sensu stricto (s.s.) and low-FC Angelica sensu lato (s.l.) species. We reveal an FC biosynthetic gene cluster (BGC) comprising core enzymes (p-coumaroyl-CoA 2'-hydroxylases (C2'Hs), prenyltransferases (PTs)) and peripheral O-methyltransferases (OMTs). The ancestral Angelica s.l. clade retains an FC BGC configuration with OMTs on separate chromosomes and PTs performing only C-prenylation. In contrast, Angelica s.s. evolves an FC BGC, where core enzymes and OMTs co-localise on the same chromosome, with C2'H copy number expansion correlating with elevated expression and PTs enabling both C- and O-prenylation, collectively enhancing FC production and structural diversity. These findings elucidate how BGC architecture, gene copy number and functional innovation collectively drive phytochemical innovation, providing a blueprint for engineering medicinal FC biosynthesis.

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Title: Evolutionary tuning of a biosynthetic gene cluster drives furanocoumarin accumulation and diversification
Authors/Creators: Xiaoxu Han - Agricultural Genomics Institute at Shenzhen
Miaoxian Guo - University College Dublin
Peng Yang - Hunan University of Traditional Chinese Medicine
Donghua Hu - Agricultural Genomics Institute at Shenzhen
Yuanxia Chen - Agricultural Genomics Institute at Shenzhen
Yujie Jia - University College Dublin
Hongcui Pei - Chinese Academy of Agricultural Sciences
Jiantao Tan - Rice Research Institute
Elsayed Nishawy - National Water Research Center
Zefu Lu - Chinese Academy of Agricultural Sciences
Anthony Twamley - University College Dublin
Garth Maker - Murdoch University
Li Wang - Agricultural Genomics Institute at Shenzhen
Publication Details: Nature communications, In Press
Publisher: Nature Research
Grant note: 32400192 / National Natural Science Foundation of China (National Science Foundation of China) 32470245 / National Natural Science Foundation of China (National Science Foundation of China) 32570274 / National Natural Science Foundation of China (National Science Foundation of China) 32300223 / National Natural Science Foundation of China (National Science Foundation of China)
Identifiers: 991005896087007891
Murdoch Affiliation: School of Medical, Molecular and Forensic Sciences; Centre for Computational and Systems Medicine
Language: English
Resource Type: Journal article

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