Aromatization of natural products by a specialized detoxification enzyme

ABSTRACT In plants, lineage-specific metabolites can be created by activities derived from the catalytic promiscuity of ancestral proteins, although examples of recruiting detoxification

systems to biosynthetic pathways are scarce. The ubiquitous glyoxalase (GLX) system scavenges the cytotoxic methylglyoxal, in which GLXI isomerizes the α-hydroxy carbonyl in the

methylglyoxal–glutathione adduct for subsequent hydrolysis. We show that GLXIs across kingdoms are more promiscuous than recognized previously and can act as aromatases without cofactors. In

cotton, a specialized GLXI variant, SPG, has lost its GSH-binding sites and organelle-targeting signal, and evolved to aromatize cyclic sesquiterpenes bearing α-hydroxyketones to synthesize

defense compounds in the cytosol. Notably, SPG is able to transform acetylated deoxynivalenol, the prevalent mycotoxin contaminating cereals and foods. We propose that detoxification

enzymes are a valuable source of new catalytic functions and SPG, a standalone enzyme catalyzing complex reactions, has potential for toxin degradation, crop engineering and design of novel

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BEING VIEWED BY OTHERS INCORPORATION OF NITROGEN IN ANTINUTRITIONAL _SOLANUM_ ALKALOID BIOSYNTHESIS Article Open access 13 September 2024 THE BIOSYNTHETIC PATHWAY OF POTATO SOLANIDANES

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Article 28 May 2025 DATA AVAILABILITY The authors declare that all relevant data supporting the findings of this study are available within the paper and its Supplementary Information. The

FLNC reads and HiSeq transcriptomic reads generated in this study have been deposited in the NCBI SRA database under accession number PRJNA493958. Moreover, datasets generated and/or

analyzed during the current study are available from the corresponding author upon reasonable request. CODE AVAILABILITY All code used in this study is available from the corresponding

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ACKNOWLEDGEMENTS We thank W. Hu, S. Bu and Y. Liu for help with GC–MS, NMR and Q-TOF analyses and X. Hao, B. Xu, B. Yang, C. Shi, Y. Hu, Y. Li, L. Chen and K. Zhai for their kind and

generous help. We also thank D. Nelson for naming the CYP protein. The research was supported by grants from the National Natural Science Foundation of China (Nos. 31788103, 31690092 to

X.-Y.C. and No. 31700263 to J.X.L.), the Ministry of Agriculture of China (grant No. 2016ZX08010002-005 to L.J.W.), the Ministry of Science and Technology of China (grant No. 2016YFD0100500

to L.J.W.) and the Chinese Academy of Sciences (grant Nos. XDB11030000, QYZDY-SSW-SMC026 and 153D31KYSB20160074 to X.-Y.C.). AUTHOR INFORMATION Author notes * These authors contributed

equally: Jin-Quan Huang, Xin Fang. AUTHORS AND AFFILIATIONS * State Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of

Plant Physiology and Ecology, University of CAS, Chinese Academy of Sciences, Shanghai, China Jin-Quan Huang, Xiu Tian, Ping Chen, Jia-Ling Lin, Xiao-Xiang Guo, Jian-Xu Li, Zhen Fan, 

Wei-Meng Song, Fang-Yan Chen, Ruzha Ahati, Ling-Jian Wang & Xiao-Ya Chen * State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese

Academy of Sciences, Kunming, China Xin Fang * School of Life Science and Technology, ShanghaiTech University, Shanghai, China Jia-Ling Lin & Xiao-Ya Chen * Shanghai Key Laboratory of

Plant Functional Genomics and Resources, Shanghai Chenshan Botanical Garden, Shanghai Chenshan Plant Science Research Center, Chinese Academy of Sciences, Shanghai, China Qing Zhao, Cathie

Martin & Xiao-Ya Chen * John Innes Centre, Norwich, UK Cathie Martin Authors * Jin-Quan Huang View author publications You can also search for this author inPubMed Google Scholar * Xin

Fang View author publications You can also search for this author inPubMed Google Scholar * Xiu Tian View author publications You can also search for this author inPubMed Google Scholar *

Ping Chen View author publications You can also search for this author inPubMed Google Scholar * Jia-Ling Lin View author publications You can also search for this author inPubMed Google

Scholar * Xiao-Xiang Guo View author publications You can also search for this author inPubMed Google Scholar * Jian-Xu Li View author publications You can also search for this author

inPubMed Google Scholar * Zhen Fan View author publications You can also search for this author inPubMed Google Scholar * Wei-Meng Song View author publications You can also search for this

author inPubMed Google Scholar * Fang-Yan Chen View author publications You can also search for this author inPubMed Google Scholar * Ruzha Ahati View author publications You can also search

for this author inPubMed Google Scholar * Ling-Jian Wang View author publications You can also search for this author inPubMed Google Scholar * Qing Zhao View author publications You can

also search for this author inPubMed Google Scholar * Cathie Martin View author publications You can also search for this author inPubMed Google Scholar * Xiao-Ya Chen View author

publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS J.-Q.H., X.F., X.T. and X.-Y.C. designed and managed the study. C.M., X.F., X.T., W.-M.S., Q.Z. and

L.-J.W. discussed results and provided advice. J.-Q.H. isolated genes and characterized enzymes. J.-Q.H., X.T., J.-L.L., X.-X.G., R.A. and F.-Y.C. isolated compounds and performed LC–MS and

GC–MS analyses. X.F. and Z.F. analyzed the NMR data. J.-Q.H., P.C. and Q.Z. performed bioinformatic analysis. J.-X.L. modeled the enzymes. X.-Y.C., J.-Q.H., X.F. and C.M. wrote the

manuscript with input from all authors. CORRESPONDING AUTHOR Correspondence to Xiao-Ya Chen. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL

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INFORMATION Supplementary Tables 1 and 2, Figs. 1–9 and Note. REPORTING SUMMARY RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Huang, JQ., Fang, X.,

Tian, X. _et al._ Aromatization of natural products by a specialized detoxification enzyme. _Nat Chem Biol_ 16, 250–256 (2020). https://doi.org/10.1038/s41589-019-0446-8 Download citation *

Received: 30 July 2019 * Accepted: 26 November 2019 * Published: 13 January 2020 * Issue Date: March 2020 * DOI: https://doi.org/10.1038/s41589-019-0446-8 SHARE THIS ARTICLE Anyone you share

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