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 aromatics.
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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.
All code used in this study is available from the corresponding author upon reasonable request.
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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.).
The authors declare no competing interests.
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Huang, J., Fang, X., Tian, X. et al. Aromatization of natural products by a specialized detoxification enzyme. Nat Chem Biol (2020) doi:10.1038/s41589-019-0446-8