Aromatization of natural products by a specialized detoxification enzyme.

Huang JQ#

Huang JQ(#)(1), Fang X(#)(2), Tian X(1), Chen P(1), Lin JL(1)(3), Guo XX(1), Li JX(1), Fan Z(1), Song WM(1), Chen FY(1), Ahati R(1), Wang LJ(1), Zhao Q(4), Martin C(4)(5), Chen XY(6)(7)(8).
Author information:
(1)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.
(2)State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
(3)School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
(4)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.
(5)John Innes Centre, Norwich, UK.
(6)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. [Email]
(7)School of Life Science and Technology, ShanghaiTech University, Shanghai, China. [Email]
(8)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. [Email]
(#)Contributed equally

https://dx.doi.org/10.1038/s41589-019-0446-8

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.