Probing the mysteries of lignin biosynthesis: the crystal structure of caffeic acid/5-hydroxyferulic acid 3/5-O-methyltransferase provides new insights.

Caffeic acid/5-hydroxyferulic acid 3/5O -methyltransferase (COMT) is a small-molecule S -adenosylL -Met–dependent O -methyltransferase (OMT) that is one of the principal enzymes in the complex network of reactions that take place as part of lignin biosynthesis (Figure 1). Plants contain a wide variety of S -adenosylL -Met–dependent OMTs that act on Phe-derived substrates during the production of numerous plant “secondary” compounds in addition to lignin, such as anthocyanin flower pigments, isoflavonoid antimicrobial compounds, phytoestrogens and allelochemicals, coumarin defense compounds, and chalcone nodulation factors. Some OMTs exhibit a high degree of substrate specificity. For example, chalcone OMT (ChOMT) from alfalfa methylates the 2 -hydroxyl of 4,2 ,4 -trihydroxychalcone to produce 4,4 -dihydroxy-2 -methoxychalcone, which is an inducer of Rhizobia nodulation genes, and isoflavone OMT (IOMT) converts a putative isoflavone substrate to formononetin, a potent phytoestrogen that also is a precursor of medicarpin, the principal antifungal phytoalexin of alfalfa. In contrast to ChOMT and IOMT, COMT exhibits broader substrate specificity. It is a bifunctional enzyme that methylates substrates at the 5-hydroxy and 3-hydroxy positions on the aromatic ring and acts (with varying affinity) on free acid, aldehyde, and alcohol 3-hydroxy and 3,5-dihydroxy phenylpropanoid substrates. The broad specificity of COMT is one of the main reasons that monolignol biosynthesis is viewed as a highly complex network or grid, and definitive in vivo pathways have yet to be determined. In this issue of The Plant Cell , Zubieta et al. (pages 1265–1277) present an analysis of the crystal structure of COMT from alfalfa that Figure 1. COMT Is One of the Key Enzymes Involved in Monolignol Biosynthesis in Angiosperms.