Chapter 9: Phenylpropanoid Natural Product Biosynthesis

Phenylpropane-based metabolites comprise a large repertoire of plant-based secondary metabolites. Unlike the alkaloids, these are a nitrogen-free collection of molecules, even though they arise from the nine-carbon framework of l-phenylalanine. In the very first committed step, phenylalanine is enzymatically deaminated to cinnamate and then processed to para-coumaryl-CoA. Flux continues down two distinct pathways. One involves a set of hydroxylations and O-methylations prior to radical-based dimerizations of those monolignols to lignans, such as pinoresinol and congeners. Those dimeric lignans can be polymerized into lignin as the structure-bearing complex phenylpropanoid macromolecular meshwork in woody plants. Alternatively, pinoresinol can be vectored to a host of phytoalexins, including podophyllotoxin in mayapple, the precursor to the semisynthetic anticancer drug etoposide. A second fate for the early para-coumaryl thioester metabolites is by a two-electron coupling mode, rather than the above one-electron routes. Plant type III polyketide synthases use carbanion chemistry to build chalcones, then flavones and isoflavone downstream metabolites, many with antioxidant properties.