Recent advances in biosynthesis of bioactive compounds in traditional Chinese medicinal plants

Abstract

Plants synthesize and accumulate large amount of specialized (or secondary) metabolites also known as natural products, which provide a rich source for modern pharmacy. In China, plants have been used in traditional medicine for thousands of years. Recent development of molecular biology, genomics and functional genomics as well as high-throughput analytical chemical technologies has greatly promoted the research on medicinal plants. In this article, we review recent advances in the elucidation of biosynthesis of specialized metabolites in medicinal plants, including phenylpropanoids, terpenoids and alkaloids. These natural products may share a common upstream pathway to form a limited numbers of common precursors, but are characteristic in distinct modifications leading to highly variable structures. Although this review is focused on traditional Chinese medicine, other plants with a great medicinal interest or potential are also discussed. Understanding of their biosynthesis processes is critical for producing these highly value molecules at large scale and low cost in microbes and will benefit to not only human health but also plant resource conservation.

Keywords: Alkaloid; Biosynthesis; Medicinal plant; Phenylpropanoid; Terpenoid.

Fig. 1

(Color online) Biosynthesis of phenylpropanoids in TCM plants. a Biosynthesis of flavonoids and isopentenyl flavonoids; b formation of phenolic acids from the l-phenylalanine- and the l-tyrosine-derived pathways in Salvia miltiorrhiza, a medicinal plant of Lamiaceae. Phenylpropanoids are mainly synthesized from phenylalanine via the “general phenylpropanoid pathway”, catalyzed by phenylalanine ammonialyase (PAL), cinnamate 4-hydroxylase (C4H) and p-coumaroyl coenzyme A ligase (4CL). The product of p-coumaroyl-CoA is used for the biosynthesis of flavonoids, isopentenyl flavonoids and phenolic acids. CHS, chalcone synthase; CHI, chalcone isomerase; FNS, flavone synthase; IFS, isoflavone synthase; FPT, flavonoid prenyltransferase; TAT, tyrosine aminotransferase; HPPR, 4-hydroxyphenylpyruvate reductase; RAS, rosmarinic acid synthase; P450, cytochrome P450 monooxygenase. Dotted lines represent multiple enzymatic catalyzed steps

Fig. 2

(Color online) Biosynthesis of terpenoids in TCM plants. Terpenoids are synthesized via the cytosol MVA pathway and plastid MEP pathway. Generally, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) synthesized from the MVA pathway are converted to farnesyl diphosphate (FPP) for the biosynthesis of sesquiterpenoids and triterpenoids, whereas those derived from the MEP pathway contribute to the formation of geranyl diphosphate (GPP) and geranylgeranyl diphosphate (GGPP) for biosynthesis of monoterpenoids, diterpenoids and tetraterpenoids. HMG-CoA, 3-hydroxy-3-methylglutaryl-CoA; MEP, 2-C-methyl-D-erythritol 4-phosphate; GGPP, geranylgeranyl diphosphate; HMGR, 3-hydroxy-3-methylglutaryl-CoA reductase; DXS, 1-deoxy-D-xylulose-5-phosphate synthase; DXR, 1-deoxy-D-xylulose-5-phosphate reductoisomerase; GPPS, geranyl diphosphate synthase; GPP, geranyl diphosphate; FPPS, farnesyl diphosphate synthase; GGPPS, geranylgeranyl diphosphate synthase; TPS, terpene synthase; SS, squalene synthase; SE, squalone epoxidase; OSC, oxidosqualene cyclase. Dotted lines represent multiple enzymatic catalyzed steps