Harnessing evolutionary diversification of primary metabolism for plant synthetic biology

Plants produce numerous natural products that are essential to both plant and human physiology. Recent identification of genes and enzymes involved in their biosynthesis now provides exciting opportunities to reconstruct plant natural product pathways in heterologous systems through synthetic biology. The use of plant chassis, although still in infancy, can take advantage of plant cells' inherent capacity to synthesize and store various phytochemicals. Also, large-scale plant biomass production systems, driven by photosynthetic energy production and carbon fixation, could be harnessed for industrial-scale production of natural products. However, little is known about which plants could serve as ideal hosts and how to optimize plant primary metabolism to efficiently provide precursors for the synthesis of desirable downstream natural products or specialized (secondary) metabolites. Although primary metabolism is generally assumed to be conserved, unlike the highly-diversified specialized metabolism, primary metabolic pathways and enzymes can differ between microbes and plants and also among different plants, especially at the interface between primary and specialized metabolisms. This review highlights examples of the diversity in plant primary metabolism and discusses how we can utilize these variations in plant synthetic biology. I propose that understanding the evolutionary, biochemical, genetic, and molecular bases of primary metabolic diversity could provide rational strategies for identifying suitable plant hosts and for further optimizing primary metabolism for sizable production of natural and bio-based products in plants.