De-regulation of tyrosine biosynthesis facilitated evolutionary expansion of diverse plant natural products
|演題||De-regulation of tyrosine biosynthesis facilitated evolutionary expansion of diverse plant natural products|
|講演者||Dr. Hiroshi Maeda, Department of Botany, University of Wisconsin-Madison|
Plants synthesize numerous natural products, which play crucial roles in plant adaptation and human health. In contrast to well-documented diversification of specialized metabolic enzymes, little is known about the evolution of primary metabolic enzymes that provide precursors to the production of various specialized metabolites.
The plant order Caryophyllales (e.g. beet, quinoa, cactus) uniquely produces red/yellow betalains pigments that are derived from the aromatic amino acid L-tyrosine (Tyr) and replaced the otherwise ubiquitous phenylalanine (Phe)-derived anthocyanins. In most plants, Tyr production is strongly feedback regulated by Tyr at arogenate dehydrogenase (TyrA); however, we found that TyrA enzymes in Caryophyllales recently duplicated into two isoforms, one of which (TyrAα) exhibits relaxed sensitivity to Tyr inhibition. Interestingly, the de-regulated TyrAα emerged before the evolution of the betalain biosynthetic pathway. Metabolite profiling further revealed that other Tyr-derived compounds, such as dopamine and epinephrine, also accumulate in TyrAα-containing Caryophyllales species. Phylogeny-guided structure function analysis of TyrA enzymes from over hundreds of Caryophyllales transcriptome data identified key mutations responsible for the Tyr insensitivity of TyrAα enzymes. Finally, heterologous expression of beet TyrAα in Nicotiana benthamiana and Arabidopsis thaliana resulted in hyper-accumulation of Tyr and decreased synthesis of Phe.
These results together demonstrate that de-regulation of Tyr biosynthesis redirected carbon flux from Phe to Tyr biosynthesis, which likely pre-conditioned for the evolutionary expansion of diverse specialized metabolites derived from Tyr. Our finding also highlights the significance of upstream primary metabolic regulation for the diversification of specialized metabolism in plants, and also provides novel engineering tools to improve the production of Tyr and Tyr-derived natural products, such as morphine alkaloid and vitamin E.
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