Terpene Synthases as Metabolic Gatekeepers in the Evolution of Plant Terpenoid Chemical Diversity

Abstract

Terpenoids comprise tens of thousands of small molecule natural products that are widely distributed across all domains of life. Plants produce by far the largest array of terpenoids with various roles in development and chemical ecology. Driven by selective pressure to adapt to their specific ecological niche, individual species form only a fraction of the myriad plant terpenoids, typically representing unique metabolite blends. Terpene synthase (TPS) enzymes are the gatekeepers in generating terpenoid diversity by catalyzing complex carbocation-driven cyclization, rearrangement, and elimination reactions that enable the transformation of a few acyclic prenyl diphosphate substrates into a vast chemical library of hydrocarbon and, for a few enzymes, oxygenated terpene scaffolds. The seven currently defined clades (a-h) forming the plant TPS family evolved from ancestral triterpene synthase- and prenyl transferase–type enzymes through repeated events of gene duplication and subsequent loss, gain, or fusion of protein domains and further functional diversification. Lineage-specific expansion of these TPS clades led to variable family sizes that may range from a single TPS gene to families of more than 100 members that may further function as part of modular metabolic networks to maximize the number of possible products. Accompanying gene family expansion, the TPS family shows a profound functional plasticity, where minor active site alterations can dramatically impact product outcome, thus enabling the emergence of new functions with minimal investment in evolving new enzymes. This article reviews current knowledge on the functional diversity and molecular evolution of the plant TPS family that underlies the chemical diversity of bioactive terpenoids across the plant kingdom.

The foxtail millet (Setaria italica) terpene synthase gene family

“…(Chen et al, 2011). Downstream of this central precursor pool, the vast chemical space of species-specific terpenoids is largely determined by terpene synthases (TPSs), cytochrome P450 monooxygenases (P450s) and other modifying enzyme classes (Banerjee and Hamberger, 2018;Karunanithi and Zerbe, 2019). Most commonly, TPSs catalyze the cyclization and rearrangement of their respective prenyl pyrophosphate substrates to generate a range of mono-(C10), sesqui-(C15) and di-(C20) terpenoid scaffolds (Chen et al, 2011).…”

“…The majority of these enzymes represent class I TPSs that initiate substrate conversion through cleavage of the pyrophosphate leaving group. Uniquely, in angiosperms the formation of labdane diterpene scaffolds, which include kauranes, pimaranes, abietanes and related terpene groups, recruits pairs of class II and class I diTPSs that function sequentially to generate distinct scaffolds (Peters, 2010;Karunanithi and Zerbe, 2019). Here, the central diterpenoid precursor, geranylgeranyl pyrophosphate (GGPP), first undergoes protonation-dependent cyclization by a class II diTPS to generate bicyclic prenyl pyrophosphate intermediates of different normal (+)-, ent-or synstereochemistry.…”

Under Fire –simultaneous Volatilome and Transcriptome Analysis Unravels Fine-scale Responses of Tansy Chemotypes to Dual Herbivore Attack

“…Furthermore, we could detect one putative gene in the TPS-f group, which includes linalool synthases. The high homology of individual TPS genes to known and enzymatically characterised TPS does not imply that the enzymes annotated in tansy have the same biosynthesis products [8,[49][50][51]. In order to make a conclusive statement about the enzyme activity of the putative TPS, we are aware that each gene must be expressed heterologously and subjected to biochemical function analysis [52][53][54][55].…”

Genetic elucidation of complex biochemical traits mediating maize innate immunity

“…Terpenoids are the most structurally diverse class of plant specialized metabolites and are typically produced from the combined activities of terpene synthase (TPS) and cytochrome P450 monooxygenase (P450) enzymes 24, 25 . Known maize terpenoid antibiotics include α/β-costic acids, dolabralexins and kauralexins 18, 26, 27 .…”