Biosynthetic Origin of Complex Terpenoid Mixtures by Multiproduct Enzymes, Metal Cofactors, and Substrate Isomers

Abstract

Terpenoids form a substantial portion of chemical diversity in nature. The enormous terpenoid diversity of more than 80,000 compounds is supported by the multisubstrate and multiproduct nature of certain enzymes from the various terpene synthases and terpene cyclases. These highly versatile enzymes are not only able to accept multiple substrates in their active site, but also simultaneously catalyze multiple reactions to the resultant multiple products. Interestingly, apart from the substrates and catalytic mechanisms, multiple regulation factors are able to alter the product profile of multiproduct terpene synthases. Simple variations in cellular conditions by changes in metal cofactors, assay pH, temperature and substrate geometry lead to significant shifts in product profiles. Switch in substrate stereochemistry for multiproduct terpene synthases in some case shows enhanced biocatalysis and in others initiates even a novel cyclization cascade. Hence, organisms can get access to a greater chemodiversity and avoid the expensive process of developing new biocatalysts just by simple changes in the cellular environment. This possibility of modulating chemical diversity provides immobile plants in the same generation access to an enhanced chemical arsenal for defense and communication by simply altering cofactors, pH level, and temperature and substrate geometry.