Developing a yeast cell factory for the production of terpenoids

Abstract

Technological developments over the past century have made microbes the work-horses of large scale industrial production processes. Current efforts focus on the metabolic engineering of microbial strains to produce high levels of desirable end-products. The arsenal of the contemporary metabolic engineer contains tools that allow either targeted rational interventions or global screens that combine classical approaches with -omics technologies. Production of terpenoids in S. cerevisiae presents a characteristic example of contemporary biotechnology that integrates all the variety of novel approaches used in metabolic engineering. Terpenoids have attracted significant interest as pharmaceuticals, flavour and fragrance additives, and, more recently, biofuels. The ongoing metabolic engineering efforts, combined with the continuously increasing number of terpene biosynthetic enzymes discovered will enable the economical and environmentally friendly production of a wide range of compounds.

Figure 1

Synopsis of terpene biosynthesis in yeast indicating the genes involved and the metabolic engineering interventions employed. Upregulated yeast genes indicated indicated in green, downregulated yeast genes in red. Genes whose products have been fused or attached to a synthetic protein scaffold are denoted with supersripted (f). Enzymes with product yield or specificity improved or altered by protein engineering are indicated by superscripted (e). (CPP, copalyl diphosphate; CDS, copalyl diphosphate synthase; DTS, diterpene synthase; MTS, monoterpene synthase; SeACS(L641P), Salmonella enterica acetyl-CoA synthase mutant L641P; AtoB, acetoacetyl-CoA synthase/thiolase).