Engineering yeast metabolism for production of terpenoids for use as perfume ingredients, pharmaceuticals and biofuels

Abstract

Terpenoids represent a large class of natural products with significant commercial applications. These chemicals are currently mainly obtained through extraction from plants and microbes or through chemical synthesis. However, these sources often face challenges of unsustainability and low productivity. In order to address these issues, Escherichia coli and yeast have been metabolic engineered to produce non-native terpenoids. With recent reports of engineering yeast metabolism to produce several terpenoids at high yields, it has become possible to establish commercial yeast production of terpenoids that find applications as perfume ingredients, pharmaceuticals and advanced biofuels. In this review, we describe the strategies to rewire the yeast pathway for terpenoid biosynthesis. Recent advances will be discussed together with challenges and perspectives of yeast as a cell factory to produce different terpenoids.

Stepwise engineering ofSaccharomyces cerevisiaeto produce (+)-valencene and its related sesquiterpenes

“…12 There are many discussions about terpenoid production through metabolic engineering of S. cerevisiae at hierarchical levels of genetic manipulation tools, biological parts, pathways, organelles and systems. 10,[12][13][14][15] Although signicant progresses have been achieved in the past decades, there are still a lot of efforts to be made.…”

Strategies for the production of biochemicals in bioenergy crops

“…Although these common precursors (e.g., IPP, GPP, FPP, and GGPP) are synthesized by the two distinct pathways, they can be transported freely to different cellular compartments. For higher carbon skeletons of terpenes such as triterpenes and tetraterpenes, two molecules of FPP or GGPP are typically dimerized to form the precursors squalene (C 30 ) and phytoene (C 40 ), respectively [152] (Fig. 3).…”

“…With recent advancements in plant synthetic biology, implementation in crops of multigene isoprenoid metabolic pathways to develop biofuels and bioproducts at industrial scale is becoming attainable [200][201][202]. The wondrous diversity and structural richness of isoprenoid molecules from plants provide a plethora of potent and useful target compounds, especially for advanced biofuels and value-added bioproducts [152,[203][204][205][206]. In relation to bioenergy crops, several efforts have been made to elucidate the genetic components that influence terpene yields, as well as to develop biomass pretreatment methods for simultaneous extraction of both terpenes and fermentable sugars [207,208].…”

Polymers of Limonene Oxide and Carbon Dioxide: Polycarbonates of the Solar Economy

“…The first approach attempted was to use engineered microorganisms as a cell factory to produce terpenoids from cheap and readily available glucose. [25] However, whereas engineering yeast metabolism has been successful to produce several terpenoids in such high yield to become commercial, [26] limonene is highly toxic to microbes limiting its concentration in fermentation broths to very low levels (i.e. 2.7 g/L of l-limonene over recombinant Escherichia coli from glycerol as carbon source).…”