Abstract
Terpenoids are a diverse group of over 55,000 compounds with potential applications as advanced fuels, bulk and fine chemicals, pharmaceutical ingredients, agricultural chemicals, etc. To facilitate their bio-based production, there is a need for plug-and-play hosts, capable of high-level production of different terpenoids. Here we engineer Yarrowia lipolytica platform strains for the overproduction of mono-, sesqui-, di-, tri-, and tetraterpenoids. The monoterpene platform strain was evaluated by expressing Perilla frutescens limonene synthase, which resulted in limonene titer of 35.9 mg/L and was 100-fold higher than when the same enzyme was expressed in the strain without mevalonate pathway improvement. Expression of Callitropsis nootkatensis valencene synthase in the sesquiterpene platform strain resulted in 113.9 mg/L valencene, an 8.4-fold increase over the control strain. Platform strains for production of squalene, complex triterpenes, or diterpenes and carotenoids were also constructed and resulted in the production of 402.4 mg/L squalene, 22 mg/L 2,3-oxidosqualene, or 164 mg/L β-carotene, respectively. The presented terpenoid platform strains can facilitate the evaluation of terpenoid biosynthetic pathways and are a convenient starting point for constructing efficient cell factories for the production of various terpenoids. The platform strains and exemplary terpenoid strains can be obtained from Euroscarf.
Highlights
Terpenoids comprise the largest class of secondary metabolites; many have biological activity and are used as nutra- and pharmaceutical agents and ingredients for cosmetics or food (Tetali, 2018)
Two key strategies were implemented for all platform strains: improvement of the precursor acetyl-coenzyme A (CoA) pool and upregulation of the MVA-pathway to improve the accumulation of isopentyl diphosphate (IPP)/DMAPP (Figure 1)
Truncated versions of Hmgp have been used in S. cerevisiae, studies indicate that the non-truncated version is superior for terpenoid production in Y. lipolytica
Summary
Terpenoids comprise the largest class of secondary metabolites; many have biological activity and are used as nutra- and pharmaceutical agents and ingredients for cosmetics or food (Tetali, 2018). Several terpenoids, such as farnesene and bisabolene, have been developed as advanced biofuels. Terpenoids are categorized depending on the number of carbon atoms forming the core skeleton. Other terpenoid classes include hemiterpenoids (C5) and sesterterpenoids (C25) (Janocha et al, 2015). The core hydrocarbon skeletons assembled from isoprene units are commonly modified by enzymes like cytochromes P450, hydrogenases, methyltransferases, and glycosyltransferases. Terpenoids content in natural sources is typically low and extraction
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