Production of resveratrol from tyrosine in metabolically engineered Saccharomyces cerevisiae

Advances in Metabolic Engineering of Saccharomyces cerevisiae for the Production of Industrially and Clinically Important Chemicals

“…Glutathione Overexpression of YAP1 [58] Manipulation of the sulphate assimilation pathway by overexpressing MET14 and MET16 [59] Improved oxidized glutathione production by overexpression of GSH1, GSH2, and ERV1 and the deletion of GLR1 [60] Adaptive laboratory evolution in the presence of increasing levels of acrolein and screening for enhanced glutathione production [61] Whole-genome engineering via genome shuling and screening for enhanced glutathione production [62] Artemisinin/artemisinic acid Reconstruction of the complete biosynthetic pathway of artemisinic acid, including the three-step oxidation of amorphadiene to artemisinic acid by expression of CYP71AV1, CPR1, CYB5, ADH1 and ALDH1 from Artemisia annua [48] Taxol/taxadiene Expression of a truncated version of the endogenous tHMG1 and GGPPS from Taxus chinensis or Sulfolobus acidocaldarius together with TDC1 from T. chinensis [66] Prediction of the eiciency of diferent GGPPS enzymes via computer aided protein modelling [67] Forskolin Expression of a promiscuous cytochrome P450 from Salvia pomifera [68] Polyketides Heterologous expression of 6-MSA synthase gene from Penicillium patulum together with PPTases from either Bacillus subtilis or Aspergillus nidulans [69] Construction of polyketide precursor pathways by expressing prpE from Salmonella typhimurium and PCC pathway from Streptomyces coelicolor [70] Enhanced cofactor supply by expressing 2-PS from Gerbera hybrida [71] Resveratrol Reconstruction of a de novo pathway by expressing TAL from Herpetosiphon aurantiacus, 4-CL1 from Arabidopsis thaliana and VST1 from Vitis vinifera [49] Expression of 4CL1 from A. thaliana and STS from Arachis hypogaea [73] Expression of PAL from Rhodosporidium toruloides, C4H and 4-CL1 from A. thaliana, and STS from A. hypogaea [74] Expression of 4-coumaroyl-coenzyme A ligase (4CL1) from A. thaliana and stilbene synthase (STS) from V. vinifera [75] Overexpression of the resveratrol biosynthesis pathway, enhancement of P450 activity, increasing the precursor supply for resveratrol synthesis via phenylalanine pathway [76] Dihydrochalcones Expression of the heterologous pathway genes in a TSC13-overexpressing S. cerevisiae strain [78] Alkaloids Expression of 14 monoterpene indole alkaloid pathway genes from Catharanthus roseus and enhanced secondary metabolism to produce strictosidine de novo [79] Construction of the complete de novo biosynthetic pathway to norcoclaurine by expressing a mammalian TyrH enzyme and DODC from Pseudomonas putida, along with four genes required for biosynthesis of its electron carrier cosubstrate …”

“…Resveratrol is a polyketide derivative with potent antioxidant properties and it has been recently brought to market as a bio-product [72]. Earlier reports on the production of resveratrol were based on bioconversion of aromatic precursors such as p-coumaric acid and tyrosine by engineered S. cerevisiae strains [73,74]. The highest resveratrol titer achieved by using this approach was obtained by an engineered industrial Brazilian S. cerevisiae strain, at a titer of 391 mg/L resveratrol on complex medium supplemented with p-coumaric acid [75].…”

Heterologous Production of Curcuminoids

“…C4H from A. thaliana and Glycine max was successfully cloned and expressed in S. cerevisiae in several studies (123,127,128,131). Although C4H was functionally expressed, it was still a rate-limiting step.…”

“…Saccharomyces cerevisiae, which is also easy to grow and manipulate and is well characterized, has been used only to produce other polyketides, such as resveratrol, naringenin, and pinocembrim, among others (Table 3) (115,(123)(124)(125)(126)(127)(128)(129)(130)(131)(132). However, as a eukaryote, S. cerevisiae presents some unique advantages over E. coli for the design and construction of a biosynthetic pathway for the production of curcuminoids.…”

“…Other enzymes from the phenylpropanoid pathway, such as PAL from Rhodosporidium toruloides and a Populus hybrid, RsTAL, RcTAL, RgTAL, 4CL2 from Nicotiana tabacum, 4CL216 from a Populus hybrid, 4CL from G. max, Le4CL1, At4CL1, and Pc4CL2, were also successfully expressed in yeast (115,(123)(124)(125)(126)(127)(128)(129)(130)(131)(132)174). The At4CL1 gene seems to be the best option to produce resveratrol in S. cerevisiae (139), since its yield was more than 65 times higher than when using 4CL216 from Populus hybrid (125) and 4CL2 from Nicotiana tabacum (124) in similar experiments using Vitis vinifera STS (stilbene synthase).…”