Construction and optimization of Saccharomyces cerevisiae for synthesizing forskolin

Ju, Haiyan; Zhang, Chuanbo; He, Shifan; Nan, Weihua; Lu, Wenyu

doi:10.1007/s00253-022-11819-z

Cited by 7 publications

(9 citation statements)

References 49 publications

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“…Zhao et al fused protopanaxadiol synthase (PPDS) with ATR1, using “GSTSSGSG”, “GSTSSG”, or “GGG” as the linkers, to construct the self-sufficient PPDS-ATR1 fusion enzymes. In their study, the catalytic capacities of the fusion enzymes were enhanced by 4.5-fold with the GGG . D’Adamo et al found that fusion of Mt CYP716A12 and Mt CPR via the linker GSTSSGSG increased the conversion rate of lupeol to betulin .…”

Section: Resultsmentioning

confidence: 99%

Reconstitution and Optimization of the Marmesin Biosynthetic Pathway in Yeast

Wang,

Zhou,

Wang

et al. 2023

ACS Synth. Biol.

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Marmesin is essential in plant defense systems and exhibits various biological activities. In this study, we reconstituted the marmesin biosynthetic pathway in the Saccharomyces cerevisiae BY4741 chassis. We engineered the aromatic amino acid (AAA) biosynthetic pathways by introducing Escherichia coli-derived ppsA to improve the availability of the AAA precursor phosphoenolpyruvate, overexpressing the feedback inhibition resistance genes ARO4 K229L and ARO7 G141S to direct the metabolic flux toward the tyrosine branch, and deleting ARO10, PDC5, and PDC6 to reduce the byproducts from the Ehrlich pathway. The umbelliferone 6-dimethylallyltransferase (U6DT) and marmesin synthase (MS) involved in marmesin synthesis were optimized to increase marmesin production. Marmesin production was improved by truncating the transmembrane domains of PcU6DT, FcMS, and AtCPR1 and increasing the copy numbers of the genes encoding the truncated enzymes. Finally, a marmesin titer of 27.7 mg/L was obtained in shake flasks using the engineered yeast strain MU5. The constructed marmesin-producing strain provides the foundation for the green and large-scale production of pharmaceutically important furanocoumarins.

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Section: Resultsmentioning

confidence: 99%

Reconstitution and Optimization of the Marmesin Biosynthetic Pathway in Yeast

Wang,

Zhou,

Wang

et al. 2023

ACS Synth. Biol.

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“…Expansion of the ER can increase its capacity to promote the expression of ERlocalized proteins and boost terpene accumulation (Kim et al, 2019). Furthermore, suppressing the dephosphorylation and activation of PAH1 can enhance membrane protein productivity and increase the surface area of the ER membrane (Ju et al, 2022). The disruption of PAH1 resulted in a decreased number of LDs, accompanied by the accumulation of neutral lipids in the ER (Adeyo et al, 2011).…”

Section: Er and Membrane Engineeringmentioning

confidence: 99%

Compartmentalization engineering of yeasts to overcome precursor limitations and cytotoxicity in terpenoid production

Chen

Xiao

Yao

et al. 2023

Front. Bioeng. Biotechnol.

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Metabolic engineering strategies for terpenoid production have mainly focused on bottlenecks in the supply of precursor molecules and cytotoxicity to terpenoids. In recent years, the strategies involving compartmentalization in eukaryotic cells has rapidly developed and have provided several advantages in the supply of precursors, cofactors and a suitable physiochemical environment for product storage. In this review, we provide a comprehensive analysis of organelle compartmentalization for terpenoid production, which can guide the rewiring of subcellular metabolism to make full use of precursors, reduce metabolite toxicity, as well as provide suitable storage capacity and environment. Additionally, the strategies that can enhance the efficiency of a relocated pathway by increasing the number and size of organelles, expanding the cell membrane and targeting metabolic pathways in several organelles are also discussed. Finally, the challenges and future perspectives of this approach for the terpenoid biosynthesis are also discussed.

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“…Reducing enzyme activity can also be achieved by adding terbinafine, a noncompetitive enzyme inhibitor. The farnesol synthesis pathway is another endogenous sesquiterpene pathway that competes for FPP in S. cerevisiae , and the knockout of key genes, encoding lipid phosphate phosphatase (LPP1) and diacylglycerol pyrophosphate phosphatase (DPP1), can also effectively reduce FPP consumption to improve terpene synthesis. ,, …”

Section: Pathway Engineering For Terpene Biosynthesis In Yeastsmentioning

confidence: 99%

“…The farnesol synthesis pathway is another endogenous sesquiterpene pathway that competes for FPP in S. cerevisiae, and the knockout of key genes, encoding lipid phosphate phosphatase (LPP1) and diacylglycerol pyrophosphate phosphatase (DPP1), can also effectively reduce FPP consumption to improve terpene synthesis. 102,113,114 Nonetheless, the overproduction of monoterpenes is still hindered by intrinsic factors, because native ERG20 is a bifunctional enzyme that not only catalyzes the condensation of IPP and DMAPP to form the monoterpene synthase substrate GPP but also favors the synthesis of FPP, which undoubtedly weakens the ability of GPP to compete for precursors. By contrast, the mutant ERG20 F96W−N127W in S. cerevisiae as well as ERG20 F88W−N119W in Y. lipolytica showed great preference for GPP production, with great potential for the synthesis of monoterpenes and higher GPP supply.…”

Section: Downregulating Competingmentioning

confidence: 99%

Advances in Metabolic Engineering Paving the Way for the Efficient Biosynthesis of Terpenes in Yeasts

Cui

Mai

et al. 2022

J. Agric. Food Chem.

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Terpenes are a large class of secondary metabolites with diverse structures and functions that are commonly used as valuable raw materials in food, cosmetics, and medicine. With the development of metabolic engineering and emerging synthetic biology tools, these important terpene compounds can be sustainably produced using different microbial chassis. Currently, yeasts such as Saccharomyces cerevisiae and Yarrowia lipolytica have received extensive attention as potential hosts for the production of terpenes due to their clear genetic background and endogenous mevalonate pathway. In this review, we summarize the natural terpene biosynthesis pathways and various engineering strategies, including enzyme engineering, pathway engineering, and cellular engineering, to further improve the terpene productivity and strain stability in these two widely used yeasts. In addition, the future prospects of yeast-based terpene production are discussed in light of the current progress, challenges, and trends in this field. Finally, guidelines for future studies are also emphasized.

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Construction and optimization of Saccharomyces cerevisiae for synthesizing forskolin

Cited by 7 publications

References 49 publications

Reconstitution and Optimization of the Marmesin Biosynthetic Pathway in Yeast

Reconstitution and Optimization of the Marmesin Biosynthetic Pathway in Yeast

Compartmentalization engineering of yeasts to overcome precursor limitations and cytotoxicity in terpenoid production

Advances in Metabolic Engineering Paving the Way for the Efficient Biosynthesis of Terpenes in Yeasts

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