| 1. |
- Zhou, Yongjin, 1984, et al.
(författare)
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Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 7, s. 11709-11709
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Tidskriftsartikel (refereegranskat)abstract
- Sustainable production of oleochemicals requires establishment of cell factory platform strains. The yeast Saccharomyces cerevisiae is an attractive cell factory as new strains can be rapidly implemented into existing infrastructures such as bioethanol production plants. Here we show high-level production of free fatty acids (FFAs) in a yeast cell factory, and the production of alkanes and fatty alcohols from its descendants. The engineered strain produces up to 10.4 g/L of FFAs, which is the highest reported titre to date. Furthermore, through screening of specific pathway enzymes, endogenous alcohol dehydrogenases and aldehyde reductases, we reconstruct efficient pathways for conversion of fatty acids to alkanes (0.8 mg /L) and fatty alcohols (1.5 g/L), to our knowledge the highest titres reported in S. cerevisiae. This should facilitate the construction of yeast cell factories for production of fatty acids derived products and even aldehyde-derived chemicals of high value.
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| 2. |
- Huang, Mingtao, 1984, et al.
(författare)
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Engineering the protein secretory pathway of Saccharomyces cerevisiae enables improved protein production
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:47, s. E11025-E11032
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Tidskriftsartikel (refereegranskat)abstract
- Baker’s yeast Saccharomyces cerevisiae is one of the most important and widely used cell factories for recombinant protein production. Many strategies have been applied to engineer this yeast for improving its protein production capacity, but productivity is still relatively low, and with increasing market demand, it is important to identify new gene targets, especially targets that have synergistic effects with previously identified targets. Despite improved protein production, previous studies rarely focused on processes associated with intracellular protein retention. Here we identified genetic modifications involved in the secretory and trafficking pathways, the histone deacetylase complex, and carbohydrate metabolic processes as targets for improving protein secretion in yeast. Especially modifications on the endosome-to-Golgi trafficking was found to effectively reduce protein retention besides increasing protein secretion. Through combinatorial genetic manipulations of several of the newly identified gene targets, we enhanced the protein production capacity of yeast by more than fivefold, and the best engineered strains could produce 2.5 g/L of a fungal α-amylase with less than 10% of the recombinant protein retained within the cells, using fed-batch cultivation.
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| 3. |
- Qin, Jiufu, 1985, et al.
(författare)
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Engineering yeast metabolism for the discovery and production of polyamines and polyamine analogues
- 2021
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Ingår i: Nature Catalysis. - : Springer Science and Business Media LLC. - 2520-1158. ; 4:6, s. 498-509
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Tidskriftsartikel (refereegranskat)abstract
- Structurally complex and diverse polyamines and polyamine analogues are potential therapeutics and agrochemicals that can address grand societal challenges, for example, healthy ageing and sustainable food production. However, their structural complexity and low abundance in nature hampers either bulk chemical synthesis or extraction from natural resources. Here we reprogrammed the metabolism of baker’s yeast Saccharomyces cerevisiae and recruited nature’s diverse reservoir of biochemical tools to enable a complete biosynthesis of multiple polyamines and polyamine analogues. Specifically, we adopted a systematic engineering strategy to enable gram-per-litre-scale titres of spermidine, a central metabolite in polyamine metabolism. To demonstrate the potential of our polyamine platform, various polyamine synthases and ATP-dependent amide-bond-forming systems were introduced for the biosynthesis of natural and unnatural polyamine analogues. The yeast platform serves as a resource to accelerate the discovery and production of polyamines and polyamine analogues, and thereby unlocks this chemical space for further pharmacological and insecticidal studies. [Figure not available: see fulltext.]
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