The Glyoxylate-Serine Pathway Enables Conversion of  &lt;i&gt;Saccharomyces cerevisiae&lt;/i&gt; to a Synthetic Methylotroph

Zhan, Cheng; Li, Xiaowei; Baidoo, Edward E. K.; Yang, Yankun; Sun, Yan; Wang, Shijie; Wang, Yanyan; Wang, Guokun; Nielsen, Jens; Keasling, Jay D.; Chen, Yun; Bai, Zhonghu

doi:10.2139/ssrn.3855737

Cited by 9 publications

(44 citation statements)

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“…As advantageous for methanol metabolism, the peroxisomal compartmentalization strategy has been employed to enhance methanol utilization in synthetic methylotroph. 37 This investigation demonstrates the potential of a compartmentalized optimization for the future engineering of the methanol pathway in P. pastoris.…”

Section: ■ Current Breakthroughs In Understandingmentioning

confidence: 69%

Methylotrophy of Pichia pastoris: Current Advances, Applications, and Future Perspectives for Methanol-Based Biomanufacturing

Guo

Liao

Wang

et al. 2022

ACS Sustainable Chem. Eng.

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Methanol, a nonfood C1 feedstock that could be produced either from fossil or potentially renewable raw materials has recently attracted much attention as a very promising feedstock alternative to sugar-based raw materials for biomanufacturing. Methylotrophic cell factories that could efficiently convert methanol to value-added products are highly desired for methanol-based biomanufacturing. Pichia pastoris shows significant industrial promise for methanol bioconversion due to its advantage in the methanol utilization rate compared to other native or synthetic methylotrophs. Here, we review the current understanding of methanol metabolism of P. pastoris, discuss the important factors that influence the methanol utilization ability of P. pastoris, and summarize the recent advances in the application of engineered P. pastoris to produce various chemicals from methanol. We also discuss future challenges and possible solutions to develop P. pastoris as an efficient cell factory used for methanol-based biomanufacturing.

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Section: ■ Current Breakthroughs In Understandingmentioning

confidence: 69%

Methylotrophy of Pichia pastoris: Current Advances, Applications, and Future Perspectives for Methanol-Based Biomanufacturing

Guo

Liao

Wang

et al. 2022

ACS Sustainable Chem. Eng.

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“…The assimilated methanol was converted to proteinogenic amino acids derived from the serine pathway and glycolysis and also likely energy in the NADH format through the dramatically upregulated formaldehyde dissimilation (Figures 5 and 7). Formaldehyde dissimilation, either via formate dehydrogenation or serine pathway, was extensively upregulated in both natural methylotrophic K. phaffii (even though it could inhibit the flux through the TCA cycle 27 ) and synthetic methylotrophic S. cerevisiae 22 when both strains were cultivated in methanol. These results altogether suggest that formaldehyde dissimilation is a rapid approach to formaldehyde detoxification and energy supply (NADH); when necessary, its upregulation would serve as a natural solution of a cell to enable a methanoldependent growth.…”

Section: ■ Discussionmentioning

confidence: 99%

“…phaffii (even though it could inhibit the flux through the TCA cycle) and synthetic methylotrophic S. cerevisiae when both strains were cultivated in methanol. These results altogether suggest that formaldehyde dissimilation is a rapid approach to formaldehyde detoxification and energy supply (NADH); when necessary, its upregulation would serve as a natural solution of a cell to enable a methanol-dependent growth.…”

Section: Discussionmentioning

confidence: 99%

“…21 During the preparation of this manuscript, a preprint of a study was published on creating synthetic methylotrophy in S. cerevisiae through the construction of the methanol assimilation pathway in peroxisome and laboratory evolution. 22 Nonconventional yeast Yarrowia lipolytica is a platform cell factory for lipid-derived chemicals and fuels, single-cell proteins, enzymes, and nutraceuticals. 23 It can assimilate various carbon sources naturally or upon engineering 24 and, therefore, has a plastic metabolism for methanol assimilation.…”

Section: ■ Introductionmentioning

confidence: 99%

“…During the preparation of this manuscript, a preprint of a study was published on creating synthetic methylotrophy in S. cerevisiae through the construction of the methanol assimilation pathway in peroxisome and laboratory evolution …”

Section: Introductionmentioning

confidence: 99%

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Engineering Yeast Yarrowia lipolytica for Methanol Assimilation

et al. 2021

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Conferring methylotrophy on industrial microorganisms would enable the production of diverse products from one-carbon feedstocks and contribute to establishing a low-carbon society. Rebuilding methylotrophs, however, requires a thorough metabolic refactoring and is highly challenging. Only recently was synthetic methylotrophy achieved in model microorganismsEscherichia coli and baker’s yeast Saccharomyces cerevisiae. Here, we have engineered industrially important yeast Yarrowia lipolytica to assimilate methanol. Through rationally constructing a chimeric assimilation pathway, rewiring the native metabolism for improved precursor supply, and laboratory evolution, we improved the methanol assimilation from undetectable to a level of 1.1 g/L per 72 h and enabled methanol-supported cellular maintenance. By transcriptomic analysis, we further found that fine-tuning of methanol assimilation and ribulose monophosphate/xylulose monophosphate (RuMP/XuMP) regeneration and strengthening formate dehydrogenation and the serine pathway were beneficial for methanol assimilation. This work paves the way for creating synthetic methylotrophic yeast cell factories for low-carbon economy.

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Strategies to increase the robustness of microbial cell factories

Xu,

Lin,

Zhang

et al. 2024

Adv. Biotechnol.

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Engineering microbial cell factories have achieved much progress in producing fuels, natural products and bulk chemicals. However, in industrial fermentation, microbial cells often face various predictable and stochastic disturbances resulting from intermediate metabolites or end product toxicity, metabolic burden and harsh environment. These perturbances can potentially decrease productivity and titer. Therefore, strain robustness is essential to ensure reliable and sustainable production efficiency. In this review, the current strategies to improve host robustness were summarized, including knowledge-based engineering approaches, such as transcription factors, membrane/transporters and stress proteins, and the traditional adaptive laboratory evolution based on natural selection. Computation-assisted (e.g. GEMs, deep learning and machine learning) design of robust industrial hosts was also introduced. Furthermore, the challenges and future perspectives on engineering microbial host robustness are proposed to promote the development of green, efficient and sustainable biomanufacturers.

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The Glyoxylate-Serine Pathway Enables Conversion of <i>Saccharomyces cerevisiae</i> to a Synthetic Methylotroph

Cited by 9 publications

References 0 publications

Methylotrophy of Pichia pastoris: Current Advances, Applications, and Future Perspectives for Methanol-Based Biomanufacturing

Methylotrophy of Pichia pastoris: Current Advances, Applications, and Future Perspectives for Methanol-Based Biomanufacturing

Engineering Yeast Yarrowia lipolytica for Methanol Assimilation

Strategies to increase the robustness of microbial cell factories

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