Trends in Biotechnology
OpinionSpecial Issue: Bioconversion of C1 Products and FeedstocksSynthetic Methylotrophy in Yeasts: Towards a Circular Bioeconomy
Section snippets
Methylotrophy as a Key Driver of Circular Economy
The ever-increasing human emission of greenhouse gases, in particular CO2, has changed the planet’s climate [1], and solutions to counteract their enormous negative impacts are intensively sought. Technologies that use CO2 from renewable sources as a feedstock, so-called carbon capture and utilization (CCU) (see Glossary) technologies, represent a powerful approach for closing the carbon cycle and realizing a sustainable circular economy [1., 2., 3.]. One option is the conversion of CO2 and
Advantages and Challenges of Yeast in Modern Biotechnology
Previous investigations have shown that yeasts provide a number of advantageous properties, making them ideal hosts for biotechnological production processes [26,27]. Protein expression is excellent in terms of increased gene expression levels, protein assembly and folding, plus post-translational modifications [28]. The most striking advantage of yeasts is the enhanced tolerance towards extreme (acidic and basic) pH conditions [29]. Especially, for the production of organic acids, hosts with a
Methylotrophy Is a Challenge for the Cell
The XuMP pathway in methylotrophic yeasts (Figure 2) uses an unspecific O2-dependent alcohol-oxidase, forming the toxic intermediates formaldehyde and H2O2. In all eukaryotes, the peroxisomes prevent the distribution of toxic H2O2 into the cytoplasm by separation of alcohol-oxidase together with catalase [37]. Furthermore, cytosolic H2O2 is detoxified by utilization of the glutathione redox system. Formaldehyde is assimilated with xylulose-5-phosphate by peroxisomal dihydroxyacetone-synthase
Current Advances in Synthetic Methylotrophy
An existing solution to improve the performance of methylotrophy is genetic engineering. Metabolic engineering combined with synthetic biology and systems biology approaches to achieve superior tailor-made microbial cell factories is especially promising [44]. To adapt and improve heterologous production capabilities of methylotrophic organisms, three engineering strategies are envisioned: (i) engineering methylotrophic bacteria or methylotrophic yeasts for the efficient production of target
New Application Opportunities of Synthetic Methylotrophic Yeasts
The outstanding properties of yeasts to deal with C1 metabolism and associated toxic compounds is an opportunity to harness other, so far, disregarded and challenging substrates. The valorization of such challenging feedstocks can support the development of a new generation of microbial cell factories. Therefore, it is promising to consider C1 feedstocks alongside the more common ones. Most obvious is the inclusion of C1 chemicals supplying at least partially the other major elements of life:
Concluding Remarks
Concentration of atmospheric greenhouse gases can be reduced by innovative CO2-utilization technologies, which represent a powerful approach to establish a synthetic carbon cycle in a circular economy. Particularly encouraging are fermentation processes for utilization of C1 feedstocks derived by (electro-)chemical CO2 reduction like methanol and formic acid, which rely on efficient tailor-made methylotrophic microbial cell factories to produce desired compounds, goods, and chemicals. The
Acknowledgments
This work was funded partially by the Bavarian State Ministry of Economic Affairs and Media, Energy and Technology and partially from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 679050 (project Celbicon).
Glossary
- C1 feedstock
- gaseous (e.g., carbon dioxide or methane) or liquid chemicals (e.g., formate, formaldehyde, and methanol), which contain only a single carbon atom and can be used as substrates for microbial fermentation.
- Carbon capture and utilization (CCU)
- emerging process concepts that target the capture of carbon dioxide and its further usage as carbonaceous feedstock in the synthesis of fuels and value-added chemical products.
- Formatotrophy
- microorganisms with natural capabilities to utilize
References (75)
- et al.
CO2 utilization: developments in conversion processes
Petroleum
(2017) The formate bio-economy
Curr. Opin. Chem. Biol.
(2016)A review of research progress on heterogeneous catalysts for methanol synthesis from carbon dioxide hydrogenation
Catal. Today
(2019)Comparative energetic assessment of methanol production from CO2: chemical versus electrochemical process
Appl. Energy
(2016)- et al.
Processes for the synthesis of liquid fuels from CO2 and marine energy
Chem. Eng. Res. Des.
(2006) - et al.
Current trends in methylotrophy
Trends Microbiol.
(2018) - et al.
Single cell proteins: a new source of animal feeds
Endeavour
(1978) Grand research challenges for sustainable industrial biotechnology
Trends Biotechnol.
(2019)Engineering of non-conventional yeasts for efficient synthesis of macromolecules: the methylotrophic genera
Biochimie
(2002)Engineered monoculture and co-culture of methylotrophic yeast for de novo production of monacolin J and lovastatin from methanol
Metab. Eng.
(2018)
The significance of peroxisomes in methanol metabolism in methylotrophic yeast
Biochim. Biophys. Acta Mol. Cell Res.
Synthetic methylotrophy: a practical solution for methanol-based biomanufacturing
Trends Biotechnol.
Systems metabolic engineering strategies: integrating systems and synthetic biology with metabolic engineering
Trends Biotechnol.
Metabolomics-driven approach to solving a CoA imbalance for improved 1-butanol production in Escherichia coli
Metab. Eng.
Utilizing an endogenous pathway for 1-butanol production in Saccharomyces cerevisiae
Metab. Eng.
Renewable methanol and formate as microbial feedstocks
Curr. Opin. Biotechnol.
Engineering Corynebacterium glutamicum for methanol-dependent growth and glutamate production
Metab. Eng.
Metabolic construction strategies for direct methanol utilization in Saccharomyces cerevisiae
Bioresour. Technol.
Methanogenic degradation of tetramethylammonium hydroxide by Methanomethylovorans and Methanosarcina
J. Hazard. Mater.
Metabolic engineering of Yarrowia lipolytica for industrial applications
Curr. Opin. Biotechnol.
Exceptional solvent tolerance in Yarrowia lipolytica is enhanced by sterols
Metab. Eng.
The threat to climate change mitigation posed by the abundance of fossil fuels
Clim. Policy
A warm welcome for alternative CO2 fixation pathways in microbial biotechnology
Microb. Biotechnol.
Integrated CO2 capture and conversion to formate and methanol: connecting two threads
Acc. Chem. Res.
Methanol as carbon substrate in the bio-economy: metabolic engineering of aerobic methylotrophic bacteria for production of value-added chemicals
Biofuels Bioprod. Bior.
Experimental parameters affecting the photocatalytic reduction performance of CO2 to methanol: a review
Int. J. Energy Res.
A review on recent advances for electrochemical reduction of carbon dioxide to methanol using metal–organic framework (MOF) and non-MOF catalysts: challenges and future prospects
ACS Sustain. Chem. Eng.
How half a century of research was required to understand bacterial growth on C1 and C2 compounds; the story of the serine cycle and the ethylmalonyl-CoA pathway
Sci. Prog.
The potential application of Cupriavidus necator as polyhydroxyalkanoates producer and single cell protein: a review on scientific, cultural and religious perspectives
Appl. Food Biotechnol.
Chemical production from methanol using natural and synthetic methylotrophs
Biotechnol. J.
Current advance in bioconversion of methanol to chemicals
Biotechnol. Biofuels
Paris Climate Agreement passes the cost-benefit test
Nat. Commun.
The phylogenetic extent of metabolic enzymes and pathways
Genome Res.
Methylotrophs in natural habitats: current insights through metagenomics
Appl. Microbiol. Biotechnol.
Review: methylotrophic yeasts as factories for the production of foreign proteins
Yeast
Recombinant dragline silk-like proteins-expression and purification
AATCC Rev.
D-Xylose consumption by nonrecombinant Saccharomyces cerevisiae: a review
Yeast
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2022, Current Opinion in BiotechnologyCitation Excerpt :Methanotrophs can convert methane (CH4), an abundant carbon resource and potent greenhouse gas, into protein (for animal feed) or polyhydroxyalkanoates [3–5]. Methanol (CH3OH) and formic acid (CHOOH) are also emerging as attractive feedstocks, given recent progress in development of efficient catalytic processes for their production directly from CO2 using either renewable electricity or renewable hydrogen [6–11]. A key advantage of microbial conversion of these feedstocks is the high carbon yield, low energy input and high selectivity attainable with biological catalysts.
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