Opinion
Special Issue: Bioconversion of C1 Products and Feedstocks
Synthetic Methylotrophy in Yeasts: Towards a Circular Bioeconomy

https://doi.org/10.1016/j.tibtech.2020.08.008Get rights and content

Highlights

  • Synthetic methylotrophic yeasts possess advantageous properties and exploitable biotechnological potential.

  • Microbial methylotrophy is a powerful and versatile pillar of a future circular bioeconomy.

  • Utilizing CCU-derived C1 chemicals as a fermentation feedstock for climate-neutral bioprocesses offers various application potentials.

  • Connecting chemistry, electrochemistry, and bioengineering is the starting point to CO2-based value chains.

  • The development of synthetic methylotrophs is a key driver for the sustainable production of value-added chemicals and renewable fuels using CO2 as an abundant resource.

  • Yeasts cover vast product ranges (fatty acids, organic and amino acids, vitamins, modified proteins) and provide additional benefits over prokaryotes, such as their tolerance towards acidic conditions or their compartmentalization in organelles.

Mitigating climate change is a key driver for the development of sustainable and CO2-neutral production processes. In this regard, connecting carbon capture and utilization processes to derive microbial C1 fermentation substrates from CO2 is highly promising. This strategy uses methylotrophic microbes to unlock next-generation processes, converting CO2-derived methanol. Synthetic biology approaches in particular can empower synthetic methylotrophs to produce a variety of commodity chemicals. We believe that yeasts have outstanding potential for this purpose, because they are able to separate toxic intermediates and metabolic reactions in organelles. This compartmentalization can be harnessed to design superior synthetic methylotrophs, capable of utilizing methanol and other hitherto largely disregarded C1 compounds, thus supporting the establishment of a future circular economy.

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

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