Methylotrophic yeasts for industrial biotechnology

Flow diagram of a future CO<sub>2</sub> utilization cascade. Using renewable energy, Carbon Capture and Utilization (CCU) technologies, and synthetic methylotrophy in yeasts, CO<sub>2</sub> can be regarded as an almost infinitely available raw material. CO<sub>2</sub> can be used to produce high-value chemicals with a broad marketing and application potential.
© Fraunhofer IGB
Flow diagram of a future CO2 utilization cascade. Using renewable energy, Carbon Capture and Utilization (CCU) technologies, and synthetic methylotrophy in yeasts, CO2 can be regarded as an almost infinitely available raw material. CO2 can be used to produce high-value chemicals with a broad marketing and application potential.

Methylotrophic yeasts for industrial biotechnology

A key to effectively limiting climate change lies in the development of sustainable production processes for the chemical industry. Against this background, research is focusing in particular on processes and process cascades based on the use of carbon dioxide (CO2) as a raw material.

New generation of biotechnological production processes: C1 intermediates produced electrochemically from CO2 as substrate

The starting point of such biotechnological processes is the heterogeneous or electrocatalytic conversion of CO2 to microbial C1 fermentation substrates such as methanol or formic acid. These substrates can be converted into biomass by methylotrophic microorganisms, including methylotrophic yeasts, but can also be converted into a variety of chemical compounds that can be used and marketed as feed additives, fine chemicals, polymer building blocks, or biofuels. Such approaches represent a new generation of biotechnological production processes that, in contrast to conventional processes, do not require the use of biogenic raw materials, such as sugar, and thus avoid a possible competitive situation with the production of food and animal feed.

Accordingly, the use of CO2 as a raw material as a central element of a circular and truly sustainable economy enables a pronounced scalability of production processes, without the ecological and socio-economic risks of intensified use of biomass and biogenic raw materials.

Utilization of C1 substrates with methylotrophic microorganisms

The central building block of these processes are methylotrophic microorganisms, which can be found in numerous types in nature. A limited number of methylotrophic metabolic pathways exist that enable their host organisms to utilize methanol, but within tight energetic constraints and evolutionarily optimized for biomass formation in niche ecological habitats. Resolving these metabolic constraints and optimizing the challenging genetic modification of naturally methylotrophic host organisms depict a central leitmotif of current research activities at the Straubing BioCat branch of Fraunhofer IGB.

Synthetic methylotrophy: Metabolic engineering for high-performance production strains

The focus is particularly on synthetic methylotrophy. This can be established by introducing the known enzymes involved or new, tailor-made synthetic metabolic pathways into conventionally and well understood as well as industrially used host organisms such as E. coli. The accompanying advance in knowledge of the use of these organisms allows more efficient and rapid development of high-performance production strains that meet industrial needs. Synthetic biology approaches can enable these synthetically methylotrophic microorganisms to produce a range of basic chemicals based on CO2.

Compartmentalization in yeasts allows metabolism of cytotoxins such as methanol

As relevant platform organisms for industry, yeasts in particular offer excellent potential due to increased tolerance to low pH and the availability of established methods for genetic modification. Another advantage of synthetic methylotrophy in yeasts is the ability of these organisms to limit the formation of toxic intermediates and associated metabolic reactions in organelles such as peroxisomes. This intracellular and spatial compartmentalization can be used to engineer robust synthetic methylotrophic yeasts capable of efficiently utilizing methanol. Thus, synthetic methylotrophic yeasts represent an extremely exciting and versatile tool in biotechnology that can reduce dependence on fossil resources and ultimately contribute to the establishment of a sustainable circular economy. The Straubing branch of Fraunhofer IGB is working intensively on the development of synthetic methylotrophic yeasts as biotechnological production strains.

Publication

The biotechnological approaches pursued at Fraunhofer IGB’s BioCat branch in Straubing have been published in the journal "Trends in Biotechnology". In particular, the paper describes the potential and possibilities of using synthetic methylotrophic yeasts as production strains in industrial biotechnology.

Jonathan Thomas Fabarius, Vanessa Wegat, Arne Roth, Volker Sieber (2020) Synthetic Methylotrophy in Yeasts: Towards a Circular Bioeconomy, Trends in Biotechnology, Pages No. 1-11. https://doi.org/10.1016/j.tibtech.2020.08.008