A synthetic yeast methanotroph for methane based sustainable biomanufacturing - SynYeast

Methane, the principal component of natural gas, is a powerful greenhouse gas driving climate change. Recent rises in global methane emission and the abundance of natural gas reserves have prompted interest in exploiting this one carbon compound as an industrial feedstock for bioproduction of liquid fuels and value-added chemicals. However, no direct methane to methanol conversion process have been commercialized at industrial scale. Bio-based manufacturing could provide novel solutions. The particulate methane monooxygenase (pMMO) found in methanotrophic bacteria is a selective catalyst for methane activation and conversion to methanol under mild conditions. Hence, much focus has been on heterologous expression of this enzyme in platform strains like E. coli to develop 'synthetic methanotrophs'. However, no scalable methane conversion has been demonstrated in E. coli due to the membrane-bound nature of this enzyme and the toxicity of methanol. Pichia pastoris is an efficient methylotroph with a native methanol assimilation pathway and an established host for membrane protein production. This project will express pMMO in the Pichia membrane to enable biological methane conversion. This strain will be further engineered to demonstrate the production of the high value product- 3-hydroxy propionic acid (a precursor of plastics) from methane. This engineered yeast will allow for rapid design-build-test cycles and is well-suited for industrial scale up. Building on a the Fellow's clear potential, with supervision and training at carefully chosen host/cohost, this innovative project will establish synthetic methanotrophy in a standard platform strain for production of valuable products, underpinning a sustainable circular economy.