Advanced engineering of C1 metabolism towards methanol-based biotechnology

Background

Pressing issues related to climate change and fossil-fuel dependence requires urgent intervention towards developing biotechnological manufacturing platforms that can efficiently produce value-added commodities in sustainable manner. A key challenge for the development of bio-manufacturing is the need for sustainable, cheap, abundantly available feedstocks for microbial bio-production, which ideally do not compete for arable land and climate. Current bio-manufacturing platforms are mostly based on plant-derived sugars, which exert an undesired pressure on arable land and biodiversity, thereby hindering the realization food security and environmental sustainability. 

Methanol is a promising alternative one-carbon (C1) feedstock, which can be sustainably produced from waste resources or CO2 and renewable hydrogen. Natural microorganisms that can grow on methanol still face various limitations, such as low production rates or inefficient methanol assimilation, for economically feasible bio-manufacturing. Therefore, engineering of an efficient  synthetic methanol assimilation  route, the Reductive Glycine Pathway in the model bioproduction host E. coli system will be a right step towards developing efficient methylotrophy.

Project aims

• Abolish intermediate metabolite toxicity and optimize gene functionality
• Optimize metabolic bottleneck of methanol oxidation and
• Optimize the rGly pathway and the native metabolic network at systems-level in E. coli system towards delivering efficient methylotrophy

Techniques

The project will adopt tools such as MAGE, CRISPR-Cas genome engineering techniques as well as adaptive laboratory evolution to achieve the aims.