Membrane engineering for the improvement of microbial strains for fossil free chemicals and materials production: metabolic engineering strategies driven by molecular dynamics simulations.

Research Project, 2019 – 2021

In the prospect of a bio-based economy the use of biomass as source of hydrocarbons relies on the development of bio-processes to produce renewable chemicals and fuels. In biomass bioconversion processes, microorganisms are often facing tremendous challenges including high concentrations of fermentation inhibiting molecules, such as organic acids and phenolic compounds. Regardless of the product, robust microorganisms are a prerequisite for the feasibility of biomass bioconversion.In the proposed project we will engineer the yeast cell membrane to reduce its permeability to lignocellulose-derived inhibitors, with organic acids and phenolic compounds as case-study, with the final goal of obtaining more robust strains. Molecular dynamics simulations will be used to predict the effect on the physico chemical properties of membranes in which alternative lipids species, known to confer rigidity and reduce permeability are incorporated. These results will guide metabolic engineering strategies to engineer novel strains containing the most promising lipid species. The alternative lipids which will be investigated are 1. longer fatty acid chains in glycerophospholipids; 2. complex sphingolipids from Z. bailii and 3. Cis-unsaturated bacterial lipids. The new strains will be characterised for their tolerance and membrane permeability to organic acids and possibly other inhibitors and this will be correlated to their novel membrane composition.