Arul Mozhy Varman

Metabolic Engineering for Sustainable Biomanufacturing from Complex Substrates

Metabolic engineering has enabled the development of numerous microbial strains for producing fuels and chemicals, yet most rely on simple substrates like glucose and xylose, limiting economic viability. My group engineers microbial systems to convert renewable, low-cost complex feedstocks, such as lignocellulosic biomass, plastics, and CO₂ into value-added chemicals. In doing so, we confront and overcome the compounded challenges that emerge when transitioning from simple sugars to more abundant, yet recalcitrant, substrates. We primarily tackle these challenges by carefully selecting a suitable microbial host and by employing metabolic engineering, synthetic biology, and/or systems biology techniques. The presentation will commence with a discussion on the synthetic biology studies conducted with Bacillus subtilis for utilizing polymeric substrates such as hemicellulose, cellulose, and polyethylene terephthalate towards consolidated bioprocessing. Another significant challenge in biomanufacturing pertains to the toxicity of lignin-derived aromatics to conventionally used microbial cell factories. To overcome this, we employ Corynebacterium glutamicum, a soil microbe naturally capable of growing on diverse aromatic molecules. As a case study, I will delve into the metabolic engineering efforts directed at enhancing the capability of C. glutamicum to produce β-ketoadipate from aromatic monomers. Additionally, while cyanobacteria are attractive microbial hosts for converting CO2 together with organic carbon substrates into several value-added chemicals, their photosynthetic efficiency is relatively low. To address this, my group has been engineering the photosynthetic electron transport chain in a model cyanobacterium, which will be discussed in the final part of the seminar.