The microbial production of fuels and chemicals from renewable feedstock is a grand challenge for synthetic biology. To date, no microbial chassis has been developed for lignin utilization despite the success of similar approaches with sugars. Although lignin is an abundant, energy-dense polymer that makes up ~30% of plant biomass, it is recalcitrant to degradation. In contrast to cellulose, lignin cannot be readily cleaved into homogenous subunits because it is composed of diverse phenyl-propanoid compounds connected by non-uniform chemical linkages. This complexity makes the targeted degradation of lignin a daunting challenge and results in the dramatic, wasteful underutilization of lignin as a feedstock. In nature, the complete degradation of lignin involves microbial consortia. Although no single organism encodes all the enzymes needed for efficient lignin catabolism, natural metabolic pathways provide a rich catalytic toolbox. We have assembled a multi-disciplinary team to engineer the first lignin-degrading chassis using a bacterium, Acinetobacter baylyi ADP1. Utilising the unique genetic system of ADP1, we will evolve efficient catabolic devices to expand the degradation of mixtures of lignin-derived aromatic compounds. To complement the microbial genetics, a combination of GC-MS metabalomic and metabolic flux methods will be used to quantify intermediates in the lignin catabolic pathway and in silico metabolic modelling will allow us to target enzymatic bottlenecks and improve lignin catabolism. These specific enzymes will enter our structural biology and protein engineering platform, where we will fully characterise and adapt them with the goal of constructing superior enzyme 'machines' for the efficient conversion of lignin to desired products. These engineered enzymes will then be incorporated back into ADP1 and multiple iterative cycles will allow us to continually improve the efficiency of the system.
|Effective start/end date||1/10/16 → 30/09/19|
- Biotechnology and Biological Sciences Research Council: £390,930.78
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