Designing thermophilic, synthetic microbial communities for consolidated bioprocessing

Lignocellulose-derived fuels and chemicals are vital to breaking the world's dependence on fossil fuels. Though plant biomass is notoriously resistant to deconstruction, lignocellulolytic thermophiles are especially adept at degrading its constituent polysaccharides into mono- and oligo-saccharides for catabolism. And many thermophiles, whether lignocellulolytic or not, can be engineered to ferment lignocellulose-derived sugars into valuable fuels and chemicals as part of consolidated bioprocesses. Although the past twenty years have seen major advances in the genetic and metabolic engineering of individual thermophiles, the strategy of co-culturing thermophilic strains as part of synthetic communities has not been well established. Synthetic communities unlock synergistic interactions that outperform monocultures, thereby enhancing product titers, rates, and yields. While limited genetic tools once hindered the development of synthetic thermophilic communities, recent advances now offer robust systems for engineering these industrially relevant organisms. Here, we propose that this expanded genetic malleability enables engineering of 1) transport specialization to reduce substrate competition between strains and 2) division of labor strategies whereby one strain focuses on lignocellulose deconstruction while another strain dedicates metabolic burden for product synthesis. We draw on examples of engineered thermophiles like Clostridium thermocellum, Thermoanaerobacter saccharolyticum, and Anaerocellum bescii to illustrate how these mechanisms have been applied in thermophilic co-cultures. In brief, this perspective outlines design principles to construct effective thermophilic communities for lignocellulose bioprocessing.