Anaerobic gut fungi produce cellulosomes for synergistic hydrolysis of lignocellulose. Complex assembly is mediated by dockerin-fused catalytic enzymes, which can bind to a non-catalytic scaffold that is anchored to the cell membrane.
Most metabolic pathways are built from individual enzyme-substrate reactions that take place in tandem. Since thousands of enzyme-catalyzed reactions occur simultaneously within cells, nature evolved clever ways to enhance reaction rates by restricting protein mobility. A key example is the enzyme scaffolding found anaerobic microbes. Cellulosomes tether enzymes together through modular protein motifs that drive breakdown of plant matter into sugar, which can be fermented into commodity chemicals. Here, we will engineer synthetic enzyme complexes inspired by the modular interacting domains we recently identified from anaerobic fungi, which sense-and-respond to their external environment for applications in the production of value-added chemicals from waste materials.