Engineering Stimuli-Responsive Protein Complexes Inspired by Anaerobic Fungal Cellulosomes
BR-REMD predictions (green) achieve ≤ 4 Å RMSD when aligned to the structures of benchmark proteins of 65 (left) and 98 (right) residues.
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 in 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.
Scientific Objectives:
- Use modeling-guided FACS screening to develop protein binding domains with switchable binding affinity.
- Use modeling to derive mechanistic hypotheses for switch function and obtain potential design rules.
- Build synthetic protein complexes that change composition in response to environmental inputs.
