Ancestral Sequence Reconstruction leads to Robust Enzymes
ROBOX has been highly focussed on developing commercial biocatalysts that requires robust enzymes that can withstand elevated temperatures and long incubations as well as stability to organic substrates and solvents. In an interesting approach to this problem Elizabeth Gillam and coworkers have used ancestral reconstruction of pre-Cambrian enzymes and they are then often much more thermostable than extant forms that complements ROBOX work.
In the latest study CYP450 ancestral enzymes that withstand ~30 °C higher temperatures and ≥100 times longer incubations than their extant forms is demonstrated on animal cytochrome P450s.
The vertebrate CYP3 P450 ancestor enhanced thermal and solvent tolerance compared with the human drug metabolizing CYP3A4 and comparable activity towards a similarly broad range of substrates.