Evolution-based model for designing chorismate mutase enzymes
July 28th, 2020
The rational design of enzymes is an important goal for both fundamental and practical reasons. Here, we describe a process to learn the constraints for specifying proteins purely from evolutionary sequence data, design and build libraries of synthetic genes, and test them for activity in vivo using a quantitative complementation assay. For chorismate mutase, a key enzyme in the biosynthesis of aromatic amino acids, we demonstrate the design of natural-like catalytic function with substantial sequence diversity. Further optimization focuses the generative model towards function in a specific genomic context. The data show that sequence-based statistical models suffice to specify proteins and provide access to an enormous space of functional sequences. This result provides a foundation for a general process for evolution-based design of artificial proteins.
More information:
science.sciencemag.org/content/369/6502/440
DOI: 10.1126/science.aba3304
Rémi Monasson - Simona Cocco
Laboratoire de Physique de L’Ecole normale supérieure (LPENS, ENS Paris/CNRS/Sorbonne Université/Université de Paris)
Provided by The Physics Laboratory of the Ecole Normale Supérieure