Enzymes are important biological components for SynBio: they catalyse the chemical reactions that underpin many SynBio applications in industrial biotechnology. Advances in metabolic engineering, particularly in predictive metabolic modelling and genome editing, now allow us to use enzymes in combinations that do not occur in nature and generate metabolic pathways that allow production of wholly novel chemicals. As impressive as recent advances in metabolic engineering are, we are still constrained to the use of those biochemical reactions that have already been characterised. Ideally, we would be able to design a new protein, even where we do not currently have enzymes that are known to catalyse all of the individual steps.
Biology has been doing chemistry for billions of years and over that time it has built an enormous repertoire of highly efficient enzymes through the ‘trial-and-error’ process of natural evolution. However, biology has ‘focused’ on a narrow range of chemical reactions and applications. As a consequence, there are chemical steps that, while desirable for novel metabolic pathways, are not catalysed by known enzymes. To expand upon the natural range of enzyme biochemistry, we have used structure-based and computational techniques to move beyond the trial and error approach that biology has employed and employ engineering principles to design new enzyme applications.