SYSTEMS BIOCATALYSIS: A SYNTHETICALLY USEFUL ARTIFICIAL METABOLISM

Systems Biocatalysis is a new approach consisting of organizing enzymes in vitro to generate an artificial metabolism for synthetic purposes. The interconversion of functional groups is the main objective of biocatalysis, and systems organizing a series of enzymes to achieve a multi-step reaction have been reported. The assembly of essentially the same enzymes utilized in Nature to drive the transformation of carbohydrates towards useful synthetic intermediates has been referred to as an artificial metabolism. SysBiocat aims at a similar goal addressing the generalization and organization of group of enzymes (a tool-box) able to perform a series of reactions of general synthetic utility where the feasibility is connected with the obtainment of enzymes of wide substrate specificity or in a rich array of variable common catalytic functions. As a demonstration of this concept, we propose a biochemical like cycle (Asp-cycle) connecting among them an unsaturated carboxylate (fumaric acid), an alpha-amino acid (L-aspartic acid), a keto acid (oxalacetic acid) and the corresponding alpha-hydroxyacid (D- or L-malic acid). The synthetic result will be, in fact, the obtainment from fumarate of either L- or D-malate according to the dehydrogenase used. This series of transformations relies on the catalytic activity of a group of enzymes of known properties. In this view, however, only recently an L-aspartate oxidase has become available for application in biocatalysis. The obtainment of ammonia- and water-lyases, and L-amino acid oxidases of wide substrate specificity, which is a goal hopefully within reach due to the current advancement of protein design will allow to build up and modulate a useful metabolic-like pathway based on functional group interconversion, the goal of SysBiocat.