Systems biocatalysis, cell free artificial metabolism

corresponding

PAOLA D’ARRIGO1,2, STEFANO SERVI2*
*Corresponding author
1. Department of Chemistry, Materials and Chemical Engineering “G. Natta”,
Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy
2. The Protein Factory, Politecnico di Milano and Università degli Studi dell’Insubria,
Via Mancinelli 7, 20131 Milano, Italy

Abstract

Systems biocatalysis is an approach consisting of organizing enzymes in vitro to generate an artificial metabolism for synthetic purposes following the identification of a reaction sequence catalysed by specific enzymes, construction of a controllable metabolic pathway and process intensification for the effective production of the products. It is a complement to metabolic engineering. Examples in the production of small molecules from renewables, reaction sequences involving serial functional group transformation, the construction of metabolic like cycles will be discussed.


INTRODUCTION

The production of small or large molecules from renewable resources is central in modern chemical industry. Enzymatic catalysts are increasingly involved in processes related to the transformation / production of bio-derived materials. The evolution of the use of biological systems as producing tools can be summarised as involving the following techniques:

Extraction of natural products from plants or from natural microbial biomasses grown for the scope

Substrate modification catalysed by resting or growing cells as source of enzymatic catalysts (whole cells biotransformations)

Isolated (purified ) enzymes as biocatalysts for the selective transformation of a given substrate

Modification of the metabolism of a specific microorganism to improve the production of the required metabolite previously obtained as in point 1).

All four methodologies have industrial applications but the design of microorganisms with a modified metabolic pathway finalised at the production of end-products or the equivalent in vitro artificial metabolism are the subject of increasing efforts. Recently several enzymatic catalysts ...