Implementation of a "Design-Build-Test-Learn" cycle for the rational construction of microbial platforms for muconic acid production

Abstract

The transition from the fossil-based economy towards a sustainable bioeconomy based on renewable resources plays a central role in mitigating global emissions of greenhouse gases and environmental pollution. In this context, the use of microorganisms as platforms capable of efficiently converting renewable raw materials into various biochemicals, biofuels, and biomaterials has been considered a promising alternative for this transition. With this motivation, the present proposal aims to develop a microbial platform for cis,cis-muconic acid production. This chemical intermediate that has been attracting interest for its application as an intermediate for the synthesis of various bioplastics, mainly terephthalic polyethylene (PET) and nylon-6.6, which are indispensable for a modern society, and which are traditionally obtained by petrochemical routes. Therefore, we intend to implement an iterative cycle of "Design-Build-Test-Learn" associated with a multidisciplinary approach based on systems metabolic engineering tools, including genome-scale metabolic models, screening potential enzymes from metagenomic libraries, advanced techniques of genetic editing and integration of metabolomic and 13C-Fluxomic, in order to accelerate the construction of Escherichia coli strains to overproduce muconic acid. This project has a great potential to contribute to developing an efficient bioprocess for a bioproduction of muconic acid from abundant and renewable substrates, such as glucose, available in the integration with sugarcane biorefineries, and glycerol, an abundant residue of the biodiesel industry. (AU)