Automated engineering of synthetic metabolic pathways for efficient association to reaction rules.biomanufacturing

Abstract Metabolic engineering involves the engineering and optimization of processes from single-cell to fermentation in order to increase production of valuable chemicals for health, food, energy, materials and others. A systems approach to metabolic engineering has gained traction in recent years thanks to advances in strain engineering, leading to an accelerated scaling from rapid prototyping to industrial production. Metabolic engineering is nowadays on track towards a truly manufacturing technology, with reduced times from conception to production enabled by automated protocols for DNA assembly of metabolic pathways in engineered producer strains. In this review, we discuss how the success of the metabolic engineering pipeline often relies on retrobiosynthetic protocols able to identify promising production routes and dynamic regulation strategies through automated biodesign algorithms, which are subsequently assembled as embedded integrated genetic circuits in the host strain. Those approaches are orchestrated by an experimental design strategy that provides optimal scheduling planning of the DNA assembly, rapid prototyping and, ultimately, brings forward an accelerated Design-Build-Test-Learn cycle and the overall optimization of the biomanufacturing process. Achieving such a vision will address the increasingly compelling demand in our society for delivering valuable biomolecules in an affordable, inclusive and sustainable bioeconomy.