Rapid prototyping of microbial production strains for the biomanufacture of potential materials monomers

Bio-based production of industrial chemicals using synthetic biology can provide alternative green routes from renewable resources, allowing for cleaner production processes. To efficiently produce chemicals on-demand through microbial strain engineering, biomanufacturing foundries have developed automated pipelines that are largely compound agnostic in their time to delivery. Here we benchmark the capabilities of a biomanufacturing pipeline to enable rapid prototyping of microbial cell factories for the production of chemically diverse industrially relevant material building blocks. Over 85 days the pipeline was able to produce 17 potential material monomers and key intermediates by combining 160 genetic parts into 115 unique biosynthetic pathways. To explore the scale-up potential of our prototype production strains, we optimized the enantioselective production of mandelic acid and hydroxymandelic acid, achieving gram-scale production in fed-batch fermenters. The high success rate in the rapid design and prototyping of microbially-produced material building blocks reveals the potential role of biofoundries in leading the transition to sustainable materials production.
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Highlights • An automated biomanufacturing pipeline is benchmarked for the production of material monomers. • Over 85 days, 160 genes were screened for activity, assembled into 115 unique pathways and tested for in vivo production. • E. coli production strains were successfully constructed to produce 17 target compounds at competitive titers. • Scale-up potential is demonstrated through enantioselective production of mandelic acid targets at gram-scale in bioreactors. • The high success rate demonstrates the capabilities of biofoundries to rapidly prototype microbial production strains.