Rapid prototyping of microbial production strains for the biomanufacture of potential materials monomers
Christopher Robinson, Pablo Carbonell, Adrian J. Jervis, Cunyu Yan, Katherine A. Hollywood, Mark S. Dunstan, Andrew Currin, Neil Swainston, Reynard Spiess, Sandra Taylor, Paul Mulherin, Steven J. Parker, William Rowe, Nicholas E. Matthews, Kirk J. Malone, Rosalind Le Feuvre, Philip Shapira, Perdita E. Barran, Nicholas J. Turner, Jason Micklefield, Rainer Breitling, Eriko Takano, Nigel S. Scrutton
Abstract
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.