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.
Highlights
Synthetic biology has expanded our ability to engineer bio-based routes for the production of added-value chemicals, through rational genetic design and metabolic engineering (Choi et al, 2019; Machas et al, 2019; Smanski et al, 2016; Zhang et al, 2019)
Selection from the chemical space of industrially relevant monomers was based on targets that are either found in natural biosynthesis routes, or are biosynthetically accessible based on literature information and prospective bio-retrosynthetic research
We have demonstrated the rapid prototyping capabilities of an automated synthetic biology pipeline for the production of materials monomer targets
Summary
Synthetic biology has expanded our ability to engineer bio-based routes for the production of added-value chemicals, through rational genetic design and metabolic engineering (Choi et al, 2019; Machas et al, 2019; Smanski et al, 2016; Zhang et al, 2019). Metabolic Engineering 60 (2020) 168–182 iterative optimization of production strains (Carbonell et al, 2018a), and machine learning for the translational tuning of biosynthetic pathways (Jervis et al, 2019). Despite such successes in producing natural added-value chemicals, few bio-based alternatives to established chemical products have reached the market, and much effort has to be dedicated toward increasing bioproduction yield (Clomburg et al, 2017; Davy et al, 2017; Wehrs et al, 2019). Further potential benefits from synthetic biology production approaches include rapid access to chemical diversity and the exploitation of enzymatic specificity, which can tackle chemistry that is difficult or not possible through organic synthesis, such as chiral specificity, regioselectivity or functionalization for improved properties (Wagner et al, 2019)
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