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

Christopher Robinson, Pablo Carbonell, Adrian Jervis, Cunyu Yan, Katherine Hollywood, Andrew Currin, Neil Swainston, Reynard Speiss, Sandra Taylor, Paul Mulherin, Steven Parker, William Rowe, Nick Matthews, Kirk Malone, Rosalind Le Feuvre, Philip Shapira, Perdita Barran, Nicholas Turner, Jason Micklefield, Rainer BreitlingEriko Takano, Nigel Scrutton

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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.
Original languageEnglish
JournalMetabolic Engineering
Early online date23 Apr 2020
DOIs
Publication statusPublished - 1 Jul 2020

Keywords

  • synthetic biology
  • biofoundry
  • biomanufacturing
  • industrial biotechnology
  • mandelic acid
  • hydroxymandelic acid

Research Beacons, Institutes and Platforms

  • Manchester Institute of Biotechnology

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  • Biochemical and Biophysical Sciences Technology Platform

    Heyes, D. (Senior Technical Specialist), Boothman, C. (Senior Technical Specialist), Cliffe, L. (Technical Specialist), Dunstan, M. (Senior Technical Specialist), Golovanova, M. (Senior Technician), Hoeven, R. (Technical Specialist), Lopez Perez, R. (Senior Technician), Sakuma, M. (Senior Technician), Tait, S. (Senior Technician) & Tilakaratna, V. (Senior Technician)

    FSE Research

    Facility/equipment: Platform

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