[1S01m] 10. ASPIRE - Part 1

11:36 AM - 11:48 AM JST(2:36 AM - 2:48 AM UTC)

[1ASPR-05] Advancing the Biomanufacturing Technology Stack at the London Biofoundry.

○Marko Storch¹ (1. Imperial College London (UK))

Keywords:

Biofoundry,Pathway engineering,Strain engineering,Bioprocess engineering,Translational research

Biofoundries are cutting-edge synthetic biology laboratories where software development, innovative instrumentation and lab automation are combined to advance the study and engineering of molecules and cells for the bioeconomy. Within highly collaborative communities like the Global Center for Biofoundry Applications and the Global Biofoundry Alliance we are researching novel methods, workflows and research capabilities including metrics and standards for productive biomanufacturing across institutions. At the London Biofoundry we are developing an integrated technology stack advancing the biomanufacturing capabilities in close collaboration with our ecosystem focused on bacteria and yeast systems. Starting with in-house DNA synthesis and gene assembly, we are developing rapid Design-Build-Test-Learn cycles for the improvement of enzymes, metabolic pathways and production strains. We implemented cost-effective DNA synthesis and assembly workflows on our automation platforms leveraging acoustic and tip-based liquid handling to produce large arrays of DNA constructs and libraries for metabolic pathway engineering. Cell-free protein expression systems allow us to study genetic element and enzyme functions in miniaturised high-throughput formats and guide the refinement of pathway features and architectures before implementing them in cell factories. Such a fully integrated workflow with automated transformation into production strains allows for rapid exploration of the pathway design space through. For high-throughput strain characterisation we develop assays across plate reader, high performance liquid chromatography and mass spectrometry platforms. Addressing a major bottleneck in the characterisation pipeline, we started developing high-throughput assays leveraging Acoustic Ejection Mass Spectrometry reducing sampling rates to seconds. This improvement in speed by an order of magnitude unlocks ambitious kinetics and high-throughput screening studies, further improving the enzyme and strain characterisation platform. Selected strains are then developed along a pre-scale-up pathway taking the culture volumes from 100uL to 20L with an integrated data strategy across bioreactor platforms. Finally, in-house short and long-read sequencing technologies allow for the rapid confirmation of DNA and strain engineering steps as well as the study of genetic stability during production conditions.