Developing a synthetic biology platform for pharmaceutical biomanufacturing

Enzyme biocatalysts promise to reduce carbon emissions and improve supply chain resilience of the $200 billion pharmaceutical manufacturing industry that emits 52,000,000 tons of CO2 per year. However, the speed of engineering fit-for-purpose enzymes is bottlenecked by slow chromatographic screening, which requires 1-5 minutes to measure each sample. To address this issue, we propose to develop a platform for the generation of custom allosteric transcription factors (aTFs) that enable enzyme screening up to 1,000,000 times faster than chromatography via fluorescence-activated cell sorting. A panel of highly evolvable aTFs will be established and screened against pharmaceuticals to generate a ‘specificity map’ of aTF-drug interactions. Using this data, one aTF will then be engineered to stereospecifically recognize R-tetrahydropapaverine, an intermediate used in the production of the FDA-approved drug cisatracurium whose manufacture could be streamlined via biocatalysis. Completion of this pilot study will assess the potential of custom aTFs for ultra high-throughput screening of enzymes for the sustainable biomanufacturing of pharmaceuticals.