Nature's directed evolution coupled with high-throughput sequencing
Summary
Prospect Bio was predicated on building a rapid and inexpensive alternative to traditional analytical methods for chemical identification and quantification. To this end, the company engineered bacteria to respond with high specificity to target compounds, productizing the success of previous academic work that led to lignin by-product biosensors.
To exploit nature's ability to fit elegant solutions to challenging problems, we used microbial DNA found in diverse environments (oil fields, highly salinated waters, deep ocean layers) as starting points for genetic diversity. For microbial life to sustain life in these challenging environments they must adapt their cellular machinery to cope with the otherwise deadly conditions. The adapted genes were inserted into Prospect Bio's expression vector which contained a fluorescent reporter gene downstream of the microbial DNA. This gene construct would generate a measurable fluorescent signal if the microbial DNA was expressed. The complete gene construct was inserted into E.coli, the company's host organism of choice.
To rapidly assay the metagenomic library, we optimized the E.coli growth and expression timing for 96- and 384-well plates. Parallelizing biosensor discovery through our plate based approach provided scalability that traditional analytical methods could not offer.
Industry Partnerships
Reliance Industries: Prospect Bio developed an isoprene sensor for use with Reliance's bioreactors to produce petroleum product precursors.
Ginkgo Bioworks: Gingko Bioworks asked for three small molecule biosensors, two of which were successfully delivered. The partner project led to seed funding of nearly $3M.
Constellation Brands: To combat wine fraud, Constellation Brands explored the possibility to rapidly discern wine varietals and blends of varietals by biosensor fingerprinting. Measuring heterogenous mixtures proved challenging but was eventually made possible through panels of biosenors coupled with ML-based classification.
Progenity (now Biora Therapeutics): In an attempt to develop a pre-clinical diagnostic for pre-eclampsia, Progenity partnered with Prospect Bio to identify pre-eclampsia from pre-natal urine samples. Adapting the biosenor panel approach to urine analysis, we developed methods to identify at-risk patients. Sequence analysis of the panel's constituent biosenors provided indication to which small molecules elicited responses. These small molecules provided an opportunity to develop traditional diagnostics.