CAREER: Engineering robust and stable synthetic microbial consortia for targeted waste-to-platform chemical conversion

Conversion of low-value waste into valuable products using microbes can help strengthen the domestic supply of important chemicals. One such product is caproate, a medium-chain carboxylic acid used in fuels, animal feed, cosmetics, and other applications. However, making caproate from waste remains difficult. Challenges include low yields, poor selectivity, and unwanted byproducts. Synthetic microbial consortia, which are groups of microbes selected for specific waste types and end products, offer a promising solution. However, effective strategies are needed to make these systems stable and efficient. This CAREER project will develop engineering and modeling tools to design microbial consortia that efficiently convert dairy and brewery waste into caproate. The project will also train students at multiple academic levels, increase public awareness about waste upcycling, and strengthen partnerships among universities, industry, and local communities. Harnessing microbial consortia for waste valorization presents a considerable opportunity to shift from traditional waste treatment towards resource recovery. Monocultures often lack the enzymatic breadth for multi-step waste conversion, while mixed cultures suffer from poor selectivity and byproduct formation. Synthetic microbial consortia offer a modular alternative to conventional mixed culture or pure culture for biomanufacturing. Despite their high potential, the application of such synthetic microbial consortia is limited by challenges in selecting optimal microbial partners that best metabolizes complex waste from a wide pool of microbes, predicting interspecies metabolic interactions that shape consortia’s function, and maintaining long-term functionality and stability in non-sterile waste. To address these challenges, this CAREER project will engineer high-yielding synthetic microbial consortia for biomanufacturing of caproate from waste through three integrated research objectives: (1) develop a high-throughput, community-scale metabolic modeling framework to simulate interspecies interactions and guide selection of highest caproate producing synthetic microbial consortia for experimental validation; (2) engineer hydrogel encapsulation to enhance retention, stability, and functionality of synthetic consortia by fine-tuning composition and density of the polymer and cross-linker; and (3) evaluate the productivity and competitive advantage of encapsulated consortia for bioconversion of organic waste streams under environmentally relevant conditions. These research efforts will be closely integrated with a comprehensive education plan that includes 1) project-based workshop on engineering design and programming for high school students; 2) creation of an educational video highlighting student-led research and partnerships with local industries to foster public engagement and scientific literacy in waste upcycling; and 3) integration of innovative modules into undergraduate and graduate curricula. Together, these efforts will advance environmental biotechnology and develop skilled workforce to enable scalable and resilient biomanufacturing from waste. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2541327 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Shilva Shrestha | Institution: Johns Hopkins University, BALTIMORE, MD | Award Amount: $550,000 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2541327 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2541327.html