A heterologous expression toolkit for large-scale production of novel antimicrobials from diverse microbes Completed Project uri icon

description

  • New antimicrobials (antibiotics, antifungals and fungicides) are an urgent need. Each year ?1.2Mn people die from drug-resistant infections and fungal crop diseases resulting in yield losses of up to 50% for major crops. For new antimicrobials to work against this backdrop of resistance, they must be chemically different from existing solutions, meaning they must be discovered from previously unexplored sources or using novel chemical techniques. 80% of clinically-used antibiotics and many agricultural fungicides derive from the 1% of microbes which can readily be cultured in the laboratory. The remaining 99% unculturable microbes are life's biggest unexplored bioresource. If cultured, these organisms can be screened for a wealth of new antimicrobial compounds. At Bactobio, we use breakthrough techniques in next-generation sequencing, engineering biology and machine learning to domesticate previously unculturable microbes and screen them for new solutions. Our bioactivity-guided approach is unique and differentiated from major competitors, accelerating our search for new bioactive molecules. Generating sufficient chemical material from novel species is a significant bottleneck to our discovery pipeline. Because our microbes are often slow- or difficult-to-culture, they do not produce enough of our new antimicrobial compounds for the chemical testing required to take them to market. In this project, we will generate and apply a toolkit of microbial producer species for robust biomanufacturing of novel compounds from our genetically diverse microbes. These microbial chassis will be programmed to produce valuable new chemical solutions, starting with 2-5 novel biologically-derived fungicide compounds with activity against the UK's biggest wheat pathogen: _Zymoseptoria tritici_.

date/time interval

  • August 31, 2023 - November 30, 2024