Enabling synthetic biology through single cell functional genomics

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Project Summary. In complex ecosystems, microbes use secondary metabolism as a means to communicate within and control their local environment. Some of these products have had profound utility for the treatment of human diseases, particularly infectious disease, where a large percentage of currently prescribed antibiotics are based on or derived from natural products of microbial origin. This program develops, evaluates and implements a new activity-based single cell genomics approach for the discovery of antibiotic candidates from host-associated marine microbes. The research in this collaborative program involves sample collection, single cell genomics, bioinformatics analysis of genomic data with focus on antibiotic producing gene clusters, engineering the most promising clusters into host strains, and flow cytometry-based guided production of these compounds. Using three marine soft-bodied macroorgansims as models (nudibranchs, tunicates and sponges), our team will use a new synthase-selected approach to identify unexplored PKS producing symbiotic microbes, evaluate their genomes for PKS systems and use this genomic data to guide the reconstruction of PKS production in laboratory tractable hosts. The expected results will advance the discovery of novel antibiotic candidates from the microbiomes of marine animals.