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Principal Investigator: Michael D. Burkart
Organization: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Fiscal Year: 2024
Award: $434,671
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <Anabolism><Animals><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Bio-Informatics><Bioinformatics><Biology><Carrier Proteins><Cell Body><Cells><Chemicals><Color><Communicable Diseases><Communication><Complex><Data><Dehydratases><Development><ESKAPE><ESKAPE pathogens><Ecologic Systems><Ecological Systems><Ecosystem><Engineering><Ensure><Environment><Fatty Acids><Finding natural products><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Functional Metagenomics><Gene Cluster><Genome><Genomic approach><Genomics><Goals><Hybrids><Hydrases><Hydro-Lyases><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Intermediary Metabolism><Label><Laboratories><Metabolic><Metabolic Processes><Metabolism><Metagenomics><Methodology><Methods><Microbe><Microbial Bioactive Compound><Microbial Secondary Metabolite><Microbial natural product><Microbial-Derived Compound><Miscellaneous Antibiotic><Modeling><Molecular Probes><Natural Products><Natural Source><Natural product discovery><Needles><Organism><PKS enzyme><Peptides><Planets><Play><Porifera><Preparation><Production><Research><Role><Sorting><Source><Sponges><System><Transport Protein Gene><Transport Proteins><Transporter Protein><Tunicata><Tunicates><Urochordata><Urochordates><biosynthesis><derived from natural product><developmental><flow cytophotometry><functional genomics><genetic make-up><genetic makeup><genome database><genomic data><genomic data-set><genomic dataset><genomic effort><genomic strategy><human disease><innovate><innovation><innovative><insight><living system><marine><marine environment><marine natural product><microbe pathogen><microbial><microbial pathogen><microbiome><natural product derivative><natural product derived compound><naturally occurring product><new approaches><novel><novel approaches><novel strategies><novel strategy><nudibranch><pathogenic microbe><polyketide synthase><polyketides><preparations><programs><reconstruction><sample collection><sea squirt><single cell genomics><social role><specimen collection><synthetic biology>