Enabling synthetic biology through single cell functional genomics

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.

Grant Number: 5R01AI168993-04
NIH Institute/Center: NIH
Principal Investigator: Michael Burkart