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Exploring the Ocean

The ocean, covering 70 percent of Earth's surface, is a rich source of novel microbial diversity for the discovery of new natural products effective as drugs for treating infectious diseases. Our unique geographic and academic environment brings together the world class scientists of UC San Diego Scripps Institution of Oceanography (SIO), the School of Medicine (SOM), and Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) into multidisciplinary teams to successfully exploit this vast untapped natural resource for antibiotic drug discovery.


Center for Marine Biotechnology and Biomedicine

Marine natural product antibiotic discovery is a joint effort of scientists of CHARM and the Center for Marine Biotechnology and Biomedicine (CMBB), a campuswide UC San Diego research division dedicated to the exploration of the novel and diverse resources of the ocean.  CMBB scientists investigate a wide range of biotechnologies, from the genomic and chemical analysis of deep-sea marine microbes, to the genetic engineering of viable marine animals as new models for understanding of host-pathogen interactions.

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A Sunken Treasure of Novel Antibiotic Discovery

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UC San Diego investigators have explored ocean habitats worldwide, from the deepest oceans, to tropical lagoons, to waters just off Scripps Pier here in La Jolla.  New cultivation techniques have allowed recovery of several dozen novel families and genera of microbes including Actinomycetes, Streptomycetes, fungi and cyanobacteria, living in ocean sediments or as commensals on marine animals such as corals and sponges. The application of genome sequencing, high throughput MS-based metabolomics and recombinant technology to the natural product discovery process has allowed us to interrogate and manipulate biosynthetic processes in order to expand the biosynthetic capabilities of microbes to yield new chemical entities for biological evaluation.


Opportunities and Challenges

The goal of our collaborative programs are to emphasizes the discovery of new molecules with unprecedented chemical structures and clinically relevant pharmacological activities. We are striving to meet the technological challenges of accessing uncharted marine environments, propagating microbes long though unculturable, and genetically accessing and manipulating natural product biosynthetic operons to generate new chemical diversity.  Our screens are also expanding beyond classical antibiotic testing to screens for virulence factor inhibitors and immune boosters that can aid in the treatment of the leading contemporary drug-resistant infectious threats.

 

Awakening Hidden Antibiotics

CHARM and CMBB investigators identified and cloned the streptophenazine biosynthetic pathway (spx) from a marine Streptomyces bacterium. Refactoring and controlled expression of the pathway in E. coli led led to tremendous chemical diversity (112 different compounds).  In particular, streptophenazines with an N-formylglycine moeity showed potent antibiotic activity.

Read article at Cell Chemical Biology