Exploring the Drug Development Capabilities Hidden in Microbial Genetic Materials
In a groundbreaking discovery, researchers from the University of California, San Diego (UC San Diego) have developed a new genetic platform that aids in the discovery and production of new antibiotics from marine bacteria. This platform, developed at UC San Diego's Scripps Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, could revolutionise the way we approach antibiotic discovery and production.
The synthetic biology technology, which is primarily designed to activate, design, and engineer biosynthetic gene clusters (BGCs) that are typically silent under laboratory conditions, allows researchers to unlock the genetic potential of marine bacteria to produce novel secondary metabolites, including antibiotics, that are otherwise inaccessible using traditional culturing methods.
The researchers used this platform to identify and characterise the taromycin gene cluster in marine bacteria. They then engineered and manipulated this gene cluster to activate the production of a new antibiotic compound, taromycin A, which has been found to be effective in fighting drug-resistant MRSA. The biosynthesis pathway of taromycin A is similar to that of daptomycin, a clinically approved antibiotic.
The study, led by Bradley Moore from Scripps Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, also demonstrated a "plug and play" technique to trigger previously unknown biosynthetic pathways and identify natural product drug candidates. The findings of this study were published in the Proceedings of the National Academy of Sciences.
The ocean is a rich source of new microbial diversity for the discovery of new natural products effective as drugs. By tapping into this largely unexplored secondary metabolite repertoire of marine microbes, the UC San Diego researchers have expanded the diversity of drug candidates, potentially unlocking the drug discovery potential of countless new and mysterious microbes.
The study was supported by grants from the National Institutes of Health. The taromycin antibiotics are now available for licensing. The UC San Diego's Technology Transfer Office has filed patent applications on this process and on the taromycin antibiotics.
This interdisciplinary collaboration between UC San Diego's Scripps Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences combines marine microbiology expertise with advanced pharmaceutical science and synthetic biology to accelerate natural product drug discovery from ocean microbes. This integration helps overcome barriers of culturing difficulty and cryptic gene expression that have historically limited antibiotic discovery from marine bacteria.
The additional contributors to the study include Kazuya Yamanaka, Kirk Reynolds, Roland Kersten, Katherine Ryan, David Gonzalez, and Pieter Dorrestein.
As antibiotic resistance continues to be a critical challenge to public health, and most antibiotics used in human medicine are natural molecules originally isolated from microbes, this discovery could pave the way for new avenues in natural product discoveries and drug development.
[1] Source: Synthetic Biology (2022). [2] Source: Proceedings of the National Academy of Sciences (2022).
- This groundbreaking discovery in the science industry could revolutionize medical-conditions treatment, as the new genetic platform developed at UC San Diego aids in the discovery and production of new antibiotics, like taromycin A, which has been effective in fighting drug-resistant bacteria such as MRSA.
- The health-and-wellness sector may see significant changes due to the financial implications of this discovery, as the taromycin antibiotics, which were developed using this platform, are now available for licensing, potentially leading to new partnerships and investments in the antibiotic production and distribution industry.
- The interdisciplinary collaboration between UC San Diego's Scripps Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences has unlocked the drug discovery potential of countless new and mysterious microbes found in the ocean, potentially leading to a flood of new natural product drug candidates in the future.
