APPLICATIONS OF TECHNOLOGY:
- Antibiotic production on an industrial scale
- May lower the production costs of compounds that are only cost-effective to produce using synthetic chemistry
- May increase production titers
Researchers at the Joint BioEnergy Institute (JBEI) have developed an affordable method to produce a diverse arsenal of antibiotics on an industrial scale by using genetically modified host cells in a growth-arrested state.
Antibiotic production by competing technologies has been limited by bacterial cell lysis during the cell-wall-targeting antibiotic production process. Unlike conventional methods, the JBEI invention induces growth arrest in bacterial cells by expressing the HipA toxin to inactivate cell wall biogenesis. This arrested growth maintains bacterial cells’ overall metabolic activity, allowing them to resist antibiotic toxicity and enabling antibiotic production to continue. For example, the Berkeley Lab researchers found that HipA-arrested cells produced mevalonate for nearly one week in the presence of high concentrations (100 mg/L) of the antibiotic ampicillin.
The JBEI technology will be of interest to pharmaceutical companies that employ total organic synthesis to produce antibiotics but are dissatisfied with the limited diversity of antibiotic species to effectively treat bacterial infections as well as the high costs of antibiotic production. The technology could also be used as a research platform for in vivo determination of enzyme activities on toxic substrates to understand the roles of enzymes in antibiotic production pathways.
DEVELOPMENT STAGE: Proven principle.
STATUS: Patent pending. Available for licensing or collaborative research.
REFERENCE NUMBER: 2014-061