Oxygen limitation is a major obstacle in antibiotic fermentations that utilize the aerobic bacteria Streptomyces. Current methods to increase oxygen transfer to Streptomyces include improved bioreactor design and modified culture media. A novel approach to the problem of oxygen transfer is the development of strains that can obtain oxygen from the medium more efficiently. The current proposal is directed towards the development of a genetically modified strain that expresses a bacterial hemoglobin-like protein. This protein was originally discovered in the aerobic bacteria Vitreoscilla, and apparently enables the cells to survive in a oxygen-poor environment. When Vitreoscilla hemoglobin was expressed in the bacteria Escherichia coli, the recombinant cells demonstrated higher growth and respiration rates, and grew to higher cell densities. The gene encoding this protein will be introduced into Streptomyces coelicolor, which produces the antibiotic actinorhodin. The recombinant cells will then be tested for their growth and respiratory properties, and actinorhodin production. The demonstration of enhanced growth, respiration, and/or actinorhodin yields in this system will have broad implications not only for antibiotic fermentations but for any bioprocess system that involves aerobic cell culture.
