Eliciting Production of Bioactive Molecules via Co-Cultivation of Microbes

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The structure of Rhodostreptomycin A (left column; top depiction includes NMR data) and Rhodostreptomycin B (right column; top depiction includes NMR data).
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Inventors
Professor Anthony Sinskey
Department of Biology, MIT
Kazuhiko Kurosawa
Department of Biology, MIT
Philip Lessard
Department of Biology
Managed By
Jon Gilbert
MIT Technology Licensing Officer
Patent Protection

Bioactive Molecules from Co-Cultivation of Microbes

US Patent 8,314,071

Applications

Bioactive molecules produced by the co-cultivation of microbes have the potential to be used as antibiotics. A method for the production and purification of new bioactive molecules would open the door to potentially unlimited varieties of antibiotics. 

Problem Addressed

Microbiologists have long worried about the growing resistance of bacteria and other microbes to existing antibacterial agents due to the overuse of antibiotics. As a result, there is an on-going need to develop new antibiotics to counteract this evolution of resistance. 

Technology

This invention involves the co-incubation of Rhodococcus fascians with Streptomyces padanus to produce two new isomeric antibiotics, coined rhodostreptomycin A and B. The Rhodococcus fascians strain that developed the ability to produce these two new antibiotics, 307CO, was able to eliminate Streptomyces from its culture, presumably by the toxicity of rhodostreptomycin A and B. The inventors have hypothesized that Rhodococcus fascians gained the ability to produce rhodostreptomycin through a lateral gene transfer from its co-cultured Streptomyces. Genomic analysis revealed that 307CO harbored a long strand of DNA derived from Streptomyces. Furthermore, rhodostreptomycin A and B production correlated with the presence of Streptomyces-derived DNA in Rhodococcus. Rhodostreptomycin was purified by fractionation, cation exchange, and reverse-phased HLPC. NMR analysis was used to reveal the chemical formula and hydrocarbon structure of rhodostreptomycin A and B and verify their novelty. Rhodostreptomycin A and B were not shown to have any activity against eukaryotes when applied to S. Cerevisiae or human leukemia (HL-60). 

Advantages

  • Method for the production of new antibiotics
  • Production of two new antibiotics, rhodostreptomycin A and B, by bacterial strain Rhodococcus fascians 307CO 
  • Eukaryotes unaffected by rhodostreptomycin A and B