Patent Evaluation: Genetically Engineered Microbes that Produce 6-deoxyerythromycin

Summary

Novelty: Novel 6-deoxyerythromycin derivatives potentially useful as antibacterial agents are disclosed. The compounds are claimed to possess improved acid stability and are microbially produced. Genetically modified microorganisms which produce these compounds are also disclosed.

Biology: In an in vivo mouse protection assay (Staph. aureus), 90.8 mg/kg po produces 50% survival compared with 119.6 mg/kg for erythromycin A. Against Strep. pneumoniae and Strep. pyogenes, 24.9 and 32.4 mg/kg produce 50% survival, respectively (compared with 24.8 and 54.5 mg/kg for erythromycin A). In vitro data are provided (MIC₅₀=0.12–12.8 μg/ml compared with 0.015–32 μg/ml for erythromycin A and 0.03–32 μg/ml for erythromycin B).

Chemistry: 3-α-Mycarosyl-6-deoxyerythronolide B is specifically claimed.

Structure: