Preparation of erythromycin analogs having functional groups at C-15

Area of Science:

• Synthetic biology
• Medicinal chemistry
• Microbiology

Background:

• Erythromycin analogs are crucial antibacterial macrolides.
• Modifications at the 15-position can alter physicochemical properties.
• Chemocynthesis offers a route to novel antibiotic structures.

Purpose of the Study:

• To prepare novel erythromycin analogs with unique functional groups at the 15-position using chemocynthesis.
• To explore the potential of these analogs as antibacterial agents with altered properties.
• To enable selective derivatization of these new macrolide structures.

Main Methods:

• Utilized diketide thioester feeding in genetically engineered Streptomyces coelicolor.
• Produced 15-fluoro, 15-chloro, and 15-azido analogs of 6-deoxyerythronolide B.
• Employed bioconversion with a genetically engineered Saccharopolyspora erythraea mutant.

Main Results:

• Successfully synthesized erythromycin analogs with 15-fluoro, 15-chloro, and 15-azido groups.
• Produced 15-fluoroerythromycin A and 15-azidoerythromycin A via bioconversion.
• The new analogs possess unique physicochemical properties and functional handles.

Conclusions:

• Chemocynthesis is effective for generating novel erythromycin analogs with tailored 15-position functionalities.
• These modified macrolides represent promising candidates for new antibacterial therapies.
• The introduced functional groups facilitate further chemical modification and drug development.