A biotransformation approach using microbes as biocatalysts can be an efficient tool for thetargeted modification of existing antibiotic chemical scaffolds to create previouslyuncharacterized therapeutic agents. By employing a recombinant Streptomyces venezuelaestrain as a microbial catalyst, a reduced macrolide, 10,11-dihydrorosamicin, was created fromrosamicin macrolide. Its chemical structure was spectroscopically elucidated, and the newrosamicin analog showed 2-4-fold higher antibacterial activity against two strains ofmethicillin-resistant Staphylococcus aureus compared with its parent rosamicin. This kind ofbiocatalytic approach is able to expand existing antibiotic entities and can also provide morediverse therapeutic resources.