The biosynthetic flexibility associated with the antibiotic natural product erythromycin is both remarkable and utilitarian. Product formation is marked by a modular nature where directing compound variation increasingly spans both the secondary metabolite core scaffold and adorning functionalization patterns. The resulting molecular diversity allows for chemical expansion of the native compound structural space. Accordingly, associated antibiotic bioactivity is expected to expand infectious disease treatment applications. In the enclosed work, new glycosylation patterns spanning the deoxysugars d-forosamine, d-allose, l-noviose, and d-vicenisamine were engineered within the erythromycin biosynthetic system established through an Escherichia coli heterologous production platform. The resulting analogs highlight the expanded flexibility of the erythromycin biosynthetic process. In addition, the new compounds demonstrated bioactivity against multiple Gram-positive tester strains, including erythromycin-resistant Bacillus subtilis, and limited activity against a Gram-negative bacterial target.
Keywords: E. coli; analog; antibiotic; erythromycin; glycosylation; polyketide.
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