PremethylenomycinC lactone is a natural product with potent antibiotic activity, effective against bacteria such as methicillin-resistant (MRSA) and vancomycin-resistant (VRE).
Discovery The compound was identified unintentionally during investigations of the biosynthetic gene cluster in , a bacterium found in soil. Genetic blockade of a specific enzymatic step by deletion of the mmyEgene led to the accumulation and isolation of previously intermediates, including C and its lactone derivative.
In the biosynthetic pathway that produces A, C lactone is an early . Hydrolysis of the lactonering followed by dehydration yields C, which is subsequently oxidized to form the epoxide A.
Bioactivity Compared with methylenomycinA and C, C and its lactone precursor exhibit activity oneto two ordersof magnitude greater against a range of bacteria, including -resistant isolates of and . They also do not have the -γ- of A andC, implying they have a different modeof action. These properties highlight the compounds in this metabolic series as potential lead structures for developing new antibiotics to combat resistance.
Chemistry Beyond its natural production, C lactone can be prepared synthetically via a , phosphine-mediated reaction, providing a route for larger‑scale preparation and structure–activity relationship studies.
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