Scientists in the UK have demonstrated that bottromycin (an antibiotic that works against MRSA) is biosynthesised from a larger precursor ribosomal peptide. This was proposed following a genome mining analysis of Streptomyces scabies and confirmed by a series of gene deletion experiments. The work also identifies S. scabies as a previously unknown producer of bottromycin. An almost identical gene cluster was also identified in S. bottropensis, an established bottromycin producer. Bottromycin is the first ribosomal peptide natural product that derives from the N-terminus of a larger prepeptide and the first terrestrial peptide to be directly ethylated at beta-positions.
Bottromycin is active in vitro but unstable in vivo so if scientists can engineer its biosynthesis to make unnatural analogues they might be able to make good new antibiotics. By identifying this pathway the team should facilitate the generation of a library of bottromycin-like antibiotics.
Link to journal article
Identification and characterisation of the gene cluster for the anti-MRSA antibiotic bottromycin: Expanding the biosynthetic diversity of ribosomal peptides
W J K Crone, F J Leeper and A W Truman
Chem. Sci., 2012, DOI: 10.1039/c2sc21190d