Now showing 1 - 4 of 4
  • Publication
    Production of the Novel Lipopeptide Antibiotic Trifluorosurfactin via Precursor-Directed Biosynthesis
    Incorporation of fluorine into antibiotics can moderate their biological activity, lipophilicity and metabolic stability. The introduction of fluorine into an antimicrobial lipopeptide produced by Bacillus sp. CS93 via precursor-directed biosynthesis is described. The lipopeptide surfactin is synthesised non-ribosomally by various Bacillus species and is known for its biological activity. Administering 4,4,4-trifluoro-dl-valine to cultures of Bacillus sp. CS93 results in the formation of trifluorosurfactin in quantities sufficient for detection by LC–MS/MS. 19F NMR analysis of the culture supernatant revealed that the bulk of the fluorinated amino acid was transformed and thus was unavailable for incorporation into surfactin. Detection of ammonia, and MS analysis indicated that the transformation proceeds with deamination and reduction of the keto acid, yielding 4,4,4-trifluoro-2-hydroxy-3-methylbutanoic acid.
    Scopus© Citations 9  563
  • Publication
    Biosynthesis of amphotericin derivatives lacking exocyclic carboxyl groups
    Amphotericin B is a medically important antifungal antibiotic that is also active against human immunodeficiency virus, Leishmania parasites, and prion diseases. The therapeutic use of amphotericin B is restricted by severe side effects that can be moderated by liposomal formulation or structural alteration. Chemical modification has shown that suppression of charge on the exocyclic carboxyl group of amphotericin B substantially reduces toxicity. We report targeted deletions of the amphN cytochrome P450 gene from the chromosome of the amphotericin-producing bacterium Streptomyces nodosus. The mutant strains produced amphotericin analogues in which methyl groups replace the exocyclic carboxyl groups. These compounds retained antifungal activity and had reduced hemolytic activity.
      350Scopus© Citations 100
  • Publication
    Production of lipopeptides in Bacillus sp. CS93 isolated from Pozol
    Bacillus sp. strain CS93, which was previously isolated from Pozol, was previously shown to produce iturin A, bacilysin and chlorotetaine. To investigate the biosynthetic mechanism of chlorotetaine production, the bac genes were amplified from genomic DNA of Bacillus sp. CS93 by PCR and sequenced. The genes bacABCDE were determined, but no gene that might code for a halogenating enzyme was detected either within the gene cluster or in the flanking sequences. Following further analysis of culture supernatants that were active against bacteria by liquid chromatography-MS, it was not possible to detect bacilysin/chlorotetaine. However, in methanolic fractions containing antibacterial activity, molecular ions characteristic of surfactins and fengycin were detectable by electrospray MS. Using primers complementary for conserved regions of nonribosomal peptide synthase, it was possible to amplify gene fragments that had a high degree of homology with known surfactin and fengycin biosynthetic genes. Thus, in addition to the known antimicrobial compounds, we have shown that this strain produces other bioactive lipopeptides, which might account for some of the medicinal properties of Pozol.
    Scopus© Citations 17  815
  • Publication
    Precursor-directed biosynthesis of fluorinated iturin A in Bacillus spp.
    Some iturin A-producing strains of Bacillus subtilis will elaborate the novel fluorinated analogue when incubated with 3-fluoro-L-tyrosine. The activity of iturin A is dependent on the D-tyrosine residue and the presence of fluorotyrosine may result in an improvement of the biological properties of this lipopeptide. The fluorinated iturin might also be used as a probe for studying its interaction with biological membranes.
      1816Scopus© Citations 33