Fumimycin:  A Peptide Deformylase Inhibitor with an Unusual Skeleton Produced by Aspergillus fumisynnematus

Abstract

Fumimycin, an unusual metabolite incorporating an unusual alanine unit linked to a phenyl group at the alpha-carbon with both lactone and amide moieties, was isolated from cultures of Aspergillus fumisynnematus. Its structure was established by spectral analysis. Fumimycin was found to inhibit Staphylococcus aureus peptide deformylase with an IC50 value of 4.1 microM and also showed antibacterial activity against S. aureus.

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

“…Incorporation of such units into peptidomimetics, not only affects lipophilicity, but also the secondary structure and hence the conformational rigidity, which can increase the resistance to enzymatic degradation [15–19]. Such units are also found in biologically interesting natural products, such as the antibacterial fumimycin [20]. …”

Biological characterization of the hygrobafilomycin antibiotic JBIR-100 and bioinformatic insights into the hygrolide family of natural products

“…Importantly, fumaryl substitution is not limited to macrolides, but is present in other polyketides, including reveromycin H–J [94], the antibiotic fumimycin [98], and some nonribosomal peptide natural products such as the thrombin inhibitor Ro 09–1679 [99]. Our attempt to reconcile the molecular and genetic phylogenies of the hygrolide family resulted in the identification of 22 orphan hygrolide gene clusters, indicating that potential remains to find novel hygrolide variants among the Actinomycetes.…”

A Concise Synthesis of (±)-Methoxyfumimycin Ethyl Ester

“…1 It is a potent inhibitor of peptide deformylase (PDF), 2,3 a metalloenzyme essential for prokaryotic growth, but not for mammalian cells. PDF has been regarded as a nontoxic broad-spectrum antibacterial target.…”

“…The combined organic extracts were washed with brine (50 mL), dried over Na 2 SO 4 and concentrated under reduced pressure. Flash chromatography (PE: AcOEt = 4 : 1) afforded the phenol 4 as brown oil (3.06 g, 92%) 1. H NMR δ (CDCl 3 , ppm, 600 MHz): 3.68 (s, 3H), 4.49 (d, J = 6 Hz, 2H), 5.21 (dd, J = 10.2, 1.2 Hz, 1H), 5.32 (dd, J = 17.4, 1.2 Hz, 1H), 5.99-6.05 (m, 1H), 6.34 (dd, J = 8.4, 2.4 Hz, 1H), 6.46 (d, J = 2.4 Hz, 1H), 6.72 (d, J = 8.4 Hz, 1H), 7.20 (brs, 1H).…”