The Bogorol Family of Antibiotics:  Template-Based Structure Elucidation and a New Approach to Positioning Enantiomeric Pairs of Amino Acids

Abstract

The sequence positions of d and l Leu and Lys residues in bogorol A (1) have been defined by a simple and novel approach that utilizes small amounts of sample and focuses on detecting the order in which amino acids are liberated from the parent peptide during acid-catalyzed hydrolysis. This technique builds on a previously established relationship between the steric and electronic features of amino acids and their predilection for acidic liberation from polypeptides via dipeptides. The results, which complete the structure of bogorol A, have been confirmed by traditional degradation experiments. Utilizing the knowledge of the structure of bogorol A (1) as a template, we rapidly elucidated the structures of bogorols B-E (2-5) via analysis of ESI-MS and ESI-MS/MS data and GC analysis of degradation products. The bogorol cationic peptide antibiotics contain a number of unusual structural features, which include the reduction of the C-terminal residue to valinol, an N-terminal residue of 2-hydroxy-3-methylpentanoic acid, the incorporation of four d amino acids, and the presence of a dehydroamino acid. Bogorols show selective and relatively potent activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp., as well as moderate activity against Escherichia coli.

Antifungal activity of Brevibacillus laterosporus JX-5 and characterization of its antifungal components

“…The antifungal substances were isolated from the fermentation broth through a procedure involving ammonium sulfate deposition, CM Sepharose Fast Flow chromatography, and reversed-phase HPLC. Structure analysis through FTIR-MS, MS/MS, and 1 H-NMR and 13 C-NMR showed that the main antifungal substance component B is identical to bogorol B described in the literature (Barsby et al 2006). Bogorols A, B, C, D, and E comprise a group of antibacterial peptides isolated from the cells of the marine bacterium Br.…”

“…Bogorols A, B, C, D, and E comprise a group of antibacterial peptides isolated from the cells of the marine bacterium Br. laterosporus PNG-276 (Barsby et al 2001(Barsby et al , 2006. The structures of the bogorol family are based on the same template.…”

“…The sequence of the compound was determined using the y n and b n ions of MS/MS (Zhao et al 2012). 1 H-NMR and 13 C-NMR spectroscopy was performed on the antifungal components using a JEOL JNM-ECA 600 (600 MHz) NMR spectrometer (JEOL, Japan) (Barsby et al 2006). …”

“…The subtraction of these successive m/z values permitted the assignment of the sequence as 198.11012-Val-Orn-Leu/Ile-Val-ValLys-Val-Leu/Ile-Lys-Tyr-Leu/Ile-104.10439. When searched according the molecular mass and the known amino acids in the data http://www.colby.edu/chemistry/PChem/ Formula.html, a component named bogorol B was found with its molecular weight 1569.0642, and the formula C 79 H 140 N 16 O 16 (Barsby et al 2006). The 1 H-NMR and 13 C-NMR spectra of component B (Online Resource 1 and 2) were then compared with that of bogorol B.…”

Isolation and Structural Elucidation of Brevibacillin, an Antimicrobial Lipopeptide from Brevibacillus laterosporus That Combats Drug-Resistant Gram-Positive Bacteria

“…After careful consideration, we concluded that this new compound is a member of a linear cationic antimicrobial lipopeptide family for which scattered information is available in the published litera- (29) reported the isolation of the first known compound in this family from a marine Bacillus sp. The producer organism was later reclassified as B. laterosporus by the same researchers (30). The lipopeptide was named bogorol A and is different from our brevibacillin in two amino acid resides at positions 5 and 9; isoleucine and valine in brevibacillin are replaced by valine and leucine in bogorol A, respectively.…”