Stalobacin: Discovery of Novel Lipopeptide Antibiotics with Potent Antibacterial Activity against Multidrug-Resistant Bacteria

Abstract

A novel lipopeptide antibiotic, stalobacin I (1), was discovered from a culture broth of an unidentified Gram-negative bacterium. Stalobacin I (1) had a unique chemical architecture composed of an upper and a lower half peptide sequence, which were linked via a hemiaminal methylene moiety. The sequence of 1 contained an unusual amino acid, carnosadine, 3,4dihydroxyariginine, 3-hydroxyisoleucine, and 3-hydroxyaspartic acid, and a novel cyclopropyl fatty acid. The antibacterial activity of 1 against a broad range of drug-resistant Gram-positive bacteria was much stronger than those of "last resort" antibiotics such as vancomycin, linezolid, and telavancin (MIC 0.004−0.016 μg/mL). Furthermore, compound 1 induced a characteristic morphological change in Gram-positive and Gram-negative strains by inflating the bacterial cell body. The absolute configuration of a cyclopropyl amino acid, carnosadine, was determined by the synthetic study of its stereoisomers, which was an essential component for the strong activity of 1.

“Clicking” an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability

“…Furthermore, in vitro wound healing and dermal permeation assays are under way that will allow us to further demonstrate the expected high value of this unprecedented approach. Finally, the potent action of the compounds herein reported against Gram-negative bacteria is noteworthy, since despite peptide-based structures with potent action against Gram-positive bacteria are being disclosed [ 30 , 31 , 32 , 33 ], the situation is quite different regarding MDR Gram-negative bacteria, against which real alternatives to current antibiotics remain elusive.…”

Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis

“…Some of these drugs have a high market demand including montelukast and ciprofloxacin. Molecules that incorporate this ring in their structure have received considerable attention because they exhibit a wide range of biological activities, including enzymatic inhibition, insecticide, analgesic, antifungal, phytotoxic, antibiotic, antifungal, antiviral, antitumor and hormonal activities [ 13 , 14 , 15 , 16 , 17 , 18 ].…”

Shipworm symbiosis ecology-guided discovery of an antibiotic that kills colistin-resistant Acinetobacter

“…The two remaining residues, β-hydroxyisoleucine and DAHB, both presented challenges due to the lack of any commercially available standards. β-hydroxyisoleucine is rarely found in natural products, and it was reported without stereochemical assignments in stalobactin [21] and the C2 and C3 configurations of this residue were only resolved in phomopsin A through X-ray crystallography. [22] Attempts to grow diffraction-quality crystals were unsuccessful, so investigation of the NRPS domain architecture for the proposed biosynthesis of the turnercyclamycins was used to predict the C2 stereochemistry.…”