Cebulantin, a Cryptic Lanthipeptide Antibiotic Uncovered Using Bioactivity-Coupled HiTES.

Area of Science:

• Microbiology
• Natural Product Chemistry
• Drug Discovery

Background:

• Many bacterial biosynthetic gene clusters remain silent under laboratory conditions, hindering the discovery of novel antibiotics.
• Accessing cryptic metabolites is crucial for identifying new antimicrobial compounds.

Purpose of the Study:

• To develop and apply a novel strategy combining bioactivity assays with high-throughput elicitor screening (HiTES) to uncover silent, bioactive natural products.
• To identify and characterize new antibiotics from the bacterium Saccharopolyspora cebuensis.

Main Methods:

• High-throughput elicitor screening (HiTES) coupled with bioactivity assays.
• NMR spectroscopic analysis for structural elucidation.
• Bacterial growth inhibition assays to determine antibiotic activity.

Main Results:

• Identification of a novel lanthipeptide, named cebulantin, from Saccharopolyspora cebuensis.
• Elucidation of the chemical structure of cebulantin using NMR spectroscopy.
• Cebulantin demonstrated selective antibiotic activity against Gram-negative bacteria, particularly Vibrio species.

Conclusions:

• The bioactivity-HiTES approach is effective in accessing cryptic metabolites from silent gene clusters.
• This strategy holds significant potential for discovering novel bioactive compounds, including antibiotics, from microbial genomes.
• Cebulantin represents a promising new antibiotic candidate for targeting Gram-negative pathogens.