Cebulantin, a Cryptic Lanthipeptide Antibiotic Uncovered Using Bioactivity‐Coupled HiTES

Abstract

The majority of natural product biosynthetic gene clusters in bacteria are silent under standardlaboratory growth conditions,m aking it challenging to uncover any antibiotics that they may encode.Herein, bioactivity assays are combined with high-throughput elicitor screening (HiTES) to access cryptic, bioactive metabolites.A pplication of this strategy in Saccharopolyspora cebuensis,w ith inhibition of Escherichia coli growth as ar ead-out, led to the identification of an ovel lanthipeptide,c ebulantin. Extensive NMR spectroscopic analysis allowed the elucidation of the structure of cebulantin. Subsequent bioactivity assays revealed it to be an antibiotic selective for Gram-negative bacteria, especially against Vibrio species.T his approach, referred to as bioactivity-HiTES,h as the potential to uncover cryptic metabolites with desired biological activities that are hidden in microbial genomes.

Ecology and genomics of Actinobacteria: new concepts for natural product discovery

“…Screening compound libraries for small molecules that perturb antibiotic production was shown to be an effective strategy to identify novel elicitors of antibiotic produciton 111 . Another example is bioactivity highthroughput elicitor screening technology, in which a wild-type microorganism is subjected to a library of small molecules, and the resulting induced metabolomes are screened for bioactivity against a chosen indicator strain 112,113 . Use of this method led to the identification of various cryptic antibiotics, including the novel lanthipeptide cebulantin 112 and the novel naphthoquinone epoxide hiroshidine 113 .…”

“…Another example is bioactivity highthroughput elicitor screening technology, in which a wild-type microorganism is subjected to a library of small molecules, and the resulting induced metabolomes are screened for bioactivity against a chosen indicator strain 112,113 . Use of this method led to the identification of various cryptic antibiotics, including the novel lanthipeptide cebulantin 112 and the novel naphthoquinone epoxide hiroshidine 113 . The method also identified atenolol, a β-blocker clinically used to treat hypertension, as a global elicitor 113 .…”

Physically Adsorbed Metal Ions in Porous Supports as Electrocatalysts for Oxygen Evolution Reaction

“…), but it is still unclear that the promoting effect of OER is from the complex material composition or from the in situ generated thin layers of hydroxide/ oxyhydroxide. Thus, developing an universal and facile approach to obtain the catalysts with highly efficient and well‐defined structure is highly desirable, which not only can satisfy the industrial demands mentioned above, but also can well explore the active sites and mechanism of catalysts …”

Structure Prediction and Synthesis of a New Class of Macrocyclic Peptide Natural Products

“…Together, these advances have led to the discovery of numerous new natural products [24][25][26][27][28] and, in the case of RiPPs, new post-translational modifications. 14,[29][30][31][32][33][34][35] Bioinformatics recently has been utilized to discover new RiPP classes, such as the α-keto β-amino acid-containing peptides, 36 RiPPs generating thiaglutamate by peptide-amino acyl tRNA ligases (PEARLs), 33 aliphatic ether-containing rotapeptides 31 and non-α thioether-containing ranthipeptides, 37 as well as the pyritides, described herein.…”