Correction: NocU is a cytochrome P450 oxygenase catalyzing N-hydroxylation of the indolic moiety during the maturation of the thiopeptide antibiotics nocathiacins

Correction for ‘NocU is a cytochrome P450 oxygenase catalyzing N-hydroxylation of the indolic moiety during the maturation of the thiopeptide antibiotics nocathiacins’ by Heng Guo et al., Org. Biomol. Chem., 2021, DOI: 10.1039/d1ob01284c.

NocU is a Cytochrome P450 Oxygenase Catalyzing N-Hydroxylation of the Indolic Moiety during the Maturation of the Thiopeptide Antibiotics Nocathiacins

The ribosomally synthesized and post-translationally modified peptide (RiPP) natural products include the family of thiopeptide antibiotics, where nocathiacins (NOCs) and nosiheptide (NOS) are structurally related bicyclic members featuring an indolic...

Host-dependent Heterologous Expression of Berninamycin Gene Cluster Leads to Linear Thiopeptide Antibiotics

Berninamycins are a class of thiopeptide antibiotics with potent activity against Gram-positive bacteria. Heterologous expression of the berninamycin (ber) biosynthetic gene cluster from marine-derived Streptomyces sp. SCSIO 11878 in different...

Diversity-Oriented Routes to Thiopeptide Antibiotics: Total Synthesis and Biological Evaluation of Micrococcin P2

We report the first total synthesis of micrococcin P2 (MP2, 1) by a diversity-oriented route that incorporates a number of refinements relative to earlier syntheses. Biological data regarding the activity...

A New Thiopeptide Antibiotic, Micrococcin P3, from a Marine-Derived Strain of the Bacterium Bacillus stratosphericus

A new thiopeptide (micrococcin P3, 1) and a known one (micrococcin P1, 2) were isolated from the culture broth of a marine-derived strain of Bacillus stratosphericus. The structures of both compounds were elucidated using spectroscopic methods, including extensive 1D and 2D NMR analysis, high resolution mass spectrometry (HRMS), and tandem mass spectrometry. Both compounds exhibited potent antibacterial activities against Gram-positive strains with minimum inhibitory concentration (MIC) values of 0.05−0.8 μg/mL and did not show cytotoxicity in the MTT assay up to a concentration of 10 μM. This study adds a new promising member, micrococcin P3, to the family of thiopeptide antibiotics, which shows potential for the development of new antibiotics targeting Gram-positive bacteria.

Litoralimycins A and B, New Cytotoxic Thiopeptides from Streptomonospora sp. M2

Streptomonospora sp. M2 has been isolated from a soil sample collected at the Wadden Sea beach in our ongoing program aimed at the isolation of rare Actinobacteria, ultimately targeting the discovery of new antibiotics. Because crude extracts derived from cultures of this strain showed inhibitory activity against the indicator organism Bacillus subtilis, it was selected for further analysis. HPLC–MS analysis of its culture broth revealed the presence of lipophilic metabolites. The two major metabolites of those were isolated by preparative reversed-phase HPLC and preparative TLC. Their planar structures were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D NMR data as new thiopeptide antibiotics and named litoralimycin A (1) and B (2). Although rotating frame nuclear Overhauser effect spectroscopy (ROESY) data established a Z configuration of the Δ21,26 double bond, the stereochemistry of C-5 and C-15 were assigned as S by Marfey’s method after ozonolysis. The biological activity spectrum of 1 and 2 is highly uncommon for thiopeptide antibiotics, since they showed only insignificant antibacterial activity, but 1 showed strong cytotoxic effects.

Thiopeptide Defense by an Ant’s Bacterial Symbiont

Fungus-growing ants and their bacterial symbionts have emerged as a model animal-microbe symbiosis and an ideal system for understanding antibiotic deployment in an ecological context. We found that <i>Pseudonocardia</i> symbionts of the ant <i>Trachymyrmex septentrionalis</i> have strong antibiotic activity against their most likely competitors: other strains of ant-associated bacteria. Activity-guided fractionation revealed the defensive molecule produced by these bacteria to be the thiopeptide antibiotic GE37468. Here we assign an ecological role – host-associated niche defense – for this antibiotic, previously identified in a biochemical screen and known only for its <i>in vitro </i>activity against clinically-relevant pathogens. Genomic analysis uncovered a split biosynthetic gene cluster for this molecule and suggests that these symbionts acquired it from soil bacteria. Similar thiopeptide antibiotics have recently been ascribed host-associated niche defense roles, and the function of GE37468 in this insect niche intriguingly parallels thiopeptide defense in the human microbiome. Molecular defenses from animal-associated microbes may have particular promise as therapeutics, and indeed thiopeptide antibiotics with high structural similarity to GE37468 are already under clinical investigation.

Thiopeptide Defense by an Ant’s Bacterial Symbiont

Fungus-growing ants and their bacterial symbionts have emerged as a model animal-microbe symbiosis and an ideal system for understanding antibiotic deployment in an ecological context. We found that <i>Pseudonocardia</i> symbionts of the ant <i>Trachymyrmex septentrionalis</i> have strong antibiotic activity against their most likely competitors: other strains of ant-associated bacteria. Activity-guided fractionation revealed the defensive molecule produced by these bacteria to be the thiopeptide antibiotic GE37468. Here we assign an ecological role – host-associated niche defense – for this antibiotic, previously identified in a biochemical screen and known only for its <i>in vitro </i>activity against clinically-relevant pathogens. Genomic analysis uncovered a split biosynthetic gene cluster for this molecule and suggests that these symbionts acquired it from soil bacteria. Similar thiopeptide antibiotics have recently been ascribed host-associated niche defense roles, and the function of GE37468 in this insect niche intriguingly parallels thiopeptide defense in the human microbiome. Molecular defenses from animal-associated microbes may have particular promise as therapeutics, and indeed thiopeptide antibiotics with high structural similarity to GE37468 are already under clinical investigation.

Optimal design of thiostrepton-derived thiopeptide antibiotics and their potential application against oral pathogens

A new fluorinated thiostrepton-type thiopeptide antibiotic was designed and biosynthesized by using a biological approach with synthetic advantages. Related bioassays indicated that thiostrepton and its derivatives hold potential in oral pathogen treatment.