Natural thiopeptides as a privileged scaffold for drug discovery and therapeutic development

Shen, Xiaoqi; Mustafa, Muhammad; Chen, Yanyang; Cao, Yingying; Gao, Jiangtao

doi:10.1007/s00044-019-02361-1

Cited by 25 publications

(29 citation statements)

References 202 publications

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“…3 i) [ [72] , [73] , [74] ]. There is renewed interest in thiopeptide natural products like nosiheptide and siomycin due to their unique biosynthesis, mode of action, and underexploited utility as antibiotics [ 75 ]. The combination of both RiPP and NRPS biosynthetic machineries in one BGC is unique [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…The combination of both RiPP and NRPS biosynthetic machineries in one BGC is unique [ 12 ]. These thiopeptides target ribosomal subunits that are not targeted by any other antibiotics [ 36 ]; however, they are not being used in the clinic due to poor solubility and bioavailability [ 28 , 35 , 75 ]. Chemical modification or bioengineering approaches are being pursued to turn these natural products into next generation antibiotics.…”

Section: Discussionmentioning

confidence: 99%

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Whole genome sequencing of Streptomyces actuosus ISP-5337, Streptomyces sioyaensis B-5408, and Actinospica acidiphila B-2296 reveals secondary metabolomes with antibiotic potential

Majer

Ehrlich

Ahmed

et al. 2021

Biotechnology Reports

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Highlights Whole genome sequencing of Actinomycetes reveals metabolic potential. High quality genomes are necessary for mining of biosynthetic gene clusters. Characterization of thiopeptides by high resolution mass spectrometry. Thiopeptides are potent antibacterials against Staphylococcus aureus .

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Whole genome sequencing of Streptomyces actuosus ISP-5337, Streptomyces sioyaensis B-5408, and Actinospica acidiphila B-2296 reveals secondary metabolomes with antibiotic potential

Majer

Ehrlich

Ahmed

et al. 2021

Biotechnology Reports

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“…Thiopeptides are sulfur-containing, ribosomally-produced and highly posttranslationally modified bacteriocinsantimicrobial peptides produced by bacteria to inhibit other bacteria in competition for nutrients and habitats (12,13). These peptides represent a promising class of natural antibacterial molecules, being active against many Grampositive pathogens, including antibiotic resistant derivatives such as MRSA, vancomycin-resistant enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae (14,15). Thiopeptides inhibit protein synthesis in sensitive bacteria by binding to a cleft between the ribosomal protein L11 and the 23S rRNA, known as the GTPase-associated center, or by binding to and inactivating the elongation factor Tu (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

A Strong Synergy Between the Thiopeptide Bacteriocin Micrococcin P1 and Rifampicin Against MRSA in a Murine Skin Infection Model

et al. 2021

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Antibiotic-resistant bacterial pathogens have become a serious threat worldwide. One of these pathogens is methicillin-resistant Staphylococcus aureus (MRSA), a major cause of skin and soft tissue infections. In this study we identified a strain of Staphylococcus equorum producing a substance with high antimicrobial activity against many Gram-positive bacteria, including MRSA. By mass spectrometry and whole genome sequencing the antimicrobial substance was identified as the thiopeptide bacteriocin micrococcin P1 (MP1). Based on its properties we developed a one-step purification protocol resulting in high yield (15 mg/L) and high purity (98%) of MP1. For shorter incubation times (5-7 h) MP1 was very potent against MRSA but the inhibitory effect was overshadowed by resistance development during longer incubation time (24h or more). To overcome this problem a synergy study was performed with a number of commercially available antibiotics. Among the antibiotics tested, the combination of MP1 and rifampicin gave the best synergistic effect, with MIC values 25 and 60 times lower than for the individual drugs, respectively. To assess the therapeutic potential of the MP1-rifampicin combination, we used a murine skin infection model based on the use of the multidrug-resistant luciferase-tagged MRSA strain Xen31. As expected, neither of the single antimicrobials (MP1 or rifampicin) could eradicate Xen31 from the wounds. By contrary, the MP1-rifampicin combination was efficient not only to eradicate but also to prevent the recurrence of Xen31 infection. Furthermore, compared to fucidin cream, which is commonly used in skin infection treatments, MP1-rifampicin combination was superior in terms of preventing resistance development. Our results show that combining MP1, and probably other thiopeptides, with antibiotics can be a promising strategy to treat SSTIs caused by MRSA and likely many other Gram-positive bacteria.

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“…Thiazolyl peptides also show other interesting properties such as antiplasmodial and anticancer activities. [ 18 ] Bicyclic peptides form an important class of therapeutic agents with marketed products such as actinomycin, endothelin, and vancomycin. A number of such compounds that therapeutically target HIV (cycloviolin) and tumors (moroidin ( 8 )) are in early stage of development (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Structural and biological aspects of natural bridged macrobicyclic peptides from marine resources

Dahiya

Kumar

et al. 2021

Archiv der Pharmazie

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Among peptide‐based drugs, naturally occurring bicyclic compounds have been established as molecules with unique therapeutic potential. The diverse pharmacological activities associated with bicyclic peptides from marine tunicates, sponges, and bacteria render them suitable to be employed as effective surrogate between complex and small therapeutic moieties. Bicyclic peptides possess greater conformational rigidity and higher metabolic stability as compared with linear and monocyclic peptides. The antibody‐like affinity and specificity of bicyclic peptides enable their binding to the challenging drug targets. Bridged macrobicyclic peptides from natural marine resources represent an underexplored class of molecules that provides promising platforms for drug development owing to their biocompatibility, similarity, and chemical diversity to proteins. The present review explores major marine‐derived bicyclic peptides including disulfide‐bridged, histidinotyrosine‐bridged, or histidinoalanine‐bridged macrobicyclic peptides along with their structural characteristics, synthesis, structure–activity relationship, and bioproperties.The comparison of these macrobicyclic congeners with linear/monocyclic peptides along with their therapeutic potential are also briefly discussed.

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Natural thiopeptides as a privileged scaffold for drug discovery and therapeutic development

Cited by 25 publications

References 202 publications

Whole genome sequencing of Streptomyces actuosus ISP-5337, Streptomyces sioyaensis B-5408, and Actinospica acidiphila B-2296 reveals secondary metabolomes with antibiotic potential

Whole genome sequencing of Streptomyces actuosus ISP-5337, Streptomyces sioyaensis B-5408, and Actinospica acidiphila B-2296 reveals secondary metabolomes with antibiotic potential

A Strong Synergy Between the Thiopeptide Bacteriocin Micrococcin P1 and Rifampicin Against MRSA in a Murine Skin Infection Model

Structural and biological aspects of natural bridged macrobicyclic peptides from marine resources

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