<i>Micromonospora</i>: A Prolific Source of Bioactive Secondary Metabolites with Therapeutic Potential

Yan, Su-Qi; Zeng, Mingyuan; Wang, Hong; Zhang, Huawei

doi:10.1021/acs.jmedchem.2c00626

Cited by 19 publications

(20 citation statements)

References 331 publications

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Section: Discussionmentioning

confidence: 99%

“…To the best of our knowledge, this is the first application of this strategy in Micromonospora strains, resulting in improving the biosynthesis of complex natural products. Since Micromonospora is one of the most prolific producers of bioactive natural products, 69,70 the successful practice of the BGC duplication strategy holds promise to accelerate the discovery and engineering of Micromonospora-derived natural products. Two engineered strains with improved productivity allowed us to isolate six intact EVNs and the corresponding hydrolyzed analogues in sufficient amounts to allow comprehensive in vitro bioactivity evaluation.…”

Section: ■ Discussionmentioning

confidence: 99%

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Biosynthesis and Engineered Overproduction of Everninomicins with Promising Activity against Multidrug-Resistant Bacteria

et al. 2023

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Ribosome-targeting oligosaccharides, everninomicins (EVNs), are promising drug leads with a unique mode of action distinct from that of currently used antibiotics in human therapy. However, the low yields in natural microbial producers hamper an efficient preparation of EVNs for detailed structure− activity relationship analysis. Herein, we enhance the production of EVNs by duplicating the biosynthetic gene cluster (BGC) in Micromonospora sp. SCSIO 07395 and thus obtain multiple EVNs that are sufficient for bioactivity evaluation. EVNs (1−5) are shown to significantly inhibit the growth of multidrug-resistant Gram-positive staphylococcal, enterococcal, and streptococcal strains and Gram-negative pathogens Acinetobacter baumannii and Vibrio cholerae, with micromolar to nanomolar potency, which are comparable or superior to vancomycin, linezolid, and daptomycin. Furthermore, the BGC duplication strategy is proven effective in stepwisely improving titers of the bioactive EVN M (5) from the trace amount to 98.6 mg L −1 . Our findings demonstrate the utility of a bioengineering approach for enhanced production and chemical diversification of the medicinally promising EVNs.

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Section: Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

Biosynthesis and Engineered Overproduction of Everninomicins with Promising Activity against Multidrug-Resistant Bacteria

et al. 2023

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“…exploration, it is now clear that investigations of marine Micromonosporaceae are likely to unveil NPs that differ from those of terrestrial strains, including both general terrestrial bacterial strains and terrestrial Micromonosporaceae Micromonospora spp. [9, 17, 18]. (This study showed that members of the family Micromonosporaceae were more abundant among cultivated bacteria from tropical ecosystems versus brackish ones.…”

Section: Introductionmentioning

confidence: 97%

Micromonosporaceae biosynthetic gene cluster diversity highlights the need for broad-spectrum investigations

Alas,

Braun,

Ericksen

et al. 2024

Microbial Genomics

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Investigations of the bacterial family Micromonosporaceae have enabled the development of secondary metabolites critical to human health. Historical investigation of bacterial families for natural product discovery has focused on terrestrial strains, where time-consuming isolation processes often lead to the rediscovery of known compounds. To investigate the secondary metabolite potential of marine-derived Micromonosporaceae , 38 strains were sequenced, assembled and analysed using antiSMASH and BiG-SLiCE. BiG-SLiCE contains a near-comprehensive dataset of approximately 1.2 million publicly available biosynthetic gene clusters from primarily terrestrial strains. Our marine-derived Micromonosporaceae were directly compared to BiG-SLiCE’s preprocessed database using BiG-SLiCE’s query mode; genetic diversity within our strains was uncovered using BiG-SCAPE and metric multidimensional scaling analysis. Our analysis of marine-derived Micromonosporaceae emphasizes the clear need for broader genomic investigations of marine strains to fully realize their potential as sources of new natural products.

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“…Pyrroles possess a flat and electron-rich aromatic ring, and their structure is susceptible to electrophilic attack and can also interact with a variety of biomolecules via hydrogen bonds as well as π–π stacking interactions [ 19 ]. Because of their intriguing structures and wide range of biomedical properties, various pyrrole-based compounds have been studied for pharmacological activities [ 16 , 20 , 21 , 22 ]. Streptopyrroles are one of the examples of pyrrole-containing compounds with potent antimicrobial properties and inhibitory activity on the nitrogen regulator II (NRII) histidine kinase from Escherichia coli [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Pyrrole-Containing Alkaloids from a Marine-Derived Actinobacterium Streptomyces zhaozhouensis and Their Antimicrobial and Cytotoxic Activities

et al. 2023

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Two new alkaloids, streptopyrroles B and C (1 and 2), were discovered through a chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces zhaozhouensis, along with four known analogs (3–6). The structures of the new compounds were elucidated by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and a comparison of their experimental data with literature values. The new compounds were evaluated for their antimicrobial activity by standard broth dilution assay, and the tested compounds showed significant activity against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 0.7 to 2.9 µM, and kanamycin was used as a positive control with MIC values ranging from <0.5 to 4.1 µM. Additionally, 1, 3, and 5 were evaluated for their cytotoxicity against six tumor cell lines by sulforhodamine B (SRB) assay, and these compounds displayed cytotoxic activities against all the tested cell lines, with concentration causing 50% cell growth inhibition (GI50) values ranging from 4.9 to 10.8 µM, while a positive control, adriamycin, showed GI50 values of 0.13–0.17 µM.

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Micromonospora: A Prolific Source of Bioactive Secondary Metabolites with Therapeutic Potential

Cited by 19 publications

References 331 publications

Biosynthesis and Engineered Overproduction of Everninomicins with Promising Activity against Multidrug-Resistant Bacteria

Biosynthesis and Engineered Overproduction of Everninomicins with Promising Activity against Multidrug-Resistant Bacteria

Micromonosporaceae biosynthetic gene cluster diversity highlights the need for broad-spectrum investigations

Pyrrole-Containing Alkaloids from a Marine-Derived Actinobacterium Streptomyces zhaozhouensis and Their Antimicrobial and Cytotoxic Activities

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