Comparative Genomic and Metabolic Analysis of <i>Streptomyces</i> sp. RB110 Morphotypes Illuminates Genomic Rearrangements and Formation of a New 46-Membered Antimicrobial Macrolide

Um, Sung Hee; Guo, Huijuan; Thiengmag, Sirinthra; Benndorf, René; Murphy, Robert S.; Rischer, Maja; Braga, Daniel; Poulsen, Michael; Beer, Z. Wilhelm de; Lackner, Gerald; Beemelmanns, Christine

doi:10.1021/acschembio.1c00357

Cited by 6 publications

(4 citation statements)

References 50 publications

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“…Full-length sequence analysis of the DHs demonstrated that the ActnS0DH1 harbored the "conserved" amino acid sequence and thus should be functional (Figure S7). Similar active DH domains that are retained in the cluster but serve no function could also be found in the NysA for nystatin [24] and the TrmB for termidomycin [30].…”

Section: Proposed Model For Biosynthetic Pathway Of Actinospenementioning

confidence: 67%

The Discovery of Actinospene, a New Polyene Macrolide with Broad Activity against Plant Fungal Pathogens and Pathogenic Yeasts

et al. 2021

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Phytopathogenic fungi infect crops, presenting a worldwide threat to agriculture. Polyene macrolides are one of the most effective antifungal agents applied in human therapy and crop protection. In this study, we found a cryptic polyene biosynthetic gene cluster in Actinokineospora spheciospongiae by genome mining. Then, this gene cluster was activated via varying fermentation conditions, leading to the discovery of new polyene actinospene (1), which was subsequently isolated and its structure determined through spectroscopic techniques including UV, HR-MS, and NMR. The absolute configuration was confirmed by comparing the calculated and experimental electronic circular dichroism (ECD) spectra. Unlike known polyene macrolides, actinospene (1) demonstrated more versatile post-assembling decorations including two epoxide groups and an unusual isobutenyl side chain. In bioassays, actinospene (1) showed a broad spectrum of antifungal activity against several plant fungal pathogens as well as pathogenic yeasts with minimum inhibitory concentrations ranging between 2 and 10 μg/mL.

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Section: Proposed Model For Biosynthetic Pathway Of Actinospenementioning

confidence: 67%

The Discovery of Actinospene, a New Polyene Macrolide with Broad Activity against Plant Fungal Pathogens and Pathogenic Yeasts

et al. 2021

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“…Subsequently, multiple sequence alignments of the KR domains were used to predict the absolute configuration of the hydroxy-bearing stereocenters of demurilactone A, based on the conserved regions of KRs that direct the stereochemistry. − This approach has been used to propose the absolute configuration of several macrolides including termidomycin A, niphimycins, brasilinolides, caniferolides, and quinolidomicin . Based on the presence of the Leu-Asp-Asp (LDD) motif in the loop region and the absence of tryptophan (W) and the YXP motifs in the catalytic region, the KRs of modules 4, 6, 7, 9, 11, 12, 13, and 14 were assigned as B1 type (Table S6).…”

Section: Resultsmentioning

confidence: 99%

Discovery of Demurilactone A: A Specific Growth Inhibitor of L-Form Bacillus subtilis

Dashti

Tajabadi²,

et al. 2022

ACS Infect. Dis.

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Metabolic profiling of the extracts from a library of actinobacteria led to the identification of a novel polyketide, demurilactone A, produced by Streptomyces strain DEM21308. The structure of the compound was assigned based on a detailed investigation of 1D/2D NMR spectra and HR-MS. Whole genome DNA sequencing, followed by bioinformatics analysis and insertional mutagenesis, identified type I polyketide synthases encoded by the dml gene cluster to direct the biosynthesis of this polyene macrolide. While the number of modules is consistent with the carbon backbone of the assigned structure, some discrepancies were identified in the domain organization of five modules. Close investigation of the amino acid sequences identified several mutations in the conserved motifs of nonfunctional domains. Furthermore, the absolute configuration of hydroxy-bearing stereocenters was proposed based on analyses of the ketoreductase domains. Remarkably, although demurilactone A has little detectable activity against normal-walled bacteria, it specifically inhibits the growth of cell wall-deficient "L-form" Bacillus subtilis at a minimum inhibitory concentration value of 16 μg/mL. Time-lapse microscopy analyses revealed that demurilactone affects membrane dynamics, probably by reducing membrane fluidity. This compound could be a powerful reagent for studying longstanding questions about the involvement of L-forms in recurrent infection.

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“…Edison et al [31] used in-silico analysis in structural elucidation. Some researchers used comparative genomics in their studies [32][33][34][35][36][37]. Kumar et al [38] used in vitro and insilico analysis using machine learning in their studies.…”

Section: Streptomyces Lividans -Streptomyces Coelicolor Andmentioning

confidence: 99%

Novel Drug Development for Treatment of COVID-19 by In Silico Analysis: Identification of SARS-Cov-2 Inhibiting Streptomyces Compounds

Kumar

Gholap

Pillai

2023

Journal of Cellular Signaling

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In accordance with the present epidemiological paradigm, viral mutations of the virus are on the rise, and their natural effects are being selected for at a higher rate than normal. According to the World Health Organization (WHO), the global COVID-19 pandemic induced by the Delta and Omicron strain of the SARS-CoV-2 virus could propagate and disseminate more rapidly than other viruses thanks to its many mutations, and these also caused some very significant health problems. The established medications would eventually start to lose their efficacy since the variation mutated more quickly than the original stain. As protein spikes are the point of origin or epitome for the mutations to take place, it would be most effective to target the remaining vital enzymes by binding the proteins with the largest pocket sizes. The objective of the current work is to employ in-silico analysis to discover the streptomyces chemicals that suppress the SARS-CoV-2 virus as well as its mutated strains thus promoting a healthy body. Based on the drug likeness property of compounds when subjected to molecular docking, a total of 14 compounds were identified and selected from the PUBCHEM database that showed highest binding energy with the targeted Receptor Binding Domain. The compounds namely - Streptomyces tanashiensis; Thaxtomin A; Bafilomycin A1 from Streptomyces griseus and few others as mentioned further on more research would support and confirm the utilizing of these to create new medications to treat the novel SARS-CoV-2 infectious strains.

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Comparative Genomic and Metabolic Analysis of Streptomyces sp. RB110 Morphotypes Illuminates Genomic Rearrangements and Formation of a New 46-Membered Antimicrobial Macrolide

Cited by 6 publications

References 50 publications

The Discovery of Actinospene, a New Polyene Macrolide with Broad Activity against Plant Fungal Pathogens and Pathogenic Yeasts

The Discovery of Actinospene, a New Polyene Macrolide with Broad Activity against Plant Fungal Pathogens and Pathogenic Yeasts

Discovery of Demurilactone A: A Specific Growth Inhibitor of L-Form Bacillus subtilis

Novel Drug Development for Treatment of COVID-19 by In Silico Analysis: Identification of SARS-Cov-2 Inhibiting Streptomyces Compounds

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