Genome mining for the search and discovery of bioactive compounds: The Streptomyces paradigm

Ward, AC; Allenby, NE

doi:10.1093/femsle/fny240

Cited by 56 publications

(51 citation statements)

References 138 publications

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“…SCSIO 40010 and the absolute configuration at C-10 in these PTMs was identified as being 10S, opposite to their known PTM congeners. These observations further highlight the importance of Streptomyces species as prolific sources for bioactive compounds and they indicate the worth of genome mining in marine-derived Streptomycetes [35]. Similar to the well-established biosynthetic pathway for 5/5/6 type of PTMs [20,23,33], PtmA catalyzes the formation of a common polyene tetramate precursor, which is sequentially cyclized by PtmB2 /PtmB1 into an intermediate with the 5/5 carbocyclic ring system (Figure 2b).…”

Section: Biosynthetic Implicationsmentioning

confidence: 62%

Genome Mining of Marine-Derived Streptomyces sp. SCSIO 40010 Leads to Cytotoxic New Polycyclic Tetramate Macrolactams

Liu

Zhang²,

Jin³

et al. 2019

Marine Drugs

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Polycyclic tetramate macrolactams (PTMs) biosynthetic gene cluster are widely distributed in different bacterial types, especially in Streptomyces species. The mining of the genomic data of marine-derived Streptomyces sp. SCSIO 40010 reveals the presence of a putative PTM-encoding biosynthetic gene cluster (ptm′ BGC) that features a genetic organization for potentially producing 5/5/6 type of carbocyclic ring-containing PTMs. A fermentation of Streptomyces sp. SCSIO 40010 led to the isolation and characterization of six new PTMs 1–6. Comprehensive spectroscopic analysis assigned their planar structures and relative configurations, and their absolute configurations were deduced by comparing the experimental electronic circular dichroism (ECD) spectra with the reported spectra of the known PTMs. Intriguingly, compounds 1–6 were determined to have a trans-orientation of H-10/H-11 at the first 5-membered ring, being distinct from the cis-orientation in their known PTM congeners. PTMs 1–5 displayed cytotoxicity against several cancer cell lines, with IC50 values that ranged from 2.47 to 17.68 µM.

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Section: Biosynthetic Implicationsmentioning

confidence: 62%

Genome Mining of Marine-Derived Streptomyces sp. SCSIO 40010 Leads to Cytotoxic New Polycyclic Tetramate Macrolactams

Liu

Zhang²,

Jin³

et al. 2019

Marine Drugs

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“…These genes encode for the enzymes involved in peptide assembly, regulation, resistance, and synthesis of a secondary metabolite, and are physically clustered into groups called biosynthetic gene clusters (BGCs) 10 . Recent studies involving mining of large-scale genomic datasets have highlighted the tremendous potential of discovering novel and potentially relevant compounds from microbes 9,[11][12][13] , which can allay some of the challenges in antibiotic development today 14,15 . While it has been estimated that many more novel natural products remain to be uncovered and functionally characterized, particularly those from poorly studied ecological niches, it is uncertain what the true number is or whether ongoing drug discovery efforts are reaching BGC saturation 16 .…”

mentioning

confidence: 99%

Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria

Belknap

Park

Barth

et al. 2020

Sci Rep

163

103

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Streptomyces bacteria are known for their prolific production of secondary metabolites, many of which have been widely used in human medicine, agriculture and animal health. To guide the effective prioritization of specific biosynthetic gene clusters (BGCs) for drug development and targeting the most prolific producer strains, knowledge about phylogenetic relationships of Streptomyces species, genomewide diversity and distribution patterns of BGcs is critical. We used genomic and phylogenetic methods to elucidate the diversity of major classes of BGCs in 1,110 publicly available Streptomyces genomes. Genome mining of Streptomyces reveals high diversity of BGcs and variable distribution patterns in the Streptomyces phylogeny, even among very closely related strains. The most common BGCs are non-ribosomal peptide synthetases, type 1 polyketide synthases, terpenes, and lantipeptides. We also found that numerous Streptomyces species harbor BGcs known to encode antitumor compounds. We observed that strains that are considered the same species can vary tremendously in the BGcs they carry, suggesting that strain-level genome sequencing can uncover high levels of BGC diversity and potentially useful derivatives of any one compound. These findings suggest that a strain-level strategy for exploring secondary metabolites for clinical use provides an alternative or complementary approach to discovering novel pharmaceutical compounds from microbes.

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“…coelicolor ) with the reference hopene BGC (BGC0000663) in the MIBiG database. Hopenes play roles in maintaining membrane fluidity and stability [ 101 ], and their BGCs are one of the most abundant BGCs observed in Streptomyces along with those for ectoine [ 102 ]. Ectoine BGCs are highly conserved in Streptomyces and prevent osmotic stress [ 103 ].…”

Section: Resultsmentioning

confidence: 99%

“…Despite the fact that the number of Streptacidiphilus genomes are limited at present, the overall distribution of known BGCs was different from Streptomyces . For example, BGCs such as those for albaflavenone and melanin which are otherwise abundant in Streptomyces [ 102 ] were not identified in any of the Streptacidiphilus species. On the other hand, only one melanin type BGC was found within the Kitasatospora ( Kitasatospora mediocidica KCTC 9733 T ) genome.…”

Section: Resultsmentioning

confidence: 99%

Genome Mining of the Genus Streptacidiphilus for Biosynthetic and Biodegradation Potential

Malik

Kim

2020

Genes

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The genus Streptacidiphilus represents a group of acidophilic actinobacteria within the family Streptomycetaceae, and currently encompasses 15 validly named species, which include five recent additions within the last two years. Considering the potential of the related genera within the family, namely Streptomyces and Kitasatospora, these relatively new members of the family can also be a promising source for novel secondary metabolites. At present, 15 genome data for 11 species from this genus are available, which can provide valuable information on their biology including the potential for metabolite production as well as enzymatic activities in comparison to the neighboring taxa. In this study, the genome sequences of 11 Streptacidiphilus species were subjected to the comparative analysis together with selected Streptomyces and Kitasatospora genomes. This study represents the first comprehensive comparative genomic analysis of the genus Streptacidiphilus. The results indicate that the genomes of Streptacidiphilus contained various secondary metabolite (SM) producing biosynthetic gene clusters (BGCs), some of them exclusively identified in Streptacidiphilus only. Several of these clusters may potentially code for SMs that may have a broad range of bioactivities, such as antibacterial, antifungal, antimalarial and antitumor activities. The biodegradation capabilities of Streptacidiphilus were also explored by investigating the hydrolytic enzymes for complex carbohydrates. Although all genomes were enriched with carbohydrate-active enzymes (CAZymes), their numbers in the genomes of some strains such as Streptacidiphilus carbonis NBRC 100919T were higher as compared to well-known carbohydrate degrading organisms. These distinctive features of each Streptacidiphilus species make them interesting candidates for future studies with respect to their potential for SM production and enzymatic activities.

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Genome mining for the search and discovery of bioactive compounds: The Streptomyces paradigm

Cited by 56 publications

References 138 publications

Genome Mining of Marine-Derived Streptomyces sp. SCSIO 40010 Leads to Cytotoxic New Polycyclic Tetramate Macrolactams

Genome Mining of Marine-Derived Streptomyces sp. SCSIO 40010 Leads to Cytotoxic New Polycyclic Tetramate Macrolactams

Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria

Genome Mining of the Genus Streptacidiphilus for Biosynthetic and Biodegradation Potential

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