scholarly journals Integrated metabolomic, molecular networking and genome mining analyses uncover novel angucyclines from Streptomyces sp. RO-S4 isolated from Bejaia Bay, Algeria

2021 ◽  
Author(s):  
Rima Ouchene ◽  
Didier Stien ◽  
Juliette Segret ◽  
Mouloud Kecha ◽  
Alice MS Rodrigues ◽  
...  
Keyword(s):  
Ring Opening ◽  
Draft Genome ◽  
Genome Mining ◽  
Gene Clusters ◽  
Diffusion Method ◽  
Biosynthetic Gene ◽  
Metabolic Potential ◽  
Molecular Networking ◽  
Streptomyces Sp ◽  
A Genome

Multi-omic approaches have recently made big strides towards the effective exploration of microorganisms and accelerating the discovery of new bioactive compounds. We combined metabolomic, molecular networking, and genomic-based approaches to investigate the metabolic potential of the Streptomyces sp. RO-S4 strain isolated from the polluted waters of Bejaia Bay in Algeria. Antagonistic assays against methicillin-resistant Staphylococcus aureus with RO-S4 organic extracts showed an inhibition zone of 20 mm by the agar diffusion method, and its minimum inhibitory concentration was 16 μg/mL. A molecular network was created using GNPS and annotated through the comparison of MS/MS spectra against several databases. The predominant compounds in the RO-S4 extract belonged to the angucyclines family. Three compounds were annotated as known metabolites, while all the others were putatively new to Science. Notably, all compounds had fridamycin-like aglycones, and several of them had a lactonized D ring analogous to that of urdamycin L. The whole genome of Streptomyces RO-S4 was sequenced to identify the biosynthetic gene cluster (BGC) encoding for these angucyclines, which yielded a draft genome of 7,497,846 bp with 72.4% G+C content. Subsequently, a genome mining analysis revealed 19 putative biosynthetic gene clusters, including a grincamycin-like BGC with a high similarity to that of Streptomyces sp. CZN-748 previously reported to also produce mostly open fridamycin-like aglycones. As the ring-opening process leading to these compounds is still not defined, we performed comparative analysis with other angucycline BGCs and advanced some hypotheses to explain the ring-opening and lactone formation, possibly linked to the uncoupling between the activity of GcnE and GcnM homologues in the RO-S4 strain. The combination of metabolomic and genomic approaches greatly improved the interpretation of the metabolic potential of the RO-S4 strain.

scholarly journals Whole-genome sequence of bioactive streptomycete derived from mangrove forest in Malaysia, Streptomyces sp. MUSC 14

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hooi-Leng Ser ◽  
Loh Teng-Hern Tan ◽  
Wen-Si Tan ◽  
Wai-Fong Yin ◽  
Kok-Gan Chan
Keyword(s):  
East Coast ◽  
Genetic Manipulation ◽  
Genome Mining ◽  
Gene Clusters ◽  
Peninsular Malaysia ◽  
Whole Genome Sequence ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Streptomyces Sp ◽  
A Genome

The contribution of streptomycetes to human health is undeniably important and significant, given that these filamentous microbes can produce interesting compounds that can be used to cure deadly infections and even cancer. Isolated from the east coast of Peninsular Malaysia, Streptomyces sp. MUSC 14 has shown significant antioxidant capacity. The current study explores the genomic potential of MUSC 14 via a genome mining approach. The genome size of MUSC 14 is 10,274,825 bp with G + C content of 71.3 %. AntiSMASH analysis revealed a total of nine biosynthetic gene clusters (with more than 80 % similarities to known gene clusters). This information serves as an important foundation for subsequent studies, particularly the purification and isolation of bioactive compounds by genetic manipulation techniques.

scholarly journals Draft Genome Sequence of Streptomyces sp. TP-A0874, a Catechoserine Producer

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Hisayuki Komaki ◽  
Akira Hosoyama ◽  
Natsuko Ichikawa ◽  
Yasuhiro Igarashi
Keyword(s):  
Genome Sequence ◽  
Cell Invasion ◽  
Draft Genome ◽  
Gene Clusters ◽  
Bioinformatic Analysis ◽  
Biosynthetic Gene Cluster ◽  
Tumor Cell Invasion ◽  
Draft Genome Sequence ◽  
Biosynthetic Gene ◽  
Streptomyces Sp

We report the draft genome sequence of Streptomyces sp. TP-A0874 isolated from compost. This strain produces catechoserine, a new catecholate-type inhibitor of tumor cell invasion. The genome harbors at least six gene clusters for polyketide and nonribosomal peptide biosyntheses. The biosynthetic gene cluster for catechoserines was identified by bioinformatic analysis.

scholarly journals Activation and Identification of a Griseusin Cluster in Streptomyces sp. CA-256286 by Employing Transcriptional Regulators and Multi-Omics Methods

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6580
Author(s):  
Charlotte Beck ◽  
Tetiana Gren ◽  
Francisco Javier Ortiz-López ◽  
Tue Sparholt Jørgensen ◽  
Daniel Carretero-Molina ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Genome Mining ◽  
Gene Clusters ◽  
Transcriptional Regulators ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Heterologous Host ◽  
Streptomyces Sp ◽  
Identification And Characterization

Streptomyces are well-known producers of a range of different secondary metabolites, including antibiotics and other bioactive compounds. Recently, it has been demonstrated that “silent” biosynthetic gene clusters (BGCs) can be activated by heterologously expressing transcriptional regulators from other BGCs. Here, we have activated a silent BGC in Streptomyces sp. CA-256286 by overexpression of a set of SARP family transcriptional regulators. The structure of the produced compound was elucidated by NMR and found to be an N-acetyl cysteine adduct of the pyranonaphtoquinone polyketide 3′-O-α-d-forosaminyl-(+)-griseusin A. Employing a combination of multi-omics and metabolic engineering techniques, we identified the responsible BGC. These methods include genome mining, proteomics and transcriptomics analyses, in combination with CRISPR induced gene inactivations and expression of the BGC in a heterologous host strain. This work demonstrates an easy-to-implement workflow of how silent BGCs can be activated, followed by the identification and characterization of the produced compound, the responsible BGC, and hints of its biosynthetic pathway.

scholarly journals Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

2020 ◽  
Author(s):  
Yunchang Xie ◽  
Jiawen Chen ◽  
Bo Wang ◽  
Tai Chen ◽  
Junyu Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Mutant Strain ◽  
Genome Mining ◽  
Gene Clusters ◽  
Immunosuppressive Drug ◽  
Biosynthetic Gene ◽  
Bioactive Natural Products ◽  
Drug Lead ◽  
A Genome ◽  
Mining Work

Abstract Backgrounds: Activation of silent biosynthetic gene clusters (BGCs) in marine-derived actinomycete strains is a feasible strategy to discover bioactive natural products. Actinoalloteichus sp. AHMU CJ021, isolated from the seashore, was shown to contain an intact but silent caerulomycin A (CRM A) BGC-cam in its genome. Thus, a genome mining work was preformed to activate the strain’s bioproduction of CRM A, an immunosuppressive drug lead with diverse bioactivities.Results: To well activate the expression of cam, ribosomal engineering was adopted to treat the wild type Actinoalloteichus sp. AHMU CJ021. The initial mutant strain XC-11G with gentamycin resistance and CRM A bioproduction titer of 42.51 ± 4.22 mg/L was selected from all generated mutant strains by gene expression comparison of the essential biosynthetic gene-camE. The titer of CRM A bioproduction was then improved by two strain breeding methods via UV mutagenesis and cofactor engineering-directed increasing of intracellular riboflavin, which finally generated the optimal mutant strain XC-11GUR with a CRM A bioproduction titer of 113.91 ± 7.58 mg/L. Subsequently, this titer of strain XC-11GUR was improved to 618.61 ± 16.29 mg/L through medium optimization together with further adjustment derived from response surface methodology. In terms of this 14.7 folds increase in the titer of CRM A compared to the initial value, strain XC-GUR could be a well alternative strain for CRM A development.Conclusions: Our results have constructed an ideal CRM A producer. More importantly, our efforts also have demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.

scholarly journals Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

2020 ◽  
Author(s):  
Yunchang Xie ◽  
Jiawen Chen ◽  
Bo Wang ◽  
Tai Chen ◽  
Junyu Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Mutant Strain ◽  
Genome Mining ◽  
Gene Clusters ◽  
Immunosuppressive Drug ◽  
Biosynthetic Gene ◽  
Bioactive Natural Products ◽  
Drug Lead ◽  
A Genome ◽  
Mining Work

Abstract Backgrounds: Activation of silent biosynthetic gene clusters (BGCs) in marine-derived actinomycete strains is a feasible strategy to discover bioactive natural products. Actinoalloteichus sp. AHMU CJ021, isolated from the seashore, was shown to contain an intact but silent caerulomycin A (CRM A) BGC-cam in its genome. Thus, a genome mining work was preformed to activate the strain’s production of CRM A, an immunosuppressive drug lead with diverse bioactivities.Results: To well activate the expression of cam, ribosome engineering was adopted to treat the wild type Actinoalloteichus sp. AHMU CJ021. The initial mutant strain XC-11G with gentamycin resistance and CRM A production titer of 42.51 ± 4.22 mg/L was selected from all generated mutant strains by gene expression comparison of the essential biosynthetic gene-camE. The titer of CRM A production was then improved by two strain breeding methods via UV mutagenesis and cofactor engineering-directed increase of intracellular riboflavin, which finally generated the optimal mutant strain XC-11GUR with a CRM A production titer of 113.91 ± 7.58 mg/L. Subsequently, this titer of strain XC-11GUR was improved to 618.61 ± 16.29 mg/L through medium optimization together with further adjustment derived from response surface methodology. In terms of this 14.6 folds increase in the titer of CRM A compared to the initial value, strain XC-GUR could be a well alternative strain for CRM A development.Conclusions: Our results have constructed an ideal CRM A producer. More importantly, our efforts also have demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.

scholarly journals Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

2020 ◽  
Author(s):  
Yunchang Xie ◽  
Jiawen Chen ◽  
Bo Wang ◽  
Tai Chen ◽  
Junyu Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Mutant Strain ◽  
Genome Mining ◽  
Gene Clusters ◽  
Immunosuppressive Drug ◽  
Biosynthetic Gene ◽  
Bioactive Natural Products ◽  
Drug Lead ◽  
A Genome ◽  
Mining Work

Abstract Backgrounds: Activation of silent biosynthetic gene clusters (BGCs) in marine-derived actinomycete strains is a feasible strategy to discover bioactive natural products. Actinoalloteichus sp. AHMU CJ021, isolated from the seashore, was shown to contain an intact but silent caerulomycin A (CRM A) BGC- cam in its genome. Thus, a genome mining work was preformed to activate the strain’s production of CRM A, an immunosuppressive drug lead with diverse bioactivities.Results: To well activate the expression of cam , ribosome engineering was adopted to treat the wild type Actinoalloteichus sp. AHMU CJ021. The initial mutant strain XC-11G with gentamycin resistance and CRM A production titer of 42.51 ± 4.22 mg/L was selected from all generated mutant strains by gene expression comparison of the essential biosynthetic gene-camE. The titer of CRM A production was then improved by two strain breeding methods via UV mutagenesis and cofactor engineering-directed increase of intracellular riboflavin, which finally generated the optimal mutant strain XC-11GUR with a CRM A production titer of 113.91 ± 7.58 mg/L. Subsequently, this titer of strain XC-11GUR was improved to 618.61 ± 16.29 mg/L through medium optimization together with further adjustment derived from response surface methodology. In terms of this 14.6 folds increase in the titer of CRM A compared to the initial value, strain XC-GUR could be a well alternative strain for CRM A development.Conclusions: Our results have constructed an ideal CRM A producer. More importantly, our efforts also have demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.

scholarly journals Genome Mining, Microbial Interactions, and Molecular Networking Reveals New Dibromoalterochromides from Strains of Pseudoalteromonas of Coiba National Park-Panama

Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 456
Author(s):  
Librada A. Atencio ◽  
Cristopher A. Boya P. ◽  
Christian Martin H. ◽  
Luis C. Mejía ◽  
Pieter C. Dorrestein ◽  
...  
Keyword(s):  
National Park ◽  
Genome Mining ◽  
Gene Clusters ◽  
Microbial Interactions ◽  
Antimicrobial Compounds ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Molecular Networking ◽  
Peptide Synthetases ◽  
Genomic Basis

The marine bacterial genus Pseudoalteromonas is known for their ability to produce antimicrobial compounds. The metabolite-producing capacity of Pseudoalteromonas has been associated with strain pigmentation; however, the genomic basis of their antimicrobial capacity remains to be explained. In this study, we sequenced the whole genome of six Pseudoalteromonas strains (three pigmented and three non-pigmented), with the purpose of identifying biosynthetic gene clusters (BGCs) associated to compounds we detected via microbial interactions along through MS-based molecular networking. The genomes were assembled and annotated using the SPAdes and RAST pipelines and mined for the identification of gene clusters involved in secondary metabolism using the antiSMASH database. Nineteen BGCs were detected for each non-pigmented strain, while more than thirty BGCs were found for two of the pigmented strains. Among these, the groups of genes of nonribosomal peptide synthetases (NRPS) that code for bromoalterochromides stand out the most. Our results show that all strains possess BGCs for the production of secondary metabolites, and a considerable number of distinct polyketide synthases (PKS) and NRPS clusters are present in pigmented strains. Furthermore, the molecular networking analyses revealed two new molecules produced during microbial interactions: the dibromoalterochromides D/D’ (11–12).

scholarly journals Mining and unearthing hidden biosynthetic potential

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kirstin Scherlach ◽  
Christian Hertweck
Keyword(s):  
Small Molecules ◽  
Genome Mining ◽  
Gene Clusters ◽  
Ecological Interactions ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Metabolic Potential ◽  
Analytical Tools ◽  
Drug Leads ◽  
Chemical Mediators

AbstractGenetically encoded small molecules (secondary metabolites) play eminent roles in ecological interactions, as pathogenicity factors and as drug leads. Yet, these chemical mediators often evade detection, and the discovery of novel entities is hampered by low production and high rediscovery rates. These limitations may be addressed by genome mining for biosynthetic gene clusters, thereby unveiling cryptic metabolic potential. The development of sophisticated data mining methods and genetic and analytical tools has enabled the discovery of an impressive array of previously overlooked natural products. This review shows the newest developments in the field, highlighting compound discovery from unconventional sources and microbiomes.

scholarly journals luxRHomolog-Linked Biosynthetic Gene Clusters inProteobacteria

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Carolyn A. Brotherton ◽  
Marnix H. Medema ◽  
E. Peter Greenberg
Keyword(s):  
Genome Mining ◽  
Gene Clusters ◽  
Growth Conditions ◽  
Bioactive Metabolites ◽  
Growth Media ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Specialized Metabolites ◽  
A Genome ◽  
Functionally Diverse

ABSTRACTMicrobes are a major source of antibiotics, pharmaceuticals, and other bioactive compounds. The production of many specialized microbial metabolites is encoded in biosynthetic gene clusters (BGCs). A challenge associated with natural product discovery is that many BGCs are not expressed under laboratory growth conditions. Here we report a genome-mining approach to discover BGCs withluxR-type quorum sensing (QS) genes, which code for regulatory proteins that control gene expression. Our results show that BGCs linked to genes coding for LuxR-like proteins are widespread inProteobacteria. In addition, we show that associations betweenluxRhomolog genes and BGCs have evolved independently many times, with functionally diverse gene clusters. Overall, these clusters may provide a source of new natural products for which there is some understanding about how to elicit production.IMPORTANCEBacteria biosynthesize specialized metabolites with a variety of ecological functions, including defense against other microbes. Genes that code for specialized metabolite biosynthetic enzymes are frequently clustered together. These BGCs are often regulated by a transcription factor encoded within the cluster itself. These pathway-specific regulators respond to a signal or indirectly through other means of environmental sensing. Many specialized metabolites are not produced under laboratory growth conditions, and one reason for this issue is that laboratory growth media lack environmental cues necessary for BGC expression. Here, we report a bioinformatics study that reveals that BGCs are frequently linked to genes coding for LuxR family QS-responsive transcription factors in the phylumProteobacteria. The products of theseluxRhomolog-associated gene clusters may serve as a practical source of bioactive metabolites.

scholarly journals Draft Genome Sequence of Enterococcus durans OSY-EGY, a Multiple-Antimicrobial-Peptide Producer Isolated from Egyptian Hard Cheese

2019 ◽  
Vol 8 (28) ◽  
Author(s):  
Walaa E. Hussein ◽  
Lingzi Xiaoli ◽  
Ahmed E. Yousef
Keyword(s):  
Genome Sequence ◽  
Antimicrobial Agents ◽  
Draft Genome ◽  
Genome Mining ◽  
Gene Clusters ◽  
Draft Genome Sequence ◽  
Biosynthetic Gene Clusters ◽  
Content Type ◽  
Enterococcus Durans ◽  
A Genome

Enterococcus durans OSY-EGY was isolated recently from cheese. The strain produces potent antimicrobial agents. Here, we present the draft genome sequence of the strain, with a genome size of 3,230,625 bp and an average G+C content of 37.69%. Draft genome mining identified several biosynthetic gene clusters encoding multiple antimicrobial peptides.

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