scholarly journals Activation of Secondary Metabolite Gene Clusters in Streptomyces clavuligerus by the PimM Regulator of Streptomyces natalensis

2019 ◽  
Vol 10 ◽  
Author(s):  
Yolanda Martínez-Burgo ◽  
Javier Santos-Aberturas ◽  
Antonio Rodríguez-García ◽  
Eva G. Barreales ◽  
José Rubén Tormo ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Gene Clusters ◽  
Streptomyces Clavuligerus ◽  
Streptomyces Natalensis

scholarly journals Elucidating the Regulatory Elements for Transcription Termination and Posttranscriptional Processing in the Streptomyces clavuligerus Genome

mSystems ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Soonkyu Hwang ◽  
Namil Lee ◽  
Donghui Choe ◽  
Yongjae Lee ◽  
Woori Kim ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Transcription Termination ◽  
Gene Clusters ◽  
Streptomyces Clavuligerus ◽  
Regulatory Elements ◽  
Regulation Of Transcription ◽  
Content Type ◽  
Transcriptional Regulatory Elements ◽  
Transcriptional Regulatory ◽  
Posttranscriptional Processing

ABSTRACT Identification of transcriptional regulatory elements in the GC-rich Streptomyces genome is essential for the production of novel biochemicals from secondary metabolite biosynthetic gene clusters (smBGCs). Despite many efforts to understand the regulation of transcription initiation in smBGCs, information on the regulation of transcription termination and posttranscriptional processing remains scarce. In this study, we identified the transcriptional regulatory elements in β-lactam antibiotic-producing Streptomyces clavuligerus ATCC 27064 by determining a total of 1,427 transcript 3′-end positions (TEPs) using the term-seq method. Termination of transcription was governed by three classes of TEPs, of which each displayed unique sequence features. The data integration with transcription start sites and transcriptome data generated 1,648 transcription units (TUs) and 610 transcription unit clusters (TUCs). TU architecture showed that the transcript abundance in TU isoforms of a TUC was potentially affected by the sequence context of their TEPs, suggesting that the regulatory elements of TEPs could control the transcription level in additional layers. We also identified TU features of a xenobiotic response element (XRE) family regulator and DUF397 domain-containing protein, particularly showing the abundance of bidirectional TEPs. Finally, we found that 189 noncoding TUs contained potential cis- and trans-regulatory elements that played a major role in regulating the 5′ and 3′ UTR. These findings highlight the role of transcriptional regulatory elements in transcription termination and posttranscriptional processing in Streptomyces sp. IMPORTANCE Streptomyces sp. is a great source of bioactive secondary metabolites, including antibiotics, antifungal agents, antiparasitic agents, immunosuppressant compounds, and other drugs. Secondary metabolites are synthesized via multistep conversions of the precursor molecules from primary metabolism, governed by multicomplex enzymes from secondary metabolite biosynthetic gene clusters. As their production is closely related with the growth phase and dynamic cellular status in response to various intra- and extracellular signals, complex regulatory systems tightly control the gene expressions related to secondary metabolism. In this study, we determined genome-wide transcript 3′-end positions and transcription units in the β-lactam antibiotic producer Streptomyces clavuligerus ATCC 27064 to elucidate the transcriptional regulatory elements in transcription termination and posttranscriptional processing by integration of multiomics data. These unique features, such as transcript 3′-end sequence, potential riboregulators, and potential 3′-untranslated region (UTR) cis-regulatory elements, can be potentially used to design engineering tools that can regulate the transcript abundance of genes for enhancing secondary metabolite production.

Genome sequence of Novosphingobium malaysiense strain MUSC 273T, novel alpha-proteobacterium isolated from intertidal soil

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Hooi-Leng Ser ◽  
Wai-Fong Yin ◽  
Kok-Gan Chan ◽  
Nurul-Syakima Ab Mutalib ◽  
Learn-Han Lee
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Genome Sequence ◽  
Catalase Activity ◽  
Gene Clusters ◽  
Rrna Genes ◽  
Gram Negative ◽  
Genomic Features

Novosphingobium malaysiense strain MUSC 273T is a recently identified Gram-negative, aerobic alpha-proteobacterium. The strain was isolated from intertidal soil with strong catalase activity. The genome sequence comprises 5,027,021 bp, with 50 tRNA and 3 rRNA genes. Further analysis identified presence of secondary metabolite gene clusters within genome of MUSC 273T. Knowledge of the genomic features of the strain may allow further biotechnological exploitation, particularly for production of secondary metabolites as well as production of industrially important enzymes

scholarly journals Specialized Metabolites from Ribosome Engineered Strains of Streptomyces clavuligerus

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 239
Author(s):  
Arshad Ali Shaikh ◽  
Louis-Felix Nothias ◽  
Santosh K. Srivastava ◽  
Pieter C. Dorrestein ◽  
Kapil Tahlan
Keyword(s):  
In Silico Analysis ◽  
Cost Effective ◽  
Gene Clusters ◽  
Streptomyces Clavuligerus ◽  
Strain Engineering ◽  
Ribosome Recycling Factor ◽  
Metabolic Potential ◽  
Putative Gene ◽  
Specialized Metabolites ◽  
Streptomyces Spp

Bacterial specialized metabolites are of immense importance because of their medicinal, industrial, and agricultural applications. Streptomyces clavuligerus is a known producer of such compounds; however, much of its metabolic potential remains unknown, as many associated biosynthetic gene clusters are silent or expressed at low levels. The overexpression of ribosome recycling factor (frr) and ribosome engineering (induced rpsL mutations) in other Streptomyces spp. has been reported to increase the production of known specialized metabolites. Therefore, we used an overexpression strategy in combination with untargeted metabolomics, molecular networking, and in silico analysis to annotate 28 metabolites in the current study, which have not been reported previously in S. clavuligerus. Many of the newly described metabolites are commonly found in plants, further alluding to the ability of S. clavuligerus to produce such compounds under specific conditions. In addition, the manipulation of frr and rpsL led to different metabolite production profiles in most cases. Known and putative gene clusters associated with the production of the observed compounds are also discussed. This work suggests that the combination of traditional strain engineering and recently developed metabolomics technologies together can provide rapid and cost-effective strategies to further speed up the discovery of novel natural products.

Identification of the kinanthraquinone biosynthetic gene cluster by expression of an atypical response regulator

2021 ◽  
Vol 85 (3) ◽  
pp. 714-721
Author(s):  
Risa Takao ◽  
Katsuyuki Sakai ◽  
Hiroyuki Koshino ◽  
Hiroyuki Osada ◽  
Shunji Takahashi
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Secondary Metabolite ◽  
Response Regulator ◽  
Bac Library ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Gene Organization ◽  
Biosynthetic Gene ◽  
Streptomyces Sp

ABSTRACT Recent advances in genome sequencing have revealed a variety of secondary metabolite biosynthetic gene clusters in actinomycetes. Understanding the biosynthetic mechanism controlling secondary metabolite production is important for utilizing these gene clusters. In this study, we focused on the kinanthraquinone biosynthetic gene cluster, which has not been identified yet in Streptomyces sp. SN-593. Based on chemical structure, 5 type II polyketide synthase gene clusters were listed from the genome sequence of Streptomyces sp. SN-593. Among them, a candidate gene cluster was selected by comparing the gene organization with grincamycin, which is synthesized through an intermediate similar to kinanthraquinone. We initially utilized a BAC library for subcloning the kiq gene cluster, performed heterologous expression in Streptomyces lividans TK23, and identified the production of kinanthraquinone and kinanthraquinone B. We also found that heterologous expression of kiqA, which belongs to the DNA-binding response regulator OmpR family, dramatically enhanced the production of kinanthraquinones.

scholarly journals Draft Genome Sequences of Fungus Aspergillus calidoustus

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Fabian Horn ◽  
Jörg Linde ◽  
Derek J. Mattern ◽  
Grit Walther ◽  
Reinhard Guthke ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Genome Sequence ◽  
Functional Annotation ◽  
Draft Genome ◽  
Genome Mining ◽  
Gene Clusters ◽  
Draft Genome Sequence ◽  
Genome Sequences

Here, we report the draft genome sequence of Aspergillus calidoustus (strain SF006504) . The functional annotation of A. calidoustus predicts a relatively large number of secondary metabolite gene clusters. The presented genome sequence builds the basis for further genome mining.

An atlas of bacterial secondary metabolite biosynthesis gene clusters

2021 ◽  
Author(s):  
Bin Wei ◽  
Ao‐Qi Du ◽  
Zhen‐Yi Zhou ◽  
Cong Lai ◽  
Wen‐Chao Yu ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Gene Clusters ◽  
Biosynthesis Gene ◽  
Secondary Metabolite Biosynthesis

scholarly journals Vibrio gazogenes inhibits aflatoxin production through downregulation of aflatoxin biosynthetic genes in Aspergillus flavus

2022 ◽  
Author(s):  
Shyam L. Kandel ◽  
Rubaiya Jesmin ◽  
Brian M. Mack ◽  
Rajtilak Majumdar ◽  
Matthew K. Gilbert ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Aspergillus Flavus ◽  
Fungal Biomass ◽  
Expression Profiles ◽  
Health Hazard ◽  
Gene Clusters ◽  
Aflatoxin Contamination ◽  
Aflatoxin Biosynthesis ◽  
Control Samples

Aspergillus flavus is an opportunistic pathogen of oilseed crops such as maize, peanut, cottonseed, and tree nuts and produces carcinogenic secondary metabolites known as aflatoxins during seed colonization. Aflatoxin contamination not only reduces the value of the produce but also is a health hazard to humans and animals. Previously, we observed inhibition of A. flavus aflatoxin biosynthesis upon exposure to the marine bacterium, Vibrio gazogenes (Vg). In this study, we used RNA sequencing to examine the transcriptional profiles of A. flavus treated with both live and heat-inactivated dead Vg and control samples. Fungal biomass, total accumulated aflatoxins, and expression profiles of genes constituting secondary metabolite biosynthetic gene clusters were determined at 24, 30, and 40 h after treatment. Statistically significant reductions in total aflatoxins were detected in Vg-treated samples as compared to control samples at 40 h. But no statistical difference in fungal biomass was observed upon these treatments. The Vg treatments were most effective on aflatoxin biosynthesis as was reflected in significant downregulation of majority of the genes in the aflatoxin gene cluster including the aflatoxin pathway regulator gene, aflR. Along with aflatoxin genes, we also observed significant downregulation in some other secondary metabolite gene clusters including cyclopiazonic acid and aflavarin, suggesting that the treatment may inhibit other secondary metabolites as well. Finally, a weighted gene correlation network analysis identified an upregulation of ten genes that were most strongly associated with Vg-dependent aflatoxin inhibition and provide a novel start-point in understanding the mechanisms that result in this phenomenon.

scholarly journals Phylogenetic Distribution of Secondary Metabolites in the Bacillus subtilis Species Complex

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Kat Steinke ◽  
Omkar S. Mohite ◽  
Tilmann Weber ◽  
Ákos T. Kovács
Keyword(s):  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Species Complex ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Content Type ◽  
Frameshift Mutations ◽  
Metabolite Production

ABSTRACT Microbes produce a plethora of secondary (or specialized) metabolites that, although not essential for primary metabolism, benefit them to survive in the environment, communicate, and influence cell differentiation. Biosynthetic gene clusters (BGCs), responsible for the production of these secondary metabolites, are readily identifiable on bacterial genome sequences. Understanding the phylogeny and distribution of BGCs helps us to predict the natural product synthesis ability of new isolates. Here, we examined 310 genomes from the Bacillus subtilis group, determined the inter- and intraspecies patterns of absence/presence for all BGCs, and assigned them to defined gene cluster families (GCFs). This allowed us to establish patterns in the distribution of both known and unknown products. Further, we analyzed variations in the BGC structures of particular families encoding natural products, such as plipastatin, fengycin, iturin, mycosubtilin, and bacillomycin. Our detailed analysis revealed multiple GCFs that are species or clade specific and a few others that are scattered within or between species, which will guide exploration of the chemodiversity within the B. subtilis group. Surprisingly, we discovered that partial deletion of BGCs and frameshift mutations in selected biosynthetic genes are conserved within phylogenetically related isolates, although isolated from around the globe. Our results highlight the importance of detailed genomic analysis of BGCs and the remarkable phylogenetically conserved erosion of secondary metabolite biosynthetic potential in the B. subtilis group. IMPORTANCE Members of the B. subtilis species complex are commonly recognized producers of secondary metabolites, among those, the production of antifungals, which makes them promising biocontrol strains. While there are studies examining the distribution of well-known secondary metabolites in Bacilli, intraspecies clade-specific distribution has not been systematically reported for the B. subtilis group. Here, we report the complete biosynthetic potential within the B. subtilis group to explore the distribution of the biosynthetic gene clusters and to reveal an exhaustive phylogenetic conservation of secondary metabolite production within Bacillus that supports the chemodiversity within this species complex. We identify that certain gene clusters acquired deletions of genes and particular frameshift mutations, rendering them inactive for secondary metabolite biosynthesis, a conserved genetic trait within phylogenetically conserved clades of certain species. The overview guides the assignment of the secondary metabolite production potential of newly isolated Bacillus strains based on genome sequence and phylogenetic relatedness.

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