scholarly journals Global biogeographic sampling of bacterial secondary metabolism

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Zachary Charlop-Powers ◽  
Jeremy G Owen ◽  
Boojala Vijay B Reddy ◽  
Melinda A Ternei ◽  
Denise O Guimarães ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Genome Sequencing ◽  
Geographic Distance ◽  
Gene Clusters ◽  
Natural World ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Road Map ◽  
Two Factors ◽  
Natural Products Discovery

Recent bacterial (meta)genome sequencing efforts suggest the existence of an enormous untapped reservoir of natural-product-encoding biosynthetic gene clusters in the environment. Here we use the pyro-sequencing of PCR amplicons derived from both nonribosomal peptide adenylation domains and polyketide ketosynthase domains to compare biosynthetic diversity in soil microbiomes from around the globe. We see large differences in domain populations from all except the most proximal and biome-similar samples, suggesting that most microbiomes will encode largely distinct collections of bacterial secondary metabolites. Our data indicate a correlation between two factors, geographic distance and biome-type, and the biosynthetic diversity found in soil environments. By assigning reads to known gene clusters we identify hotspots of biomedically relevant biosynthetic diversity. These observations not only provide new insights into the natural world, they also provide a road map for guiding future natural products discovery efforts.

scholarly journals Tapping Into Actinobacterial Genomes for Natural Product Discovery

2021 ◽  
Vol 12 ◽  
Author(s):  
Tanim Arpit Singh ◽  
Ajit Kumar Passari ◽  
Anjana Jajoo ◽  
Sheetal Bhasin ◽  
Vijai Kumar Gupta ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Genome Sequencing ◽  
Genetic Regulation ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Genomic Approach ◽  
New Gateway

The presence of secondary metabolite biosynthetic gene clusters (BGCs) makes actinobacteria well-known producers of diverse metabolites. These ubiquitous microbes are extensively exploited for their ability to synthesize diverse secondary metabolites. The extent of their ability to synthesize various molecules is yet to be evaluated. Current advancements in genome sequencing, metabolomics, and bioinformatics have provided a plethora of information about the mechanism of synthesis of these bioactive molecules. Accessing the biosynthetic gene cluster responsible for the production of metabolites has always been a challenging assignment. The genomic approach developments have opened a new gateway for examining and manipulating novel antibiotic gene clusters. These advancements have now developed a better understanding of actinobacterial physiology and their genetic regulation for the prolific production of natural products. These new approaches provide a unique opportunity to discover novel bioactive compounds that might replenish antibiotics’ exhausted stock and counter the microbes’ resistance crisis.

scholarly journals Secondary metabolites from hypocrealean entomopathogenic fungi: genomics as a tool to elucidate the encoded parvome

2020 ◽  
Vol 37 (9) ◽  
pp. 1164-1180 ◽  
Author(s):  
Liwen Zhang ◽  
Qun Yue ◽  
Chen Wang ◽  
Yuquan Xu ◽  
István Molnár
Keyword(s):  
Secondary Metabolites ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Bioactive Compounds ◽  
Entomopathogenic Fungi ◽  
Gene Clusters ◽  
Whole Genome ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters

Whole genome sequencing allows the cataloguing of the parvome (secondary metabolome) of hypocrealean entomopathogenic fungi, uncovering biosynthetic gene clusters for known and novel bioactive compounds with ecological and pharmaceutical significance.

scholarly journals Resistance Gene-Directed Genome Mining of 50 Aspergillus species

2018 ◽  
Author(s):  
Inge Kjærbølling ◽  
Tammi Vesth ◽  
Mikael R. Andersen
Keyword(s):  
Secondary Metabolites ◽  
Resistance Gene ◽  
Genome Sequencing ◽  
Genome Mining ◽  
Gene Clusters ◽  
Rational Approach ◽  
Whole Genome ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Valuable Compounds

AbstractFungal secondary metabolites are a rich source of valuable natural products. Genome sequencing have revealed an enormous potential from predicted biosynthetic gene clusters. It is however currently a time consuming task and an unfeasible task to characterize all biosynthetic gene cluster and to identify possible uses of the compounds. A rational approach is needed to identify promising gene clusters responsible for producing valuable compounds. Several valuable bioactive clusters have been shown to include a resistance gene which is a paralog of the target gene inhibited by the compound. This mechanism can be used to design a rational approach selecting those clusters.We have developed a pipeline FRIGG (Fungal Resistance Gene-directed Genome mining) identifying putative resistance genes found in biosynthetic gene clusters based on homology patterns of the cluster genes. The FRIGG pipeline has been run using 51 Aspergillus and Penicillium genomes, identifying 72 unique protein families with putative resistance genes using various settings in the pipeline. The pipeline was also able to identify the characterized resistance gene inpE from the Fellutamide B cluster thereby validating the approach.We have successfully developed an approach identifying putative valuable bio-active clusters based on a specific resistance mechanism. This approach will be highly useful as an ever increasing amount of genomic data becomes available — the art of identifying and selecting clusters producing novel valuable compounds will only become more crucial.ImportanceSpecies belonging to the Aspergillus genus are known to produce a large number of secondary metabolites, some of these compounds are bioactive and used as pharmaceuticals such as penicillin, cyclosporin and statin. With whole genome sequencing it became apparent that the genetic potential for secondary metabolite production is much bigger than expected. As an increasing number of species are whole genome sequenced an immense number of secondary metabolite genes are predicted and the question of how to selectively identify novel bioactive compounds from this information arises. To address this question, we have created a pipeline identifying genes likely involved in the production of bioactive compounds based on a resistance gene hypothesis approach.

scholarly journals Phytoplankton trigger the production of cryptic metabolites in the marine actinobacteria Salinispora tropica

2020 ◽  
Author(s):  
Audam Chhun ◽  
Despoina Sousoni ◽  
Maria del Mar Aguiló-Ferretjans ◽  
Lijiang Song ◽  
Christophe Corre ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Antibiotic Production ◽  
Antimicrobial Effect ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Marine Actinobacteria ◽  
Salinispora Tropica ◽  
Eukaryotic Phytoplankton

AbstractBacteria from the Actinomycete family are a remarkable source of natural products with pharmaceutical potential. The discovery of novel molecules from these organisms is, however, hindered because most of the biosynthetic gene clusters (BGCs) encoding these secondary metabolites are cryptic or silent and are referred to as orphan BGCs. While co-culture has proven to be a promising approach to unlock the biosynthetic potential of many microorganisms by activating the expression of these orphan BGCs, it still remains an underexplored technique. The marine actinobacteria Salinispora tropica, for instance, produces valuable compounds such as the anti-cancer molecule salinosporamide A but half of its putative BGCs are still orphan. Although previous studies have looked into using marine heterotrophs to induce orphan BGCs in Salinispora, the potential impact of co-culturing marine phototrophs with Salinispora has yet to be investigated. Following the observation of clear antimicrobial phenotype of the actinobacterium on a range of phytoplanktonic organisms, we here report the discovery of novel cryptic secondary metabolites produced by S. tropica in response to its co-culture with photosynthetic primary producers. An approach combining metabolomics and proteomics revealed that the photosynthate released by phytoplankton influences the biosynthetic capacities of S. tropica with both production of new molecules and the activation of orphan BGCs. Our work pioneers the use of phototrophs as a promising strategy to accelerate the discovery of novel natural products from actinobacteria.ImportanceThe alarming increase of antimicrobial resistance has generated an enormous interest in the discovery of novel active compounds. The isolation of new microbes to untap novel natural products is currently hampered because most biosynthetic gene clusters (BGC) encoded by these microorganisms are not expressed under standard laboratory conditions, i.e. mono-cultures. Here we show that co-culturing can be an easy way for triggering silent BGC. By combining state-of-the-art metabolomics and high-throughput proteomics, we characterized the activation of cryptic metabolites and silent biosynthetic gene clusters in the marine actinobacteria Salinispora tropica by the presence of phytoplankton photosynthate. We further suggest a mechanistic understanding of the antimicrobial effect this actinobacterium has on a broad range of prokaryotic and eukaryotic phytoplankton species and reveal a promising candidate for antibiotic production.

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.

scholarly journals IMG-ABC: A Knowledge Base To Fuel Discovery of Biosynthetic Gene Clusters and Novel Secondary Metabolites

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Michalis Hadjithomas ◽  
I-Min Amy Chen ◽  
Ken Chu ◽  
Anna Ratner ◽  
Krishna Palaniappan ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Genomic Data ◽  
Gene Clusters ◽  
Metagenomic Data ◽  
Integrated Analysis ◽  
Analysis Tool ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Analysis Tools

ABSTRACTIn the discovery of secondary metabolites, analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of computational platforms that enable such a systematic approach on a large scale. In this work, we present IMG-ABC (https://img.jgi.doe.gov/abc), an atlas of biosynthetic gene clusters within the Integrated Microbial Genomes (IMG) system, which is aimed at harnessing the power of “big” genomic data for discovering small molecules. IMG-ABC relies on IMG's comprehensive integrated structural and functional genomic data for the analysis of biosynthetic gene clusters (BCs) and associated secondary metabolites (SMs). SMs and BCs serve as the two main classes of objects in IMG-ABC, each with a rich collection of attributes. A unique feature of IMG-ABC is the incorporation of both experimentally validated and computationally predicted BCs in genomes as well as metagenomes, thus identifying BCs in uncultured populations and rare taxa. We demonstrate the strength of IMG-ABC's focused integrated analysis tools in enabling the exploration of microbial secondary metabolism on a global scale, through the discovery of phenazine-producing clusters for the first time inAlphaproteobacteria. IMG-ABC strives to fill the long-existent void of resources for computational exploration of the secondary metabolism universe; its underlying scalable framework enables traversal of uncovered phylogenetic and chemical structure space, serving as a doorway to a new era in the discovery of novel molecules.IMPORTANCEIMG-ABC is the largest publicly available database of predicted and experimental biosynthetic gene clusters and the secondary metabolites they produce. The system also includes powerful search and analysis tools that are integrated with IMG's extensive genomic/metagenomic data and analysis tool kits. As new research on biosynthetic gene clusters and secondary metabolites is published and more genomes are sequenced, IMG-ABC will continue to expand, with the goal of becoming an essential component of any bioinformatic exploration of the secondary metabolism world.

scholarly journals New Approaches to Detect Biosynthetic Gene Clusters in the Environment

Medicines ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 32 ◽  
Author(s):  
Ray Chen ◽  
Hon Wong ◽  
Brendan Burns
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Gene Clusters ◽  
Screening Methods ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Diverse Range ◽  
Bioinformatic Tools ◽  
Culture Independent ◽  
Traditional Approaches

Microorganisms in the environment can produce a diverse range of secondary metabolites (SM), which are also known as natural products. Bioactive SMs have been crucial in the development of antibiotics and can also act as useful compounds in the biotechnology industry. These natural products are encoded by an extensive range of biosynthetic gene clusters (BGCs). The developments in omics technologies and bioinformatic tools are contributing to a paradigm shift from traditional culturing and screening methods to bioinformatic tools and genomics to uncover BGCs that were previously unknown or transcriptionally silent. Natural product discovery using bioinformatics and omics workflow in the environment has demonstrated an extensive distribution of BGCs in various environments, such as soil, aquatic ecosystems and host microbiome environments. Computational tools provide a feasible and culture-independent route to find new secondary metabolites where traditional approaches cannot. This review will highlight some of the advances in the approaches, primarily bioinformatic, in identifying new BGCs, especially in environments where microorganisms are rarely cultured. This has allowed us to tap into the huge potential of microbial dark matter.

scholarly journals Draft Genome Sequence of Geobacillus sp. LEMMY01, a Thermophilic Bacterium Isolated from the Site of a Burning Grass Pile

2017 ◽  
Vol 5 (19) ◽  
Author(s):  
Yuri Pinheiro Alves de Souza ◽  
Fábio Faria da Mota ◽  
Alexandre Soares Rosado
Keyword(s):  
Secondary Metabolites ◽  
Genome Sequence ◽  
Draft Genome ◽  
Axenic Culture ◽  
Gene Clusters ◽  
Thermophilic Bacterium ◽  
Draft Genome Sequence ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Biotechnological Potential

ABSTRACT We report here the 3,586,065-bp draft genome of Geobacillus sp. LEMMY01, which was isolated (axenic culture) from a thermophilic chemolitoautotrophic consortium obtained from the site of a burning grass pile. The genome contains biosynthetic gene clusters coding for secondary metabolites, such as terpene and lantipeptide, confirming the biotechnological potential of this strain.

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