scholarly journals BioCAT: PSSM-based algorithm to search biosynthetic gene clusters producing nonribosomal peptides with known structure

2021 ◽  
Author(s):  
Dmitry N Konanov ◽  
Danil V Krivonos ◽  
Vladislav V Babenko ◽  
Elena N Ilina
Keyword(s):  
Chemical Structure ◽  
Gene Clusters ◽  
Nonribosomal Peptides ◽  
Biosynthetic Gene Clusters ◽  
High Priority Task ◽  
Peptide Synthetases ◽  
Priority Task ◽  
Modern Biotechnology ◽  
Bacteria And Fungi ◽  
Final Alignment

Motivation: Nonribosomal peptides (NRPs) are a class of secondary metabolites synthesized by multimodular enzymes named nonribosomal peptide synthetases (NRPSs) and mainly produced by bacteria and fungi. It has been shown that NRPs have a huge structural and functional diversity including antimicrobial activity, therefore, they are of increasing interest for modern biotechnology. Methods such as NMR and LC-MS/MS allow to determine NRP structure precisely, but it is often not a trivial task to find natural producers of them. Today, searches are usually performed manually, mostly with tools such as antiSMASH or Prism. However, there are cases when potential producers should be found among hundreds of strains, for instance, when analyzing metagenomes data. Thus, the development of automated approaches is a high-priority task for further NRP research. Results: We developed BioCAT, a two-side approach to find biosynthesys gene clusters (BGCs) which may produce a given NRP when the structure of interesting NRP has already been found. Formally, the BioCAT unites the antiSMASH software and the rBAN retrosynthesis tool but some improvements were added to both gene cluster and NRP chemical structure analyses. The main feature of the method is PSSM usage to store specificities of NRPS modules, which has increased the alignment quality in comparison with more strict approaches developed earlier. An ensemble model was implemented to calculate the final alignment score. We tested the method on a manually curated NRP producers database and compared it with a competing tool called GARLIC. Finally, we showed the method applicability on a several external examples.

BIOINFORMATIC ANALYSIS OF BIOSYNTHETIC GENE CLUSTERS OF NONRIBOSOMAL PEPTIDES IN BACTERIA BASED ON PREDICTION OF GENE TRANSLATION ELONGATION EFFICIENCY

2020 ◽  
pp. 262-265
Author(s):  
A. Klimenko ◽  
S. Lashin ◽  
D. Afonnikov
Keyword(s):  
Gene Clusters ◽  
Bioinformatic Analysis ◽  
Evolutionary Strategies ◽  
Nonribosomal Peptides ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Translation Elongation ◽  
Coding Sequences ◽  
Peptide Synthetases ◽  
Gene Coding

We have found out that those two classes of bacteria whose genomes contain and do not contain biosynthetic gene clusters of nonribosomal peptide synthetases substantially differentiate in preferred evolutionary strategies for optimizing primary structure of their gene coding sequences.

scholarly journals Detecting and prioritizing biosynthetic gene clusters for bioactive compounds in bacteria and fungi

2019 ◽  
Vol 103 (8) ◽  
pp. 3277-3287 ◽  
Author(s):  
Phuong Nguyen Tran ◽  
Ming-Ren Yen ◽  
Chen-Yu Chiang ◽  
Hsiao-Ching Lin ◽  
Pao-Yang Chen
Keyword(s):  
Bioactive Compounds ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Bacteria And Fungi

scholarly journals An Orphan MbtH-Like Protein Interacts with Multiple Nonribosomal Peptide Synthetases inMyxococcus xanthusDK1622

2018 ◽  
Vol 200 (21) ◽  
Author(s):  
Karla J. Esquilín-Lebrón ◽  
Tye O. Boynton ◽  
Lawrence J. Shimkets ◽  
Michael G. Thomas
Keyword(s):  
Myxococcus Xanthus ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Nonribosomal Peptide ◽  
Content Type ◽  
Nonribosomal Peptide Synthetases ◽  
Peptide Synthetases

ABSTRACTOne mechanism by which bacteria and fungi produce bioactive natural products is the use of nonribosomal peptide synthetases (NRPSs). Many NRPSs in bacteria require members of the MbtH-like protein (MLP) superfamily for their solubility or function. Although MLPs are known to interact with the adenylation domains of NRPSs, the role MLPs play in NRPS enzymology has yet to be elucidated. MLPs are nearly always encoded within the biosynthetic gene clusters (BGCs) that also code for the NRPSs that interact with the MLP. Here, we identify 50 orphan MLPs from diverse bacteria. An orphan MLP is one that is encoded by a gene that is not directly adjacent to genes predicted to be involved in nonribosomal peptide biosynthesis. We targeted the orphan MLP MXAN_3118 fromMyxococcus xanthusDK1622 for characterization. TheM. xanthusDK1622 genome contains 15 NRPS-encoding BGCs but only one MLP-encoding gene (MXAN_3118). We tested the hypothesis that MXAN_3118 interacts with one or more NRPS using a combination ofin vivoandin vitroassays. We determined that MXAN_3118 interacts with at least seven NRPSs from distinct BGCs. We show that one of these BGCs codes for NRPS enzymology that likely produces a valine-rich natural product that inhibits the clumping ofM. xanthusDK1622 in liquid culture. MXAN_3118 is the first MLP to be identified that naturally interacts with multiple NRPS systems in a single organism. The finding of an MLP that naturally interacts with multiple NRPS systems suggests it may be harnessed as a “universal” MLP for generating functional hybrid NRPSs.IMPORTANCEMbtH-like proteins (MLPs) are essential accessory proteins for the function of many nonribosomal peptide synthetases (NRPSs). We identified 50 MLPs from diverse bacteria that are coded by genes that are not located near any NRPS-encoding biosynthetic gene clusters (BGCs). We define these as orphan MLPs because their NRPS partner(s) is unknown. Investigations into the orphan MLP fromMyxococcus xanthusDK1622 determined that it interacts with NRPSs from at least seven distinct BGCs. Support for these MLP-NRPS interactions came from the use of a bacterial two-hybrid assay and copurification of the MLP with various NRPSs. The flexibility of this MLP to naturally interact with multiple NRPSs led us to hypothesize that this MLP may be used as a “universal” MLP during the construction of functional hybrid NRPSs.

scholarly journals Secondary metabolite biosynthetic diversity in Arctic Ocean metagenomes

2021 ◽  
Vol 7 (12) ◽  
Author(s):  
Adriana Rego ◽  
Antonio Fernandez-Guerra ◽  
Pedro Duarte ◽  
Philipp Assmy ◽  
Pedro N. Leão ◽  
...  
Keyword(s):  
Heterologous Expression ◽  
Arctic Ocean ◽  
High Throughput Sequencing ◽  
Large Fraction ◽  
Environmental Dna ◽  
Gene Clusters ◽  
Biosynthetic Gene Clusters ◽  
Bacterial Isolation ◽  
Biosynthetic Genes ◽  
Peptide Synthetases

Polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) are mega enzymes responsible for the biosynthesis of a large fraction of natural products (NPs). Molecular markers for biosynthetic genes, such as the ketosynthase (KS) domain of PKSs, have been used to assess the diversity and distribution of biosynthetic genes in complex microbial communities. More recently, metagenomic studies have complemented and enhanced this approach by allowing the recovery of complete biosynthetic gene clusters (BGCs) from environmental DNA. In this study, the distribution and diversity of biosynthetic genes and clusters from Arctic Ocean samples (NICE-2015 expedition), was assessed using PCR-based strategies coupled with high-throughput sequencing and metagenomic analysis. In total, 149 KS domain OTU sequences were recovered, 36 % of which could not be assigned to any known BGC. In addition, 74 bacterial metagenome-assembled genomes were recovered, from which 179 BGCs were extracted. A network analysis identified potential new NP families, including non-ribosomal peptides and polyketides. Complete or near-complete BGCs were recovered, which will enable future heterologous expression efforts to uncover the respective NPs. Our study represents the first report of biosynthetic diversity assessed for Arctic Ocean metagenomes and highlights the potential of Arctic Ocean planktonic microbiomes for the discovery of novel secondary metabolites. The strategy employed in this study will enable future bioprospection, by identifying promising samples for bacterial isolation efforts, while providing also full-length BGCs for heterologous expression.

scholarly journals Draft Genome Sequence of Streptomyces sp. Strain C8S0, Isolated from a Highly Oligotrophic Sediment

2020 ◽  
Vol 9 (14) ◽  
Author(s):  
S. Gallegos-Lopez ◽  
P. M. Mejia-Ponce ◽  
L. A. Gonzalez-Salazar ◽  
L. Rodriguez-Orduña ◽  
V. Souza-Saldivar ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Draft Genome ◽  
Gene Clusters ◽  
Draft Genome Sequence ◽  
Bioactive Metabolites ◽  
Nonribosomal Peptides ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Cuatro Ciénegas ◽  
Cuatro Ciénegas Basin

Streptomyces spp. are prolific bacteria producing bioactive metabolites. We present the draft genome sequence of Streptomyces sp. strain C8S0, which was isolated from a highly oligotrophic sediment from the Cuatro Cienegas Basin (Mexico). The whole-genome assembly comprised 6,898,902 bp, with 18 biosynthetic gene clusters, including those for nonconventional terpenes, nonribosomal peptides, and polyketides.

scholarly journals Genome Sequences of Serratia Strains Revealed Common Genes in Both Serratomolides Gene Clusters

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 482
Author(s):  
Catarina Marques-Pereira ◽  
Diogo Neves Proença ◽  
Paula V. Morais
Keyword(s):  
Comparative Genomics ◽  
Gene Cluster ◽  
Genomic Analysis ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Genome Sequences ◽  
Biosynthetic Gene Clusters ◽  
Bacteria And Fungi ◽  
Different Strains ◽  
First Time

Serratia strains are ubiquitous microorganisms with the ability to produce serratomolides, such as serrawettins. These extracellular lipopeptides are described as biocides against many bacteria and fungi and may have a nematicidal activity against phytopathogenic nematodes. Serrawettins W1 and W2 from different strains have different structures that might be correlated with distinct genomic organizations. This work used comparative genomics to determine the distribution and the organization of the serrawettins biosynthetic gene clusters in all the 84 publicly available genomes of the Serratia genus. The serrawettin W1 and W2 gene clusters’ organization was established using antiSMASH software and compared with single and short data previously described for YD25TSerratia. Here, the serrawettin W1 gene clusters’ organization is reported for the first time. The serrawettin W1 biosynthetic gene swrW was present in 17 Serratia genomes. Eighty different coding sequence (CDS) were assigned to the W1 gene cluster, 13 being common to all clusters. The serrawettin W2 swrA gene was present in 11 Serratia genomes. The W2 gene clusters included 68 CDS with 24 present in all the clusters. The genomic analysis showed the swrA gene constitutes five modules, four with three domains and one with four domains, while the swrW gene constitutes one module with four domains. This work identified four genes common to all serrawettin gene clusters, highlighting their essential potential in the serrawettins biosynthetic process.

scholarly journals Endophytic microbes from Nigerian ethnomedicinal plants: a potential source for bioactive secondary metabolites—a review

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Chijioke E. Ezeobiora ◽  
Nwamaka H. Igbokwe ◽  
Dina H. Amin ◽  
Udoma E. Mendie
Keyword(s):  
Infectious Diseases ◽  
Anticancer Agents ◽  
Gene Clusters ◽  
Emerging Diseases ◽  
Bioactive Molecules ◽  
Main Body ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Ethnomedicinal Plants ◽  
Bacteria And Fungi

Abstract Background Endophytes are highly beneficial species of microbes that live in symbiosis with plant tissues in the setting. Endophytes are difficult to isolate in their natural environment, and they are understudied despite being a rich source of bioactive molecules. There are varieties of new infectious diseases emerging across the world, necessitating a constant and expanded search for newer and more efficient bioactive molecules. Nigeria is known for its biodiversity in ethnomedicinal plants, yet these plants are understudied for endophytic microbes harbouring novel bioactive molecules. Main body Endophytes are a source of novel organic natural molecules and are thought to be drug discovery frontiers. Endophyte research has contributed to the discovery of possible anticancer agents following the discovery of taxol. Endophyte research has contributed to the discovery of possible drug compounds with antimicrobial, antioxidant, antiviral, antidiabetic, anti-Alzheimers disease and immunosuppressive properties among others. These breakthroughs provide hope for combating incurable diseases, drug resistance, the emergence of new infectious diseases, and other human health issues. Finding new medicines that may be effective candidates for treating newly emerging diseases in humans has a lot of promise. Most studies have been on fungi endophytes, with just a few reports on bacterial endophytes. The biology of endophytic bacteria and fungi, as well as endophytic microbes isolated from Nigerian medicinal plants, their isolation methods, identification by morphological and molecular methods, fermentation, purification, identification of bioactive compounds and biosynthetic gene clusters are all covered in this study. Conclusion In Nigeria, the sourcing and isolation of endophytes harboring biosynthetic gene clusters are still understudied, necessitating a rigorous quest for bioactive molecules in endophytes inhabiting various ethnomedicinal plants.

scholarly journals Discovery and Heterologous Production of New Cyclic Depsibosamycins

2021 ◽  
Vol 9 (7) ◽  
pp. 1396
Author(s):  
Marc Stierhof ◽  
Maksym Myronovskyi ◽  
Josef Zapp ◽  
Andriy Luzhetskyy
Keyword(s):  
Cyclic Peptides ◽  
Gene Clusters ◽  
Combinatorial Biosynthesis ◽  
Side Chain ◽  
Biological Functions ◽  
Biosynthetic Gene Clusters ◽  
Streptomyces Species ◽  
Peptide Synthetases ◽  
Major Interest ◽  
In Silico Identification

Streptomyces are producers of valuable secondary metabolites with unique scaffolds that perform a plethora of biological functions. Nonribosomal peptides are of special interest due to their variety and complexity. They are synthesized by nonribosomal peptide synthetases, large biosynthetic machineries that are encoded in the genome of many Streptomyces species. The identification of new peptides and the corresponding biosynthetic gene clusters is of major interest since knowledge can be used to facilitate combinatorial biosynthesis and chemical semisynthesis of natural products. The recently discovered bosamycins are linear octapeptides with an interesting 5-OMe tyrosine moiety and various modifications at the N-terminus. In this study, the new cyclic depsibosamycins B, C, and D from Streptomyces aurantiacus LU19075 were discovered. In comparison to the linear bosamycins B, C, and D, which were also produced by the strain, the cyclic depsibosamycins showed a side-chain-to-tail lactonization of serine and glycine, leading to a ring of four amino acids. In silico identification and heterologous expression of the depsibosamycin (dbm) gene cluster indicated that the cyclic peptides, rather than the linear derivatives, are the main products of the cluster.

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).

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