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 Modular and Integrative Vectors for Synthetic Biology Applications in Streptomyces spp.

2019 ◽  
Vol 85 (16) ◽  
Author(s):  
Céline Aubry ◽  
Jean-Luc Pernodet ◽  
Sylvie Lautru
Keyword(s):  
Synthetic Biology ◽  
Anticancer Agents ◽  
Gene Clusters ◽  
Bioactive Molecules ◽  
Dna Assembly ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Dna Cloning ◽  
Specialized Metabolism ◽  
Assembly Method

ABSTRACT With the development of synthetic biology in the field of (actinobacterial) specialized metabolism, new tools are needed for the design or refactoring of biosynthetic gene clusters. If libraries of synthetic parts (such as promoters or ribosome binding sites) and DNA cloning methods have been developed, to our knowledge, not many vectors designed for the flexible cloning of biosynthetic gene clusters have been constructed. We report here the construction of a set of 12 standardized and modular vectors designed to afford the construction or the refactoring of biosynthetic gene clusters in Streptomyces species, using a large panel of cloning methods. Three different resistance cassettes and four orthogonal integration systems are proposed. In addition, FLP recombination target sites were incorporated to allow the recycling of antibiotic markers and to limit the risks of unwanted homologous recombination in Streptomyces strains when several vectors are used. The functionality and proper integration of the vectors in three commonly used Streptomyces strains, as well as the functionality of the Flp-catalyzed excision, were all confirmed. To illustrate some possible uses of our vectors, we refactored the albonoursin gene cluster from Streptomyces noursei using the BioBrick assembly method. We also used the seamless ligase chain reaction cloning method to assemble a transcription unit in one of the vectors and genetically complement a mutant strain. IMPORTANCE One of the strategies employed today to obtain new bioactive molecules with potential applications for human health (for example, antimicrobial or anticancer agents) is synthetic biology. Synthetic biology is used to biosynthesize new unnatural specialized metabolites or to force the expression of otherwise silent natural biosynthetic gene clusters. To assist the development of synthetic biology in the field of specialized metabolism, we constructed and are offering to the community a set of vectors that were intended to facilitate DNA assembly and integration in actinobacterial chromosomes. These vectors are compatible with various DNA cloning and assembling methods. They are standardized and modular, allowing the easy exchange of a module by another one of the same nature. Although designed for the assembly or the refactoring of specialized metabolite gene clusters, they have a broader potential utility, for example, for protein production or genetic complementation.

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 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 Microbiological and molecular insights on rare Actinobacteria harboring bioactive prospective

2020 ◽  
Vol 44 (1) ◽  
Author(s):  
Dina H. Amin ◽  
Nagwa A. Abdallah ◽  
Assem Abolmaaty ◽  
Sahar Tolba ◽  
Elizabeth M. H. Wellington
Keyword(s):  
Bioinformatics Analysis ◽  
Genetic Manipulation ◽  
Antibiotic Production ◽  
Gene Clusters ◽  
Bioactive Molecules ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Pcr Screening ◽  
Molecular Approaches ◽  
Shed Light

Abstract Background Actinobacteria is as a group of advanced filamentous bacteria. Rare Actinobacteria are of special interest as they are rarely isolated from the environments. They are a major source of important bioactive compounds. Determining the proper strategy for the identification of Actinobacteria harboring biosynthetic gene clusters and producing bioactive molecules is a challenging platform. Methodology In this review, we discuss a consequence of microbiological and molecular methods for the identification of rare Actinobacteria. In addition to that, we shed light on rare Actinobacteria’s significance in antibiotic production. We also clarified molecular approaches for the manipulation of novel biosynthetic gene clusters via PCR screening, fosmid libraries, and Illumina whole-genome sequencing in combination with bioinformatics analysis. Conclusion Perceptions of the conventional and molecular identification of Actinobacteria were conducted. This will open the door for the genetic manipulation of novel antibiotic gene clusters in heterologous hosts. Also, these conclusions will lead to constructing new bioactive molecules via genetically engineering biosynthetic pathways.

scholarly journals A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Loïc Martinet ◽  
Aymeric Naômé ◽  
Benoit Deflandre ◽  
Marta Maciejewska ◽  
Déborah Tellatin ◽  
...  
Keyword(s):  
Natural Product ◽  
Gene Cluster ◽  
Biosynthetic Pathway ◽  
Genome Mining ◽  
Gene Clusters ◽  
Bioactive Molecules ◽  
Bioactive Metabolites ◽  
Biosynthetic Gene ◽  
Single Family ◽  
Biosynthetic Gene Clusters

ABSTRACT Biosynthetic gene clusters (BGCs) are organized groups of genes involved in the production of specialized metabolites. Typically, one BGC is responsible for the production of one or several similar compounds with bioactivities that usually only vary in terms of strength and/or specificity. Here we show that the previously described ferroverdins and bagremycins, which are families of metabolites with different bioactivities, are produced from the same BGC, whereby the fate of the biosynthetic pathway depends on iron availability. Under conditions of iron depletion, the monomeric bagremycins are formed, representing amino-aromatic antibiotics resulting from the condensation of 3-amino-4-hydroxybenzoic acid with p-vinylphenol. Conversely, when iron is abundantly available, the biosynthetic pathway additionally produces a molecule based on p-vinylphenyl-3-nitroso-4-hydroxybenzoate, which complexes iron to form the trimeric ferroverdins that have anticholesterol activity. Thus, our work shows a unique exception to the concept that BGCs should only produce a single family of molecules with one type of bioactivity and that in fact different bioactive molecules may be produced depending on the environmental conditions. IMPORTANCE Access to whole-genome sequences has exposed the general incidence of the so-called cryptic biosynthetic gene clusters (BGCs), thereby renewing their interest for natural product discovery. As a consequence, genome mining is the often first approach implemented to assess the potential of a microorganism for producing novel bioactive metabolites. By revealing a new level of complexity of natural product biosynthesis, we further illustrate the difficulty of estimation of the panel of molecules associated with a BGC based on genomic information alone. Indeed, we found that the same gene cluster is responsible for the production of compounds which differ in terms of structure and bioactivity. The production of these different compounds responds to different environmental triggers, which suggests that multiplication of culture conditions is essential for revealing the entire panel of molecules made by a single BGC.

scholarly journals Characterisation of anti-pseudomonad activity of hyper-arid Micromonospora species

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
David Mark ◽  
Jan DeWald ◽  
Cristina Dorador ◽  
Nicholas Tucker ◽  
Paul Herron
Keyword(s):  
Aminoglycoside Antibiotic ◽  
Gene Clusters ◽  
Opportunistic Pathogen ◽  
World Health Organisation ◽  
Resistance Mechanisms ◽  
Bioactive Molecules ◽  
World Health ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Novel Antibiotics

The opportunistic pathogen Pseudomonas aeruginosa is a major cause of nosocomial infections, and has been categorised by the World Health Organisation as a “Priority 1: Critical” target for research and development of novel antibiotics owing to its intrinsic multi-resistance and ability to acquire novel resistance mechanisms. One strategy for discovering novel antibiotics is the identification and characterisation of metabolites with antimicrobial activity. Members of the bacterial phylum Actinobacteria are historic source of these metabolites, in particular the genus Streptomyces. However, other genera have not received this same level of interest despite sharing the capacity to biosynthesise a diverse array of metabolites. One such genus is Micromonospora, responsible for production of the broad-spectrum aminoglycoside antibiotic gentamicin (M. purpurea). Here we present three Micromonospora species isolated from the Atacama Desert, Chile; that possess anti-pseudomonad bioactivity inducible by culture on International Streptomyces Project (ISP) Media. In addition, preliminary data indicates that this activity can be affected by the addition of P. aeruginosa conditioned media. In parallel, short-read Illumina sequencing was used to assemble draft genomes for these strains, enabling antiSMASH analysis of putative biosynthetic gene clusters. In addition to this, estimated Average Nucleotide Identity (ANI) as calculated by the autoMLST server indicates that these strains may all be novel Micromonospora species. The results of this work serve to highlight the biosynthetic capacity of an understudied genus of bacteria, as well as the value of examining underexplored environments and habitats in the search for novel bioactive molecules.

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 Microfluidic automated plasmid library enrichment for biosynthetic gene cluster discovery

2020 ◽  
Vol 48 (8) ◽  
pp. e48-e48 ◽  
Author(s):  
Peng Xu ◽  
Cyrus Modavi ◽  
Benjamin Demaree ◽  
Frederick Twigg ◽  
Benjamin Liang ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Type I ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Plasmid Library ◽  
Polyketide Synthase Gene

Abstract Microbial biosynthetic gene clusters are a valuable source of bioactive molecules. However, because they typically represent a small fraction of genomic material in most metagenomic samples, it remains challenging to deeply sequence them. We present an approach to isolate and sequence gene clusters in metagenomic samples using microfluidic automated plasmid library enrichment. Our approach provides deep coverage of the target gene cluster, facilitating reassembly. We demonstrate the approach by isolating and sequencing type I polyketide synthase gene clusters from an Antarctic soil metagenome. Our method promotes the discovery of functional-related genes and biosynthetic pathways.

scholarly journals Heterologous expression of cryptomaldamide in a cyanobacterial host

2020 ◽  
Author(s):  
Arnaud Taton ◽  
Andrew Ecker ◽  
Brienna Diaz ◽  
Nathan A. Moss ◽  
Brooke Anderson ◽  
...  
Keyword(s):  
Heterologous Expression ◽  
High Titer ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Marine Cyanobacteria ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Genetic Tools ◽  
Genetic Manipulations

ABSTRACTFilamentous marine cyanobacteria make a variety of bioactive molecules that are produced by polyketide synthases, non-ribosomal peptide synthetases, and hybrid pathways that are encoded by large biosynthetic gene clusters. These cyanobacterial natural products represent potential drugs leads; however, thorough pharmacological investigations have been impeded by the limited quantity of compound that is typically available from the native organisms. Additionally, investigations of the biosynthetic gene clusters and enzymatic pathways have been difficult due to the inability to conduct genetic manipulations in the native producers. Here we report a set of genetic tools for the heterologous expression of biosynthetic gene clusters in the cyanobacteria Synechococcus elongatus PCC 7942 and Anabaena (Nostoc) PCC 7120. To facilitate the transfer of gene clusters in both strains, we engineered a strain of Anabaena that contains S. elongatus homologous sequences for chromosomal recombination at a neutral site and devised a CRISPR-based strategy to efficiently obtain segregated double recombinant clones of Anabaena. These genetic tools were used to express the large 28.7 kb cryptomaldamide biosynthetic gene cluster from the marine cyanobacterium Moorena (Moorea) producens JHB in both model strains. S. elongatus did not produce cryptomaldamide, however high-titer production of cryptomaldamide was obtained in Anabaena. The methods developed in this study will facilitate the heterologous expression of biosynthetic gene clusters isolated from marine cyanobacteria and complex metagenomic samples.Abstract Figure

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