scholarly journals Dual Role of GdmH in Producer Immunity and Secretion of the Staphylococcal Lantibiotics Gallidermin and Epidermin

2001 ◽  
Vol 67 (3) ◽  
pp. 1380-1383 ◽  
Author(s):  
Matthias Hille ◽  
Stefanie Kies ◽  
Friedrich Götz ◽  
Andreas Peschel
Keyword(s):  
Antimicrobial Peptides ◽  
Gene Clusters ◽  
Synergistic Activity ◽  
Biosynthetic Gene ◽  
Cellular Functions ◽  
Biosynthetic Gene Clusters ◽  
Atp Binding Cassette Transporters ◽  
Immunity Genes ◽  
Unique Genes

ABSTRACT The biosynthetic gene clusters of the staphylococcal lantibiotics epidermin and gallidermin are distinguished by the presence of the unique genes epiH and gdmH, respectively. They encode accessory factors for the ATP-binding cassette transporters that mediate secretion of the antimicrobial peptides. Here, we show thatgdmH also contributes to immunity to gallidermin but not to nisin. gdmH alone affected susceptibility to gallidermin only moderately, but it led to a multiplication of the immunity level mediated by the FEG immunity genes when cloned together with the gdmT gene, suggesting a synergistic activity of the H and FEG systems. gdmH-related genes were identified in the genomes of several bacteria, indicating an involvement in further cellular functions.

Screening of tenuazonic acid production-inducing compounds and identification of NPD938 as a regulator of fungal secondary metabolism

2021 ◽  
Author(s):  
Takayuki Motoyama ◽  
Tomoaki Ishii ◽  
Takashi Kamakura ◽  
Hiroyuki Osada
Keyword(s):  
Secondary Metabolism ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Tenuazonic Acid ◽  
Cellular Functions ◽  
Biosynthetic Gene Clusters ◽  
Chemical Library ◽  
Tea Production ◽  
Fungal Secondary Metabolism

Abstract The control of secondary metabolism in fungi is essential for the regulation of various cellular functions. In this study, we searched the RIKEN Natural Products Depository (NPDepo) chemical library for inducers of tenuazonic acid (TeA) production in the rice blast fungus Pyricularia oryzae and identified NPD938. NPD938 transcriptionally induced TeA production. We explored the mode of action of NPD938 and observed that this compound enhanced TeA production via LAE1, a global regulator of fungal secondary metabolism. NPD938 could also induce production of terpendoles and pyridoxatins in Tolypocladium album RK99-F33. Terpendole production was induced transcriptionally. We identified the pyridoxatin biosynthetic gene cluster among transcriptionally induced secondary metabolite biosynthetic gene clusters. Therefore, NPD938 is useful for the control of fungal secondary metabolism.

scholarly journals Identification and distribution of gene clusters required for synthesis of sphingolipid metabolism inhibitors in diverse species of the filamentous fungus Fusarium

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Hye-Seon Kim ◽  
Jessica M. Lohmar ◽  
Mark Busman ◽  
Daren W. Brown ◽  
Todd A. Naumann ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Sphingolipid Metabolism ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Dehydrogenase Gene ◽  
Food And Feed ◽  
Feed Safety

Abstract Background Sphingolipids are structural components and signaling molecules in eukaryotic membranes, and many organisms produce compounds that inhibit sphingolipid metabolism. Some of the inhibitors are structurally similar to the sphingolipid biosynthetic intermediate sphinganine and are referred to as sphinganine-analog metabolites (SAMs). The mycotoxins fumonisins, which are frequent contaminants in maize, are one family of SAMs. Due to food and feed safety concerns, fumonisin biosynthesis has been investigated extensively, including characterization of the fumonisin biosynthetic gene cluster in the agriculturally important fungi Aspergillus and Fusarium. Production of several other SAMs has also been reported in fungi, but there is almost no information on their biosynthesis. There is also little information on how widely SAM production occurs in fungi or on the extent of structural variation of fungal SAMs. Results Using fumonisin biosynthesis as a model, we predicted that SAM biosynthetic gene clusters in fungi should include a polyketide synthase (PKS), an aminotransferase and a dehydrogenase gene. Surveys of genome sequences identified five putative clusters with this three-gene combination in 92 of 186 Fusarium species examined. Collectively, the putative SAM clusters were distributed widely but discontinuously among the species. We propose that the SAM5 cluster confers production of a previously reported Fusarium SAM, 2-amino-14,16-dimethyloctadecan-3-ol (AOD), based on the occurrence of AOD production only in species with the cluster and on deletion analysis of the SAM5 cluster PKS gene. We also identified SAM clusters in 24 species of other fungal genera, and propose that one of the clusters confers production of sphingofungin, a previously reported Aspergillus SAM. Conclusion Our results provide a genomics approach to identify novel SAM biosynthetic gene clusters in fungi, which should in turn contribute to identification of novel SAMs with applications in medicine and other fields. Information about novel SAMs could also provide insights into the role of SAMs in the ecology of fungi. Such insights have potential to contribute to strategies to reduce fumonisin contamination in crops and to control crop diseases caused by SAM-producing fungi.

scholarly journals Synergistic activity of cosecreted natural products from amoebae-associated bacteria

2018 ◽  
Vol 115 (15) ◽  
pp. 3758-3763 ◽  
Author(s):  
Johannes Arp ◽  
Sebastian Götze ◽  
Ruchira Mukherji ◽  
Derek J. Mattern ◽  
María García-Altares ◽  
...  
Keyword(s):  
Natural Products ◽  
Polyketide Synthase ◽  
Bacterial Genome ◽  
Gene Clusters ◽  
Homoserine Lactone ◽  
Microbial Interactions ◽  
Signal Molecules ◽  
Synergistic Activity ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters

Investigating microbial interactions from an ecological perspective is a particularly fruitful approach to unveil both new chemistry and bioactivity. Microbial predator–prey interactions in particular rely on natural products as signal or defense molecules. In this context, we identified a grazing-resistant Pseudomonas strain, isolated from the bacterivorous amoeba Dictyostelium discoideum. Genome analysis of this bacterium revealed the presence of two biosynthetic gene clusters that were found adjacent to each other on a contiguous stretch of the bacterial genome. Although one cluster codes for the polyketide synthase producing the known antibiotic mupirocin, the other cluster encodes a nonribosomal peptide synthetase leading to the unreported cyclic lipopeptide jessenipeptin. We describe its complete structure elucidation, as well as its synergistic activity against methicillin-resistant Staphylococcus aureus, when in combination with mupirocin. Both biosynthetic gene clusters are regulated by quorum-sensing systems, with 3-oxo-decanoyl homoserine lactone (3-oxo-C10-AHL) and hexanoyl homoserine lactone (C6-AHL) being the respective signal molecules. This study highlights the regulation, richness, and complex interplay of bacterial natural products that emerge in the context of microbial competition.

scholarly journals Deciphering the Microbial Taxonomy and Functionality of Two Diverse Mangrove Ecosystems and Their Potential Abilities To Produce Bioactive Compounds

mSystems ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Shuilin Liao ◽  
Yayu Wang ◽  
Huan Liu ◽  
Guangyi Fan ◽  
Sunil Kumar Sahu ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
De Novo ◽  
Southern China ◽  
Sulfur Metabolism ◽  
Gene Clusters ◽  
Metagenomic Sequencing ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Mangrove Ecosystems ◽  
Unique Genes

ABSTRACT Mangroves, as important and special ecosystems, create unique ecological environments for examining the microbial gene capacity and potential for producing bioactive compounds. However, little is known about the biogeochemical implications of microbiomes in mangrove ecosystems, especially the variations between pristine and anthropogenic mangroves. To elucidate this, we investigated the microbial taxonomic and functional shifts of the mangrove microbiomes and their potential for bioactive compounds in two different coastal mangrove ecosystems in southern China. A gene catalogue, including 87 million unique genes, was constructed, based on deep shotgun metagenomic sequencing. Differentially enriched bacterial and archaeal taxa between pristine mangroves (Guangxi) and anthropogenic mangroves (Shenzhen) were found. The Nitrospira and ammonia-oxidizing archaea, specifically, were more abundant in Shenzhen mangroves, while sulfate-reducing bacteria and methanogens were more abundant in Guangxi mangroves. The results of functional analysis were consistent with the taxonomic results, indicating that the Shenzhen mangrove microbiome has a higher abundance of genes involved in nitrogen metabolism while the Guangxi mangrove microbiome has a higher capacity for sulfur metabolism and methanogenesis. Biosynthetic gene clusters were identified in the metagenome data and in hundreds of de novo reconstructed nonredundant microbial genomes, respectively. Notably, we found different biosynthetic potential in different taxa, and we identified three high quality and novel Acidobacteria genomes with a large number of BGCs. In total, 67,278 unique genes were annotated with antibiotic resistance, indicating the prevalence and persistence in multidrug-resistant genes in the mangrove microbiome. IMPORTANCE This study comprehensively described the taxonomy and functionality of mangrove microbiomes, including their capacity for secondary metabolite biosynthesis and their ability to resist antibiotics. The microbial taxonomic and functional characteristics differed between geographical locations, corresponding to the environmental condition of two diverse mangrove regions. A large number of microbial biosynthetic gene clusters encoding novel bioactivities were found, and this can serve as a valuable resource to guide novel bioactive compound discovery for potential clinical uses.

Fungal Dihydroxynaphthalene-Melanin: Diversity-Oriented Biosynthesis through Enzymatic and Non-enzymatic Transformations

Synlett ◽  
2017 ◽  
Vol 28 (18) ◽  
pp. 2360-2372 ◽  
Author(s):  
Michael Müller ◽  
Syed Husain
Keyword(s):  
Biosynthetic Pathway ◽  
Molecular Diversity ◽  
Magnaporthe Grisea ◽  
Gene Clusters ◽  
Extended Model ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Melanin Biosynthesis ◽  
Aromatic Polyketides

Tetrahydroxynaphthalene reductase (T4HNR) from Magnaporthe grisea catalyzes the reduction of polyhydroxynaphthalenes, hydroxynaphthoquinones, and 1,4-diketones, with extensive ramifications for the biosynthesis of (shunt) metabolites related to 1,8-dihydroxynaphthalene (DHN)-melanin biosynthesis. Hence, an extended model for DHN-melanin biosynthesis has been developed which is based on a screening hypothesis involving non-enzymatic transformations such as oxidations and tautomerism. This has led to the broadening of the functions of several short-chain dehydrogenases/reductases (SDRs) capable of reducing polyhydroxyanthracenes, polyhydroxynaphthalenes, and polyhydroxybenzenes. Our work, broadening the scope of enzymatic dearomatization reactions, provides access to the biocatalytic synthesis of a variety of natural and natural-like products. Furthermore, the results described in this account provide the basis for the identification of other SDRs amenable to reducing aromatic compounds, and thus enable the identification of biosynthetic gene clusters most likely involved in the biosynthesis of aromatic polyketides.1 Introduction2 Biosynthesis of 1,8-Dihydroxynaphthalene (DHN)3 Biosynthesis of Shunt Metabolites and the Origin of Molecular Diversity3.1 Role of Spontaneous Non-enzymatic Oxidations3.2 Role of T4HNR and T3HNR3.3 Role of Tautomerism in the Biosynthesis of (Shunt) Metabolites4 Extended Melanin Biosynthesis: A Screening Hypothesis5 Useful Outcomes of the Newly Identified Melanin Biosynthetic Pathway5.1 NADP+ Regeneration Using Lawsone as Mediator5.2 Anthrahydroquinone as an Intermediate in the Biosynthesis of Chrysophanol and Other Anthraquinone-Derived Products5.3 Combination of T3HNR and GDH To Access trans-Ketodiols5.4 Phloroglucinol Reductases (PGRs) To Dearomatize Monomeric Phenols6 Conclusion

scholarly journals Influence of Amino Acid Feeding on Production of Calcimycin and Analogs in Streptomyces chartreusis

2021 ◽  
Vol 18 (16) ◽  
pp. 8740
Author(s):  
Kirstin I. Arend ◽  
Julia E. Bandow
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Nitrogen Sources ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Defined Medium ◽  
Glutamine Supplementation ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters

Streptomyces chartreusis NRRL 3882 produces the polyether ionophore calcimycin and a variety of analogs, which originate from the same biosynthetic gene cluster. The role of calcimycin and its analogs for the producer is unknown, but calcimycin has strong antibacterial activity. Feeding experiments were performed in chemically defined medium systematically supplemented with proteinogenic amino acids to analyze their individual effects on calcimycin synthesis. In the culture supernatants, in addition to known calcimycin analogs, eight so far unknown analogs were detected using LC-MS/MS. Under most conditions cezomycin was the compound produced in highest amounts. The highest production of calcimycin was detected upon feeding with glutamine. Supplementation of the medium with glutamic acid resulted in a decrease in calcimycin production, and supplementation of other amino acids such as tryptophan, lysine, and valine resulted in the decrease in the synthesis of calcimycin and of the known intermediates of the biosynthetic pathway. We demonstrated that the production of calcimycin and its analogs is strongly dependent on amino acid supply. Utilization of amino acids as precursors and as nitrogen sources seem to critically influence calcimycin synthesis. Even amino acids not serving as direct precursors resulted in a different product profile regarding the stoichiometry of calcimycin analogs. Only slight changes in cultivation conditions can lead to major changes in the metabolic output, which highlights the hidden potential of biosynthetic gene clusters. We emphasize the need to further study the extent of this potential to understand the ecological role of metabolite diversity originating from single biosynthetic gene clusters.

scholarly journals Phages weaponize their bacteria with biosynthetic gene clusters

2020 ◽  
Author(s):  
Anna Dragoš ◽  
Aaron J.C. Andersen ◽  
Carlos N. Lozano-Andrade ◽  
Paul J. Kempen ◽  
Ákos T. Kovács ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Specialized Metabolites ◽  
Fitness Advantage ◽  
Large Step ◽  
Bioactive Potential ◽  
Close Relatives

ABSTRACTBacteria produce many different specialized metabolites, which are encoded by biosynthetic gene clusters (BGCs). Despite high industrial relevance owing to broad bioactive potential of these metabolites, their ecological roles remain largely unexplored. We analyze all available genomes for BGCs of phage origin. The BGCs predominantly reside within temperate phages infecting certain commensal and pathogenic bacteria. Nearly all phage BGCs encode bacteriocins, which appear to serve as a strong proxy for phage specificity. Using the gut-associated bacterium Bacillus subtilis, we demonstrate how a temperate phage equips its host with a functional BGC, providing it with a competitive fitness advantage over close relatives. Therefore, certain temperate phages use BGCs to weaponize their bacteria against close relatives, leading to evolutionary benefits from lysogeny to the infected host, and hence, to the phage itself. Our study is a large step towards understanding the natural role of specialized metabolites, as well as mutualistic phage-host relationships.

Expanding the Natural Products Heterologous Expression Repertoire in the Model Cyanobacterium Anabaena sp. Strain PCC 7120: Production of Pendolmycin and Teleocidin B-4

2019 ◽  
Author(s):  
Patrick Videau ◽  
Kaitlyn Wells ◽  
Arun Singh ◽  
Jessie Eiting ◽  
Philip Proteau ◽  
...  
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Gene Clusters ◽  
Combinatorial Biosynthesis ◽  
Test Case ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Cyanobacterium Anabaena ◽  
Anabaena Sp ◽  
Pcc 7120

Cyanobacteria are prolific producers of natural products and genome mining has shown that many orphan biosynthetic gene clusters can be found in sequenced cyanobacterial genomes. New tools and methodologies are required to investigate these biosynthetic gene clusters and here we present the use of <i>Anabaena </i>sp. strain PCC 7120 as a host for combinatorial biosynthesis of natural products using the indolactam natural products (lyngbyatoxin A, pendolmycin, and teleocidin B-4) as a test case. We were able to successfully produce all three compounds using codon optimized genes from Actinobacteria. We also introduce a new plasmid backbone based on the native <i>Anabaena</i>7120 plasmid pCC7120ζ and show that production of teleocidin B-4 can be accomplished using a two-plasmid system, which can be introduced by co-conjugation.

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