scholarly journals Influence of Niche-Specific Nutrients on Secondary Metabolism in Vibrionaceae

2016 ◽  
Vol 82 (13) ◽  
pp. 4035-4044 ◽  
Author(s):  
Sonia Giubergia ◽  
Christopher Phippen ◽  
Charlotte H. Gotfredsen ◽  
Kristian Fog Nielsen ◽  
Lone Gram
Keyword(s):  
Antibacterial Activity ◽  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Natural Environment ◽  
High Resolution Mass Spectrometry ◽  
Fold Increase ◽  
Gene Clusters ◽  
Growth Potential ◽  
Antibacterial Compounds ◽  
Content Type

ABSTRACTMany factors, such as the substrate and the growth phase, influence biosynthesis of secondary metabolites in microorganisms. Therefore, it is crucial to consider these factors when establishing a bioprospecting strategy. Mimicking the conditions of the natural environment has been suggested as a means of inducing or influencing microbial secondary metabolite production. The purpose of the present study was to determine how the bioactivity ofVibrionaceaewas influenced by carbon sources typical of their natural environment. We determined how mannose and chitin, compared to glucose, influenced the antibacterial activity of a collection ofVibrionaceaestrains isolated because of their ability to produce antibacterial compounds but that in subsequent screenings seemed to have lost this ability. The numbers of bioactive isolates were 2- and 3.5-fold higher when strains were grown on mannose and chitin, respectively, than on glucose. As secondary metabolites are typically produced during late growth, potential producers were also allowed 1 to 2 days of growth before exposure to the pathogen. This strategy led to a 3-fold increase in the number of bioactive strains on glucose and an 8-fold increase on both chitin and mannose. We selected two bioactive strains belonging to species for which antibacterial activity had not previously been identified. Using ultrahigh-performance liquid chromatography–high-resolution mass spectrometry and bioassay-guided fractionation, we found that the siderophore fluvibactin was responsible for the antibacterial activity ofVibrio furnissiiandVibrio fluvialis. These results suggest a role of chitin in the regulation of secondary metabolism in vibrios and demonstrate that considering bacterial ecophysiology during development of screening strategies will facilitate bioprospecting.IMPORTANCEA challenge in microbial natural product discovery is the elicitation of the biosynthetic gene clusters that are silent when microorganisms are grown under standard laboratory conditions. We hypothesized that, since the clusters are not lost during proliferation in the natural niche of the microorganisms, they must, under such conditions, be functional. Here, we demonstrate that an ecology-based approach in which the producer organism is allowed a temporal advantage and where growth conditions are mimicking the natural niche remarkably increases the number ofVibrionaceaestrains producing antibacterial compounds.

scholarly journals Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
M. T. Drott ◽  
R. W. Bastos ◽  
A. Rokas ◽  
L. N. A. Ries ◽  
T. Gabaldón ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Aspergillus Nidulans ◽  
Reference Genome ◽  
Genetic Model ◽  
High Resolution Mass Spectrometry ◽  
Gene Clusters ◽  
Clinical Isolates ◽  
Biosynthetic Gene ◽  
Content Type ◽  
Natural Diversity

ABSTRACT The filamentous fungus Aspergillus nidulans has been a primary workhorse used to understand fungal genetics. Much of this work has focused on elucidating the genetics of biosynthetic gene clusters (BGCs) and the secondary metabolites (SMs) they produce. SMs are both niche defining in fungi and of great economic importance to humans. Despite the focus on A. nidulans, very little is known about the natural diversity in secondary metabolism within this species. We determined the BGC content and looked for evolutionary patterns in BGCs from whole-genome sequences of two clinical isolates and the A4 reference genome of A. nidulans. Differences in BGC content were used to explain SM profiles determined using liquid chromatography–high-resolution mass spectrometry. We found that in addition to genetic variation of BGCs contained by all isolates, nine BGCs varied by presence/absence. We discovered the viridicatumtoxin BGC in A. nidulans and suggest that this BGC has undergone a horizontal gene transfer from the Aspergillus section Nigri lineage into Penicillium sometime after the sections Nigri and Nidulantes diverged. We identified the production of viridicatumtoxin and several other compounds previously not known to be produced by A. nidulans. One isolate showed a lack of sterigmatocystin production even though it contained an apparently intact sterigmatocystin BGC, raising questions about other genes and processes known to regulate this BGC. Altogether, our work uncovers a large degree of intraspecies diversity in BGC and SM production in this genetic model species and offers new avenues to understand the evolution and regulation of secondary metabolism. IMPORTANCE Much of what we know about the genetics underlying secondary metabolite (SM) production and the function of SMs in the model fungus Aspergillus nidulans comes from a single reference genome. A growing body of research indicates the importance of biosynthetic gene cluster (BGC) and SM diversity within a species. However, there is no information about the natural diversity of secondary metabolism in A. nidulans. We discovered six novel clusters that contribute to the considerable variation in both BGC content and SM production within A. nidulans. We characterize a diverse set of mutations and emphasize how findings of single nucleotide polymorphisms (SNPs), deletions, and differences in evolutionary history encompass much of the variation observed in nonmodel systems. Our results emphasize that A. nidulans may also be a strong model to use within-species diversity to elucidate regulatory cross talk, fungal ecology, and drug discovery systems.

scholarly journals Characterizing the Pathogenic, Genomic, and Chemical Traits ofAspergillus fischeri, a Close Relative of the Major Human Fungal PathogenAspergillus fumigatus

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Matthew E. Mead ◽  
Sonja L. Knowles ◽  
Huzefa A. Raja ◽  
Sarah R. Beattie ◽  
Caitlin H. Kowalski ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Aspergillus Fumigatus ◽  
Secondary Metabolism ◽  
Human Disease ◽  
Chemical Characterization ◽  
Gene Clusters ◽  
Invasive Disease ◽  
Close Relative ◽  
Low Oxygen ◽  
Content Type

ABSTRACTAspergillus fischeriis closely related toAspergillus fumigatus, the major cause of invasive mold infections. Even thoughA. fischeriis commonly found in diverse environments, including hospitals, it rarely causes invasive disease. WhyA. fischericauses less human disease thanA. fumigatusis unclear. A comparison ofA. fischeriandA. fumigatusfor pathogenic, genomic, and secondary metabolic traits revealed multiple differences in pathogenesis-related phenotypes. We observed thatA. fischeriNRRL 181 is less virulent thanA. fumigatusstrain CEA10 in multiple animal models of disease, grows slower in low-oxygen environments, and is more sensitive to oxidative stress. Strikingly, the observed differences for some traits are of the same order of magnitude as those previously reported betweenA. fumigatusstrains. In contrast, similar to what has previously been reported, the two species exhibit high genomic similarity; ∼90% of theA. fumigatusproteome is conserved inA. fischeri, including 48/49 genes known to be involved inA. fumigatusvirulence. However, only 10/33A. fumigatusbiosynthetic gene clusters (BGCs) likely involved in secondary metabolite production are conserved inA. fischeriand only 13/48A. fischeriBGCs are conserved inA. fumigatus. Detailed chemical characterization ofA. fischericultures grown on multiple substrates identified multiple secondary metabolites, including two new compounds and one never before isolated as a natural product. Additionally, anA. fischerideletion mutant oflaeA, a master regulator of secondary metabolism, produced fewer secondary metabolites and in lower quantities, suggesting that regulation of secondary metabolism is at least partially conserved. These results suggest that the nonpathogenicA. fischeripossesses many of the genes important forA. fumigatuspathogenicity but is divergent with respect to its ability to thrive under host-relevant conditions and its secondary metabolism.IMPORTANCEAspergillus fumigatusis the primary cause of aspergillosis, a devastating ensemble of diseases associated with severe morbidity and mortality worldwide.A. fischeriis a close relative ofA. fumigatusbut is not generally observed to cause human disease. To gain insights into the underlying causes of this remarkable difference in pathogenicity, we compared two representative strains (one from each species) for a range of pathogenesis-relevant biological and chemical characteristics. We found that disease progression in multipleA. fischerimouse models was slower and caused less mortality thanA. fumigatus. Remarkably, the observed differences betweenA. fischeriandA. fumigatusstrains examined here closely resembled those previously described for two commonly studiedA. fumigatusstrains, AF293 and CEA10.A. fischeriandA. fumigatusexhibited different growth profiles when placed in a range of stress-inducing conditions encountered during infection, such as low levels of oxygen and the presence of chemicals that induce the production of reactive oxygen species. We also found that the vast majority ofA. fumigatusgenes known to be involved in virulence are conserved inA. fischeri, whereas the two species differ significantly in their secondary metabolic pathways. These similarities and differences that we report here are the first step toward understanding the evolutionary origin of a major fungal pathogen.

scholarly journals Complete Genome Sequences of Three Bacillus amyloliquefaciens Strains That Inhibit the Growth of Listeria monocytogenes In Vitro

2018 ◽  
Vol 6 (25) ◽  
Author(s):  
Thao D. Tran ◽  
Steven Huynh ◽  
Craig T. Parker ◽  
Robert Hnasko ◽  
Lisa Gorski ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Secondary Metabolites ◽  
Growth Inhibition ◽  
Complete Genome ◽  
Bacillus Amyloliquefaciens ◽  
Gene Clusters ◽  
Genome Sequences ◽  
Multiple Gene ◽  
Content Type

ABSTRACT Here, we report the complete genome sequences of three Bacillus amyloliquefaciens strains isolated from alfalfa, almond drupes, and grapes that inhibited the growth of Listeria monocytogenes strain 2011L-2857 in vitro. We also report multiple gene clusters encoding secondary metabolites that may be responsible for the growth inhibition of L. monocytogenes.

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 Genomic and Metabolomic Analysis of Antarctic Bacteria Revealed Culture and Elicitation Conditions for the Production of Antimicrobial Compounds

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 673
Author(s):  
Kattia Núñez-Montero ◽  
Damián Quezada-Solís ◽  
Zeinab G. Khalil ◽  
Robert J. Capon ◽  
Fernando D. Andreote ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Secondary Metabolites ◽  
Culture Media ◽  
Genome Mining ◽  
Gene Clusters ◽  
Culture Conditions ◽  
Bioactive Metabolites ◽  
Bacterial Strains ◽  
Antarctic Bacteria ◽  
New Antibiotics

Concern about finding new antibiotics against drug-resistant pathogens is increasing every year. Antarctic bacteria have been proposed as an unexplored source of bioactive metabolites; however, most biosynthetic gene clusters (BGCs) producing secondary metabolites remain silent under common culture conditions. Our work aimed to characterize elicitation conditions for the production of antibacterial secondary metabolites from 34 Antarctic bacterial strains based on MS/MS metabolomics and genome mining approaches. Bacterial strains were cultivated under different nutrient and elicitation conditions, including the addition of lipopolysaccharide (LPS), sodium nitroprusside (SNP), and coculture. Metabolomes were obtained by HPLC-QTOF-MS/MS and analyzed through molecular networking. Antibacterial activity was determined, and seven strains were selected for genome sequencing and analysis. Biosynthesis pathways were activated by all the elicitation treatments, which varies among strains and dependents of culture media. Increased antibacterial activity was observed for a few strains and addition of LPS was related with inhibition of Gram-negative pathogens. Antibiotic BGCs were found for all selected strains and the expressions of putative actinomycin, carotenoids, and bacillibactin were characterized by comparison of genomic and metabolomic data. This work established the use of promising new elicitors for bioprospection of Antarctic bacteria and highlights the importance of new “-omics” comparative approaches for drug discovery.

scholarly journals Unusual and Highly Bioactive Sesterterpenes Synthesized by Pleurotus ostreatus during Coculture with Trametes robiniophila Murr

2019 ◽  
Vol 85 (14) ◽  
Author(s):  
Xiao-Ting Shen ◽  
Xu-Hua Mo ◽  
Li-Ping Zhu ◽  
Ling-Ling Tan ◽  
Feng-Yu Du ◽  
...  
Keyword(s):  
Network Analysis ◽  
Secondary Metabolites ◽  
Pleurotus Ostreatus ◽  
Pathogenic Fungi ◽  
Gene Clusters ◽  
Molecular Network ◽  
Terpene Synthase ◽  
High Morbidity ◽  
Content Type ◽  
Trametes Robiniophila

ABSTRACT Candida albicans and Cryptococcus neoformans, human-pathogenic fungi found worldwide, are receiving increasing attention due to high morbidity and mortality in immunocompromised patients. In the present work, 110 fungus pairs were constructed by coculturing 16 wood-decaying basidiomycetes, among which coculture of Trametes robiniophila Murr and Pleurotus ostreatus was found to strongly inhibit pathogenic fungi through bioactivity-guided assays. A combination of metabolomics and molecular network analysis revealed that 44 features were either newly synthesized or produced at high levels in this coculture system and that 6 of the features that belonged to a family of novel and unusual linear sesterterpenes contributed to high activity with MICs of 1 to 32 μg/ml against pathogenic fungi. Furthermore, dynamic 13C-labeling analysis revealed an association between induced features and the corresponding fungi. Unusual sesterterpenes were 13C labeled only in P. ostreatus in a time course after stimulation by the coculture, suggesting that these sesterterpenes were synthesized by P. ostreatus instead of T. robiniophila Murr. Sesterterpene compounds 1 to 3 were renamed postrediene A to C. Real-time reverse transcription-quantitative PCR (RT-qPCR) analysis revealed that transcriptional levels of three genes encoding terpene synthase, farnesyl-diphosphate farnesyltransferase, and oxidase were found to be 8.2-fold, 88.7-fold, and 21.6-fold higher, respectively, in the coculture than in the monoculture, indicating that biosynthetic gene cluster 10 was most likely responsible for the synthesis of these sesterterpenes. A putative biosynthetic pathway of postrediene A to postrediene C was then proposed based on structures of sesterterpenes and molecular network analysis. IMPORTANCE A number of gene clusters involved in biosynthesis of secondary metabolites are presumably silent or expressed at low levels under conditions of standard laboratory cultivation, resulting in a large gap between the pool of discovered metabolites and genome capability. This work mimicked naturally occurring competition by construction of an artificial coculture of basidiomycete fungi for the identification of secondary metabolites with novel scaffolds and excellent bioactivity. Unusual linear sesterterpenes of postrediene A to C synthesized by P. ostreatus not only were promising lead drugs against human-pathogenic fungi but also highlighted a distinct pathway for sesterterpene biosynthesis in basidiomycetes. The current work provides an important basis for uncovering novel gene functions involved in sesterterpene synthesis and for gaining insights into the mechanism of silent gene activation in fungal defense.

scholarly journals A Novel AdpA Homologue Negatively Regulates Morphological Differentiation inStreptomyces xiamenensis318

2019 ◽  
Vol 85 (7) ◽  
Author(s):  
Xu-Liang Bu ◽  
Jing-Yi Weng ◽  
Bei-Bei He ◽  
Min-Juan Xu ◽  
Jun Xu
Keyword(s):  
Cell Growth ◽  
Secondary Metabolism ◽  
Gene Cluster ◽  
Morphological Differentiation ◽  
Gene Clusters ◽  
Transcriptional Level ◽  
Negative Effects ◽  
Promoter Regions ◽  
Content Type ◽  
Enhanced Production

ABSTRACTThe pleiotropic transcriptional regulator AdpA positively controls morphological differentiation and regulates secondary metabolism in mostStreptomycesspecies.Streptomyces xiamenensis318 has a linear chromosome 5.96 Mb in size. How AdpA affects secondary metabolism and morphological differentiation in such a naturally minimized genomic background is unknown. Here, we demonstrated that AdpASx, an AdpA orthologue inS. xiamenensis, negatively regulates cell growth and sporulation and bidirectionally regulates the biosynthesis of xiamenmycin and polycyclic tetramate macrolactams (PTMs) inS. xiamenensis318. Overexpression of theadpASxgene inS. xiamenensis318 had negative effects on morphological differentiation and resulted in reduced transcription of putativessgA,ftsZ,ftsH,amfC,whiB,wblA1,wblA2,wblE, and a gene encoding sporulation-associated protein (sxim_29740), whereas the transcription of putativebldDandbldAgenes was upregulated. Overexpression ofadpASxled to significantly enhanced production of xiamenmycin but had detrimental effects on the production of PTMs. As expected, the transcriptional level of theximgene cluster was upregulated, whereas the PTM gene cluster was downregulated. Moreover, AdpASxnegatively regulated the transcription of its own gene. Electrophoretic mobility shift assays revealed that AdpASxcan bind the promoter regions of structural genes of both theximand PTM gene clusters as well as to the promoter regions of genes potentially involved in the cell growth and differentiation ofS. xiamenensis318. We report that an AdpA homologue has negative effects on morphological differentiation inS. xiamenensis318, a finding confirmed when AdpASxwas introduced into the heterologous hostStreptomyces lividansTK24.IMPORTANCEAdpA is a key regulator of secondary metabolism and morphological differentiation inStreptomycesspecies. However, AdpA had not been reported to negatively regulate morphological differentiation. Here, we characterized the regulatory role of AdpASxinStreptomyces xiamenensis318, which has a naturally streamlined genome. In this strain, AdpASxnegatively regulated cell growth and morphological differentiation by directly controlling genes associated with these functions. AdpASxalso bidirectionally controlled the biosynthesis of xiamenmycin and PTMs by directly regulating their gene clusters rather than through other regulators. Our findings provide additional evidence for the versatility of AdpA in regulating morphological differentiation and secondary metabolism inStreptomyces.

scholarly journals Functional Operons in Secondary Metabolic Gene Clusters in Glarea lozoyensis (Fungi, Ascomycota, Leotiomycetes)

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Qun Yue ◽  
Li Chen ◽  
Yan Li ◽  
Gerald F. Bills ◽  
Xinyu Zhang ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Transcriptional Level ◽  
Tetramic Acid ◽  
Protein Coding ◽  
Content Type ◽  
Eukaryotic Gene ◽  
Transcriptional Units ◽  
Gene Structures

ABSTRACT Operons are multigene transcriptional units which occur mostly in prokaryotes but rarely in eukaryotes. Protein-coding operons have not been reported in the Fungi even though they represent a very diverse kingdom of organisms. Here, we report a functional operon involved in the secondary metabolism of the fungus Glarea lozoyensis belonging to Leotiomycetes (Ascomycota). Two contiguous genes, glpks3 and glnrps7, encoding polyketide synthase and nonribosomal peptide synthetase, respectively, are cotranscribed into one dicistronic mRNA under the control of the same promoter, and the mRNA is then translated into two individual proteins, GLPKS3 and GLNRPS7. Heterologous expression in Aspergillus nidulans shows that the GLPKS3-GLNRPS7 enzyme complex catalyzes the biosynthesis of a novel pyrrolidinedione-containing compound, xenolozoyenone (compound 1), which indicates the operon is functional. Although it is structurally similar to prokaryotic operons, the glpks3-glnrps7 operon locus has a monophylogenic origin from fungi rather than having been horizontally transferred from prokaryotes. Moreover, two additional operons, glpks28-glnrps8 and glpks29-glnrps9, were verified at the transcriptional level in the same fungus. This is the first report of protein-coding operons in a member of the Fungi. IMPORTANCE Operons are multigene transcriptional units which occur mostly in prokaryotes but rarely in eukaryotes. Three operon-like gene structures for secondary metabolism that were discovered in the filamentous fungus Glarea lozoyensis are the first examples of protein-coding operons identified in a member of the Fungi. Among them, the glpks3-glnrps7 operon is responsible for the biosynthesis of xenolozoyenone, which is a novel tetramic acid-containing compound. Although structurally similar to prokaryotic operons, the glpks3-glnrps7 operon locus did not result from horizontal gene transfer from prokaryotes. In addition, operonlike structures have been predicted in silico to be common in other fungi. The common occurrence and operonlike structure in fungi provide evolutionary insight and essential data for eukaryotic gene transcription.

scholarly journals Influence of Iron on Production of the Antibacterial Compound Tropodithietic Acid and Its Noninhibitory Analog in Phaeobacter inhibens

2015 ◽  
Vol 82 (2) ◽  
pp. 502-509 ◽  
Author(s):  
Paul W. D'Alvise ◽  
Christopher B. W. Phippen ◽  
Kristian F. Nielsen ◽  
Lone Gram
Keyword(s):  
Mass Spectrometry ◽  
Antibacterial Activity ◽  
High Resolution Mass Spectrometry ◽  
Biologically Active ◽  
Brown Pigment ◽  
Marine Broth ◽  
Content Type ◽  
Tropodithietic Acid ◽  
Antibacterial Compound ◽  
Phaeobacter Inhibens

ABSTRACTTropodithietic acid (TDA) is an antibacterial compound produced by somePhaeobacterandRuegeriaspp. of theRoseobacterclade. TDA production is studied in marine broth or agar since antibacterial activity in other media is not observed. The purpose of this study was to determine how TDA production is influenced by substrate components. High concentrations of ferric citrate, as present in marine broth, or other iron sources were required for production of antibacterially active TDA. However, when supernatants of noninhibitory, low-iron cultures ofPhaeobacter inhibenswere acidified, antibacterial activity was detected in a bioassay. The absence of TDA in nonacidified cultures and the presence of TDA in acidified cultures were verified by liquid chromatography–high-resolution mass spectrometry. A noninhibitory TDA analog (pre-TDA) was produced byP. inhibens,Ruegeria mobilisF1926, andPhaeobactersp. strain 27-4 under low-iron concentrations and was instantaneously converted to TDA when pH was lowered. Production of TDA in the presence of Fe3+coincides with formation of a dark brown substance, which could be precipitated by acid addition. From this brown pigment TDA could be liberated slowly with aqueous ammonia, and both direct-infusion mass spectrometry and elemental analysis indicated a [FeIII(TDA)2]xcomplex. The pigment could also be produced by precipitation of pure TDA with FeCl3. Our results raise questions about how biologically active TDA is produced in natural marine settings where iron is typically limited and whether the affinity of TDA to iron points to a physiological or ecological function of TDA other than as an antibacterial compound.

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