scholarly journals An IgaA/UmoB Family Protein fromSerratia marcescensRegulates Motility, Capsular Polysaccharide Biosynthesis, and Secondary Metabolite Production

2018 ◽  
Vol 84 (6) ◽  
Author(s):  
Nicholas A. Stella ◽  
Kimberly M. Brothers ◽  
Jake D. Callaghan ◽  
Angelina M. Passerini ◽  
Cihad Sigindere ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Intracellular Signaling ◽  
Biofilm Formation ◽  
Capsular Polysaccharide ◽  
Biologically Active ◽  
Public Health Importance ◽  
Content Type ◽  
Polysaccharide Biosynthesis ◽  
Transcriptional Changes

ABSTRACTSecondary metabolites are an important source of pharmaceuticals and key modulators of microbe-microbe interactions. The bacteriumSerratia marcescensis part of theEnterobacteriaceaefamily of eubacteria and produces a number of biologically active secondary metabolites. In this study, we screened for novel regulators of secondary metabolites synthesized by a clinical isolate ofS. marcescensand found mutations in a gene for an uncharacterized UmoB/IgaA family member here namedgumB. Mutation ofgumBconferred a severe loss of the secondary metabolites prodigiosin and serratamolide. ThegumBmutation conferred pleiotropic phenotypes, including altered biofilm formation, highly increased capsular polysaccharide production, and loss of swimming and swarming motility. These phenotypes corresponded to transcriptional changes infimA,wecA, andflhD. Unlike other UmoB/IgaA family members,gumBwas found to be not essential for growth inS. marcescens, yetigaAfromSalmonella enterica,yrfFfromEscherichia coli, and an uncharacterized predicted ortholog fromKlebsiella pneumoniaecomplemented thegumBmutant secondary metabolite defects, suggesting highly conserved function. These data support the idea that UmoB/IgaA family proteins are functionally conserved and extend the known regulatory influence of UmoB/IgaA family proteins to the control of competition-associated secondary metabolites and biofilm formation.IMPORTANCEIgaA/UmoB family proteins are found in members of theEnterobacteriaceaefamily of bacteria, which are of environmental and public health importance. IgaA/UmoB family proteins are thought to be inner membrane proteins that report extracellular stresses to intracellular signaling pathways that respond to environmental challenge. This study introduces a new member of the IgaA/UmoB family and demonstrates a high degree of functional similarity between IgaA/UmoB family proteins. Moreover, this study extends the phenomena controlled by IgaA/UmoB family proteins to include the biosynthesis of antimicrobial secondary metabolites.

scholarly journals Response of Secondary Metabolism of Hypogean Actinobacterial Genera to Chemical and Biological Stimuli

2018 ◽  
Vol 84 (19) ◽  
Author(s):  
Brett C. Covington ◽  
Jeffrey M. Spraggins ◽  
Audrey E. Ynigez-Gutierrez ◽  
Zachary B. Hylton ◽  
Brian O. Bachmann
Keyword(s):  
Secondary Metabolites ◽  
Small Molecules ◽  
Mixed Culture ◽  
Secondary Metabolite ◽  
Biologically Active ◽  
Secondary Metabolite Production ◽  
Microbial Culture ◽  
Content Type ◽  
Metabolite Production ◽  
Comparative Metabolomics

ABSTRACT Microorganisms within microbial communities respond to environmental challenges by producing biologically active secondary metabolites, yet the majority of these small molecules remain unidentified. We have previously demonstrated that secondary metabolite biosynthesis in actinomycetes can be activated by model environmental chemical and biological stimuli, and metabolites can be identified by comparative metabolomics analyses under different stimulus conditions. Here, we surveyed the secondary metabolite productivity of a group of 20 phylogenetically diverse actinobacteria isolated from hypogean (cave) environments by applying a battery of stimuli consisting of exposure to antibiotics, metals, and mixed microbial culture. Comparative metabolomics was used to reveal secondary metabolite responses from stimuli. These analyses revealed substantial changes in global metabolomic dynamics, with over 30% of metabolomic features increasing more than 10-fold under at least one stimulus condition. Selected features were isolated and identified via nuclear magnetic resonance (NMR), revealing several known secondary metabolite families, including the tetarimycins, aloesaponarins, hypogeamicins, actinomycins, and propeptins. One prioritized metabolite was identified to be a previously unreported aminopolyol polyketide, funisamine, produced by a cave isolate of Streptosporangium when exposed to mixed culture. The production of funisamine was most significantly increased in mixed culture with Bacillus species. The biosynthetic gene cluster responsible for the production of funisamine was identified via genomic sequencing of the producing strain, Streptosporangium sp. strain KDCAGE35, which facilitated a deduction of its biosynthesis. Together, these data demonstrate that comparative metabolomics can reveal the stimulus-induced production of natural products from diverse microbial phylogenies. IMPORTANCE Microbial secondary metabolites are an important source of biologically active and therapeutically relevant small molecules. However, much of this active molecular diversity is challenging to access due to low production levels or difficulty in discerning secondary metabolites within complex microbial extracts prior to isolation. Here, we demonstrate that ecological stimuli increase secondary metabolite production in phylogenetically diverse actinobacteria isolated from understudied hypogean environments. Additionally, we show that comparative metabolomics linking stimuli to metabolite response data can effectively reveal secondary metabolites within complex biological extracts. This approach highlighted secondary metabolites in almost all observed natural product classes, including low-abundance analogs of biologically relevant metabolites, as well as a new linear aminopolyol polyketide, funisamine. This study demonstrates the generality of activating stimuli to potentiate secondary metabolite production across diverse actinobacterial genera.

scholarly journals Urgensi dan Mekanisme Biosintesis Metabolit Sekunder Mikroba Laut

2012 ◽  
Vol 10 (2) ◽  
pp. 120 ◽  
Author(s):  
Risa Nofiani
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Metabolic Pathways ◽  
Abiotic Factors ◽  
Biologically Active ◽  
Secondary Metabolite Production ◽  
Marine Microorganism ◽  
Metabolite Production ◽  
Biotic And Abiotic Factors ◽  
Living Materials

Marine microorganism is one of biologically active potential resources of secondary metabolites. Its potency areso promising that the knowledge of how its secondary metabolite occured need to be studied and collected. Thoseknowledges will enable further study is improving secondary metabolite production in the laboratory. In nature,secondary metabolites synthesis occur when there are effect of both biotic and abiotic factors such as sea waterand microbe symbiosis with other living materials. When this is explained in metabolic pathways, secondarymetabolite synthesis affected by available nutrient and regulated by autoinducer molecules through quorum sensingmechanism

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 Phylogenetic and Chemical Diversity of a Hybrid-Isoprenoid-Producing Streptomycete Lineage

2013 ◽  
Vol 79 (22) ◽  
pp. 6894-6902 ◽  
Author(s):  
Kelley A. Gallagher ◽  
Kristin Rauscher ◽  
Laura Pavan Ioca ◽  
Paul R. Jensen
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Sequence Data ◽  
Environmental Dna ◽  
Chemical Diversity ◽  
Phenotypic Trait ◽  
Content Type ◽  
Operational Taxonomic Units ◽  
Culture Independent ◽  
Structural Classes

ABSTRACTStreptomycesspecies dedicate a large portion of their genomes to secondary metabolite biosynthesis. A diverse and largely marine-derived lineage within this genus has been designated MAR4 and identified as a prolific source of hybrid isoprenoid (HI) secondary metabolites. These terpenoid-containing compounds are common in nature but rarely observed as bacterial secondary metabolites. To assess the phylogenetic diversity of the MAR4 lineage, complementary culture-based and culture-independent techniques were applied to marine sediment samples collected off the Channel Islands, CA. The results, including those from an analysis of publically available sequence data and strains isolated as part of prior studies, placed 40 new strains in the MAR4 clade, of which 32 originated from marine sources. When combined with sequences cloned from environmental DNA, 28 MAR4 operational taxonomic units (0.01% genetic distance) were identified. Of these, 82% consisted exclusively of either cloned sequences or cultured strains, supporting the complementarity of these two approaches. Chemical analyses of diverse MAR4 strains revealed the production of five different HI structure classes. All 21 MAR4 strains tested produced at least one HI class, with most strains producing from two to four classes. The two major clades within the MAR4 lineage displayed distinct patterns in the structural classes and the number and amount of HIs produced, suggesting a relationship between taxonomy and secondary metabolite production. The production of HI secondary metabolites appears to be a phenotypic trait of the MAR4 lineage, which represents an emerging model with which to study the ecology and evolution of HI biosynthesis.

scholarly journals The Sbi Protein Is a Multifunctional Immune Evasion Factor of Staphylococcus aureus

2011 ◽  
Vol 79 (9) ◽  
pp. 3801-3809 ◽  
Author(s):  
Emma Jane Smith ◽  
Livia Visai ◽  
Steven W. Kerrigan ◽  
Pietro Speziale ◽  
Timothy J. Foster
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Evasion ◽  
Capsular Polysaccharide ◽  
Cell Envelope ◽  
Protein A ◽  
Biologically Active ◽  
Complement Protein ◽  
Content Type ◽  
Binding Domains ◽  
Terminal Domains

ABSTRACTThe second immunoglobulin-binding protein (Sbi) ofStaphylococcus aureushas two N-terminal domains that bind the Fc region of IgG in a fashion similar to that of protein A and two domains that can bind to the complement protein C3 and promote its futile consumption in the fluid phase. It has been proposed that Sbi helps bacteria to avoid innate immune defenses. By comparing a mutant defective in Sbi with mutants defective in protein A, clumping factor A, iron-regulated surface determinant H, and capsular polysaccharide, it was shown that Sbi is indeed an immune evasion factor that promotes bacterial survival in whole human blood and the avoidance of neutrophil-mediated opsonophagocytosis. Sbi is present in the culture supernatant and is also associated with the cell envelope.S. aureusstrains that expressed truncates of Sbi lacking N-terminal domains D1 and D2 (D1D2) or D3 and D4 (D3D4) or a C-terminal truncate that was no longer retained in the cell envelope were analyzed. Both the secreted and envelope-associated forms of Sbi contributed to immune evasion. The IgG-binding domains contributed only when Sbi was attached to the cell, while only the secreted C3-binding domains were biologically active.

scholarly journals EDTA Inhibits Biofilm Formation, Extracellular Vesicular Secretion, and Shedding of the Capsular Polysaccharide Glucuronoxylomannan by Cryptococcus neoformans

2012 ◽  
Vol 78 (22) ◽  
pp. 7977-7984 ◽  
Author(s):  
Emma J. Robertson ◽  
Julie M. Wolf ◽  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Biofilm Formation ◽  
Capsular Polysaccharide ◽  
Inhibitory Effect ◽  
Antifungal Drugs ◽  
Biofilm Growth ◽  
Content Type ◽  
Sublethal Concentrations ◽  
Vesicular Secretion

ABSTRACTThe fungal pathogenCryptococcus neoformanscan grow as a biofilm on a range of synthetic and prosthetic materials. Cryptococcal biofilm formation can complicate the placement of shunts used to relieve increased intracranial pressure in cryptococcal meningitis and can serve as a nidus for chronic infection. Biofilms are generally advantageous to pathogensin vivo, as they can confer resistance to antimicrobial compounds, including fluconazole and voriconazole in the case ofC. neoformans. EDTA can inhibit biofilm formation by several microbes and enhances the susceptibility of biofilms to antifungal drugs. In this study, we evaluated the effect of sublethal concentrations of EDTA on the growth of cryptococcal biofilms. EDTA inhibited biofilm growth byC. neoformans, and the inhibition could be reversed by the addition of magnesium or calcium, implying that the inhibitory effect was by divalent cation starvation. EDTA also reduced the amount of the capsular polysaccharide glucuronoxylomannan shed into the biofilm matrix and decreased vesicular secretion from the cell, thus providing a potential mechanism for the inhibitory effect of this cation-chelating compound. Our data imply that the growth ofC. neoformansbiofilms requires the presence of divalent metals in the growth medium and suggest that cations are required for the export of materials needed for biofilm formation, possibly including extracellular vesicles.

scholarly journals Flagellar Stators Activate a Diguanylate Cyclase To Inhibit Flagellar Stators

2019 ◽  
Vol 201 (18) ◽  
Author(s):  
Daniel B. Kearns
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Secondary Metabolite ◽  
Positive Feedback ◽  
Biofilm Formation ◽  
Feedback Loop ◽  
Diguanylate Cyclase ◽  
Positive Feedback Loop ◽  
Content Type ◽  
Dependent Inhibition

ABSTRACT The bacterial secondary metabolite cyclic di-GMP is a widespread, cytoplasmic signal that promotes a physiological transition in which motility is inhibited and biofilm formation is activated. A paper published in this issue (A. E. Baker, S. S. Webster, A. Diepold, S. L. Kuchma, E. Bordeleau, et al., J Bacteriol 201:e00741-18, 2019, https://doi.org/10.1128/JB.00741-18) makes an important connection between cyclic di-GMP and flagellar components. They show that stator units, which normally interact with the flagellum to power rotation, can alternatively interact with and activate an enzyme that synthesizes cyclic di-GMP in Pseudomonas aeruginosa. Moreover, the same stator units are also the target of cyclic-di-GMP-dependent inhibition such that the more the stators are inhibited, the more cyclic di-GMP is made. The resulting positive-feedback loop not only inhibits motility but also may initiate and stabilize biofilm formation.

scholarly journals Serratia marcescens Quinoprotein Glucose Dehydrogenase Activity Mediates Medium Acidification and Inhibition of Prodigiosin Production by Glucose

2012 ◽  
Vol 78 (17) ◽  
pp. 6225-6235 ◽  
Author(s):  
James E. Fender ◽  
Cody M. Bender ◽  
Nicholas A. Stella ◽  
Roni M. Lahr ◽  
Eric J. Kalivoda ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Serratia Marcescens ◽  
Large Scale ◽  
Transcriptional Control ◽  
Glucose Dehydrogenase ◽  
Model Organism ◽  
Inhibitory Effect ◽  
Biologically Active ◽  
Scale Production ◽  
Content Type

ABSTRACTSerratia marcescensis a model organism for the study of secondary metabolites. The biologically active pigment prodigiosin (2-methyl-3-pentyl-6-methoxyprodiginine), like many other secondary metabolites, is inhibited by growth in glucose-rich medium. Whereas previous studies indicated that this inhibitory effect was pH dependent and did not require cyclic AMP (cAMP), there is no information on the genes involved in mediating this phenomenon. Here we used transposon mutagenesis to identify genes involved in the inhibition of prodigiosin by glucose. Multiple genetic loci involved in quinoprotein glucose dehydrogenase (GDH) activity were found to be required for glucose inhibition of prodigiosin production, including pyrroloquinoline quinone and ubiquinone biosynthetic genes. Upon assessing whether the enzymatic products of GDH activity were involved in the inhibitory effect, we observed thatd-glucono-1,5-lactone andd-gluconic acid, but notd-gluconate, were able to inhibit prodigiosin production. These data support a model in which the oxidation ofd-glucose by quinoprotein GDH initiates a reduction in pH that inhibits prodigiosin production through transcriptional control of the prodigiosin biosynthetic operon, providing new insight into the genetic pathways that control prodigiosin production. Strains generated in this report may be useful in large-scale production of secondary metabolites.

scholarly journals Lysobacter enzymogenes Uses Two Distinct Cell-Cell Signaling Systems for Differential Regulation of Secondary-Metabolite Biosynthesis and Colony Morphology

2013 ◽  
Vol 79 (21) ◽  
pp. 6604-6616 ◽  
Author(s):  
Guoliang Qian ◽  
Yulan Wang ◽  
Yiru Liu ◽  
Feifei Xu ◽  
Ya-Wen He ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Cell Signaling ◽  
Secondary Metabolite ◽  
Colony Morphology ◽  
Content Type ◽  
Signaling Systems ◽  
Lysobacter Enzymogenes ◽  
Bioactive Secondary Metabolites ◽  
Secondary Metabolite Biosynthesis ◽  
First Time

ABSTRACTLysobacter enzymogenesis a ubiquitous environmental bacterium that is emerging as a potentially novel biological control agent and a new source of bioactive secondary metabolites, such as the heat-stable antifungal factor (HSAF) and photoprotective polyene pigments. Thus far, the regulatory mechanism(s) for biosynthesis of these bioactive secondary metabolites remains largely unknown inL. enzymogenes. In the present study, the diffusible signal factor (DSF) and diffusible factor (DF)-mediated cell-cell signaling systems were identified for the first time fromL. enzymogenes. The results show that both Rpf/DSF and DF signaling systems played critical roles in modulating HSAF biosynthesis inL. enzymogenes. Rpf/DSF signaling and DF signaling played negative and positive effects in polyene pigment production, respectively, with DF playing a more important role in regulating this phenotype. Interestingly, only Rpf/DSF, but not the DF signaling system, regulated colony morphology ofL. enzymgenes. Both Rpf/DSF and DF signaling systems were involved in the modulation of expression of genes with diverse functions inL. enzymogenes, and their own regulons exhibited only a few loci that were regulated by both systems. These findings unveil for the first time new roles of the Rpf/DSF and DF signaling systems in secondary metabolite biosynthesis ofL. enzymogenes.

scholarly journals Draft Genome Sequence and Secondary Metabolite Biosynthetic Potential of the Lysobacter niastensis Type Strain DSM 18481

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Paolo Turrini ◽  
Irene Artuso ◽  
Marco Tescari ◽  
Gabriele Andrea Lugli ◽  
Emanuela Frangipani ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Small Molecules ◽  
Secondary Metabolite ◽  
Genome Sequence ◽  
Type Strain ◽  
Draft Genome ◽  
Gene Clusters ◽  
Draft Genome Sequence ◽  
Content Type

ABSTRACT Lysobacter niastensis belongs to a group of bacterial predators that produce a number of bioactive small molecules endowed with lytic properties toward other microorganisms. Here, we report the draft genome sequence of the type strain DSM 18481 and the identification of gene clusters implicated in the biosynthesis of secondary metabolites.

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