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153 Publications visible to you, out of a total of 153
Macroalgal Morphogenesis Induced by Waterborne Compounds and Bacteria in Coastal Seawater

Abstract (Expand)

Axenic gametes of the marine green macroalga Ulva mutabilis Foyn (Ria Formosa, locus typicus) exhibit abnormal development into slow-growing callus-like colonies with aberrant cell walls. Under laboratory … conditions, it was previously demonstrated that all defects in growth and thallus development can be completely abolished when axenic gametes are inoculated with a combination of two specific bacterial strains originally identified as Roseobacter sp. strain MS2 and Cytophaga sp. strain MS6. These bacteria release diffusible morphogenetic compounds (= morphogens), which act similar to cytokinin and auxin. To investigate the ecological relevance of the waterborne bacterial morphogens, seawater samples were collected in the Ria Formosa lagoon (Algarve, Southern Portugal) at 20 sampling sites and tidal pools to assess their morphogenetic effects on the axenic gametes of U. mutabilis. Specifically the survey revealed that sterile-filtered seawater samples can completely recover growth and morphogenesis of U. mutabilis under axenic conditions. Morphogenetic activities of free-living and epiphytic bacteria isolated from the locally very abundant Ulva species (i.e., U. rigida) were screened using a multiwell-based testing system. The most represented genera isolated from U. rigida were Alteromonas, Pseudoalteromonas and Sulfitobacter followed by Psychrobacter and Polaribacter. Several naturally occurring bacterial species could emulate MS2 activity (= induction of cell divisions) regardless of taxonomic affiliation, whereas the MS6 activity (= induction of cell differentiation and cell wall formation) was species-specific and is probably a feature of difficult-to-culture bacteria. Interestingly, isolated bacteroidetes such as Algoriphagus sp. and Polaribacter sp. could individually trigger complete Ulva morphogenesis and thus provide a novel mode of action for bacterial-induced algal development. This study also highlights that the accumulation of algal growth factors in a shallow water body separated from the open ocean by barrier islands might have strong implications to, for example, the wide usage of natural coastal seawater in algal (land based) aquacultures of Ulva.

Authors: J. Grueneberg, A. H. Engelen, R. Costa,

Date Published: 8th Jan 2016

Publication Type: Not specified

Macroalgal-bacterial interactions: identification and role of thallusin in morphogenesis of the seaweed Ulva (Chlorophyta).

Abstract (Expand)

Macroalgal microbiomes have core functions related to biofilm formation, growth, and morphogenesis of seaweeds. In particular, the growth and development of the sea lettuce Ulva spp. (Chlorophyta) … depend on bacteria releasing morphogenetic compounds. Under axenic conditions, the macroalga Ulva mutabilis develops a callus-like phenotype with cell wall protrusions. However, co-culturing with Roseovarius sp. (MS2) and Maribacter sp. (MS6), which produce various stimulatory chemical mediators, completely recovers morphogenesis. This ecological reconstruction forms a tripartite community which can be further studied for its role in cross-kingdom interactions. Hence, our study sought to identify algal growth- and morphogenesis-promoting factors (AGMPFs) capable of phenocopying the activity of Maribacter spp. We performed bioassay-guided solid-phase extraction in water samples collected from U. mutabilis aquaculture systems. We uncovered novel ecophysiological functions of thallusin, a sesquiterpenoid morphogen, identified for the first time in algal aquaculture. Thallusin, released by Maribacter sp., induced rhizoid and cell wall formation at a concentration of 11 pmol l-1. We demonstrated that gametes acquired the iron complex of thallusin, thereby linking morphogenetic processes with intracellular iron homeostasis. Understanding macroalgae-bacteria interactions permits further elucidation of the evolution of multicellularity and cellular differentiation, and development of new applications in microbiome-mediated aquaculture systems.

Authors: T. Alsufyani, G. Califano, M. Deicke, J. Grueneberg, A. Weiss, A. H. Engelen, M. Kwantes, J. F. Mohr, J. F. Ulrich, T. Wichard

Date Published: 11th Jun 2020

Publication Type: Journal

Macroalgal-bacterial interactions: Role of dimethylsulfoniopropionate in microbial gardening by Ulva (Chlorophyta).

Abstract (Expand)

The marine macroalga Ulva mutabilis (Chlorophyta) develops into callus-like colonies consisting of undifferentiated cells and abnormal cell walls under axenic conditions. Ulva mutabilis is routinely … cultured with two bacteria, the Roseovarius sp. MS2 strain and the Maribacter sp. MS6 strain, which release morphogenetic compounds and ensure proper algal morphogenesis. Using this tripartite community as an emerging model system, we tested the hypothesis that the bacterial-algal interactions evolved as a result of mutually taking advantage of signals in the environment. Our study aimed to determine whether cross-kingdom crosstalk is mediated by the attraction of bacteria through algal chemotactic signals. Roseovarius sp. MS2 senses the known osmolyte dimethylsulfoniopropionate (DMSP) released by Ulva into the growth medium. Roseovarius sp. is attracted by DMSP and takes it up rapidly such that DMSP can only be determined in axenic growth media. As DMSP did not promote bacterial growth under the tested conditions, Roseovarius benefited solely from glycerol as the carbon source provided by Ulva. Roseovarius quickly catabolized DMSP into methanethiol (MeSH) and dimethylsulphide (DMS). We conclude that many bacteria can use DMSP as a reliable signal indicating a food source and promote the subsequent development and morphogenesis in Ulva.

Authors: R. W. Kessler, A. Weiss, S. Kuegler, C. Hermes, T. Wichard

Date Published: 2018

Publication Type: Journal

Mechanistic characterization of three sesquiterpene synthases from the termite-associated fungus Termitomyces.

Abstract (Expand)

Three terpene synthases from the termite associated fungus Termitomyces were functionally characterized as (+)-intermedeol synthase, (-)-gamma-cadinene synthase and (+)-germacrene D-4-ol synthase, with … the germacrene D-4-ol synthase as the first reported enzyme that produces the (+)-enantiomer. The enzymatic mechanisms were thoroughly investigated by incubation with isotopically labeled precursors to follow the stereochemical courses of single reaction steps in catalysis. The role of putative active site residues was tested by site directed mutagenesis of a highly conserved tryptophan in all three enzymes and additional residues in (-)-gamma-cadinene synthase that were identified by homology model analysis.

Authors: I. Burkhardt, N. B. Kreuzenbeck, C. Beemelmanns, J. S. Dickschat

Date Published: 27th Mar 2019

Publication Type: Journal

Melleolides from Honey Mushroom Inhibit 5-Lipoxygenase via Cys159.

Abstract (Expand)

5-Lipoxygenase (5-LO) initiates the biosynthesis of pro-inflammatory leukotrienes from arachidonic acid, which requires the nuclear membrane-bound 5-LO-activating protein (FLAP) for substrate transfer. … Here, we identified human 5-LO as a molecular target of melleolides from honey mushroom (Armillaria mellea). Melleolides inhibit 5-LO via an alpha,beta-unsaturated aldehyde serving as Michael acceptor for surface cysteines at the substrate entrance that are revealed as molecular determinants for 5-LO activity. Experiments with 5-LO mutants, where select cysteines had been replaced by serine, indicated that the investigated melleolides suppress 5-LO product formation via two distinct modes of action: (1) by direct interference with 5-LO activity involving two or more of the cysteines 159, 300, 416, and 418, and (2) by preventing 5-LO/FLAP assemblies involving selectively Cys159 in 5-LO. Interestingly, replacement of Cys159 by serine prevented 5-LO/FLAP assemblies as well, implying Cys159 as determinant for 5-LO/FLAP complex formation at the nuclear membrane required for leukotriene biosynthesis.

Authors: S. Konig, E. Romp, V. Krauth, M. Ruhl, M. Dorfer, S. Liening, B. Hofmann, A. K. Hafner, D. Steinhilber, M. Karas, U. Garscha, D. Hoffmeister, O. Werz

Date Published: 17th Jan 2019

Publication Type: Journal

Melleolides impact fungal translation via elongation factor 2.

Abstract (Expand)

Melleolides from the honey mushroom Armillaria mellea represent a structurally diverse group of polyketide-sesquiterpene hybrids. Among various bioactivites, melleolides show antifungal effects against … Aspergillus and other fungi. This bioactivity depends on a Delta2,4-double bond present in dihydroarmillylorsellinate (DAO) or arnamial, for example. Yet, the mode of action of Delta2,4-unsaturated, antifungal melleolides has been unknown. Here, we report on the molecular target of DAO in the fungus Aspergillus nidulans. Using a combination of synthetic chemistry to create a DAO-labelled probe, protein pulldown assays, MALDI-TOF-based peptide analysis and western blotting, we identify the eukaryotic translation elongation factor 2 (eEF2) as a binding partner of DAO. We confirm the inhibition of protein biosynthesis in vivo with an engineered A. nidulans strain producing the red fluorescent protein mCherry. Our work suggests a binding site dissimilar from that of the protein biosynthesis inhibitor sordarin, and highlights translational elongation as a valid antifungal drug target.

Authors: M. Dorfer, D. Heine, S. Konig, S. Gore, O. Werz, C. Hertweck, M. Gressler, D. Hoffmeister

Date Published: 15th May 2019

Publication Type: Journal

Metabolic profiling identifies trehalose as an abundant and diurnally fluctuating metabolite in the microalga Ostreococcus tauri

Abstract (Expand)

INTRODUCTION: The picoeukaryotic alga Ostreococcus tauri (Chlorophyta) belongs to the widespread group of marine prasinophytes. Despite its ecological importance, little is known about the metabolism … of this alga. OBJECTIVES: In this work, changes in the metabolome were quantified when O. tauri was grown under alternating cycles of 12 h light and 12 h darkness. METHODS: Algal metabolism was analyzed by gas chromatography-mass spectrometry. Using fluorescence-activated cell sorting, the bacteria associated with O. tauri were depleted to below 0.1% of total cells at the time of metabolic profiling. RESULTS: Of 111 metabolites quantified over light-dark cycles, 20 (18%) showed clear diurnal variations. The strongest fluctuations were found for trehalose. With an intracellular concentration of 1.6 mM in the dark, this disaccharide was six times more abundant at night than during the day. This fluctuation pattern of trehalose may be a consequence of starch degradation or of the synchronized cell cycle. On the other hand, maltose (and also sucrose) was below the detection limit (~10 muM). Accumulation of glycine in the light is in agreement with the presence of a classical glycolate pathway of photorespiration. We also provide evidence for the presence of fatty acid methyl and ethyl esters in O. tauri. CONCLUSIONS: This study shows how the metabolism of O. tauri adapts to day and night and gives new insights into the configuration of the carbon metabolism. In addition, several less common metabolites were identified.

Authors: M. Hirth, S. Liverani, S. Mahlow, F. Y. Bouget, G. Pohnert, S. Sasso

Date Published: No date defined

Publication Type: Not specified

Metabolomic compounds identified in Piriformospora indica-colonized Chinese cabbage roots delineate symbiotic functions of the interaction

Abstract (Expand)

Root colonization by endophytic fungus Piriformospora indica facilitating growth/development and stress tolerance has been demonstrated in various host plants. However, global metabolomic studies are … rare. By using high-throughput gas-chromatography-based mass spectrometry, 549 metabolites of 1,126 total compounds observed were identified in colonized and uncolonized Chinese cabbage roots, and hyphae of P. indica. The analyses demonstrate that the host metabolomic compounds and metabolite pathways are globally reprogrammed after symbiosis with P. indica. Especially, γ-amino butyrate (GABA), oxylipin-family compounds, poly-saturated fatty acids, and auxin and its intermediates were highly induced and de novo synthesized in colonized roots. Conversely, nicotinic acid (niacin) and dimethylallylpyrophosphate were strongly decreased. In vivo assays with exogenously applied compounds confirmed that GABA primes plant immunity toward pathogen attack and enhances high salinity and temperature tolerance. Moreover, generation of reactive oxygen/nitrogen species stimulated by nicotinic acid is repressed by P. indica, and causes the feasibility of symbiotic interaction. This global metabolomic analysis and the identification of symbiosis-specific metabolites may help to understand how P. indica confers benefits to the host plant.

Authors: Mo Da-Sang Hua, Rajendran Senthil Kumar, Lie-Fen Shyur, Yuan-Bin Cheng, Zhihong Tian, Ralf Oelmüller, Kai-Wun Yeh

Date Published: 24th Aug 2017

Publication Type: Not specified

Metallophore profiling of nitrogen-fixing Frankia spp. to understand metal management in the rhizosphere of actinorhizal plants.

Abstract (Expand)

Frankia spp. are widespread nitrogen-fixing soil bacteria, which often live in symbiosis with a broad range of hosts. Metal homeostasis plays a crucial role in the success of the symbiosis regarding … the acquisition of essential trace metals and detoxification of potentially toxic elements. We have hypothesised that Frankia releases many organic ligands with a broad spectrum of affinity for essential and toxic metals. We coined the term 'ligandosphere' to describe the entirety of excreted metal complexing agents and ligands derived from the dissolved organic matter. Using metal isotope-coded profiling (MICP); metallophores of physiological important and toxic trace metals were identified by the addition of stable metal isotope pairs such as 54Fe/58Fe, 63Cu/65Cu, 66Zn/68Zn or 95Mo/98Mo. Liquid chromatography coupled to a mass spectrometer revealed strong variations of the metallophore profile in between the 14 test-strains. In total, about 83 organic ligands were identified as binding to one of the tested metals. The predicted sum formula of the major Fe binding ligands and MS/MS experiments suggested that several metallophore candidates have a similar molecular backbone. Growth experiments with a hyper-producer of metallophores revealed a positive relationship between metallophore production and the concentration of Cu in the growth medium. The present study provides the first comprehensive overview of the complexity of Frankia's ligandosphere. It opens a path to a deeper understanding of mechanisms that regulate metal homeostasis in frankiae. Deciphering these mechanisms is important since the fitness of actinorhizal plants and their potential in ecological restoration relies heavily on their symbiosis with frankiae.

Authors: M. Deicke, J. F. Mohr, S. Roy, P. Herzsprung, J. P. Bellenger, T. Wichard

Date Published: 17th Apr 2019

Publication Type: Journal

Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters

Abstract (Expand)

Microorganisms form diverse multispecies communities in various ecosystems. The high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms. … A key role in this communication is played by secondary metabolites (SMs), which are also called natural products. Recently, it was shown that interspecies "talk" between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel SMs by the involved species. This review focuses on mixed microbial cultivation, mainly between bacteria and fungi, with a special emphasis on the induced formation of fungal SMs in co-cultures. In addition, the role of chromatin remodeling in the induction is examined, and methodical perspectives for the analysis of natural products are presented. As an example for an intermicrobial interaction elucidated at the molecular level, we discuss the specific interaction between the filamentous fungi Aspergillus nidulans and Aspergillus fumigatus with the soil bacterium Streptomyces rapamycinicus, which provides an excellent model system to enlighten molecular concepts behind regulatory mechanisms and will pave the way to a novel avenue of drug discovery through targeted activation of silent SM gene clusters through co-cultivations of microorganisms.

Authors: , J. Fischer, J. Weber, D. J. Mattern, C. C. Konig, V. Valiante, ,

Date Published: 20th Apr 2015

Publication Type: Not specified

Microbial communities in carbonate rocks-from soil via groundwater to rocks.

Abstract (Expand)

Microbial communities in soil, groundwater, and rock of two sites in limestone were investigated to determine community parameters differentiating habitats in two lithostratigraphic untis. Lower … Muschelkalk and Middle Muschelkalk associated soils, groundwater, and rock samples showed different, but overlapping microbial communities linked to carbon fluxes. The microbial diversities in soil were highest, groundwater revealed overlapping taxa but lower diversity, and rock samples were predominantly characterized by endospore forming bacteria and few archaea. Physiological profiles could establish a differentiation between habitats (soil, groundwater, rock). From community analyses and physiological profiles, different element cycles in limestone could be identified for the three habitats. While in soil, nitrogen cycling was identified as specific determinant, in rock methanogenesis linked carbonate rock to atmospheric methane cycles. These patterns specifically allowed for delineation of lithostratigraphic connections to physiological parameters.

Authors: A. Meier, M. K. Singh, A. Kastner, D. Merten, G. Buchel, E. Kothe

Date Published: 7th Jul 2017

Publication Type: Not specified

Mind the mushroom: natural product biosynthetic genes and enzymes of Basidiomycota.

Abstract (Expand)

Covering: up to September 2020 Mushroom-forming fungi of the division Basidiomycota have traditionally been recognised as prolific producers of structurally diverse and often bioactive secondary … metabolites, using the methods of chemistry for research. Over the past decade, -omics technologies were applied on these fungi, and sophisticated heterologous gene expression platforms emerged, which have boosted research into the genetic and biochemical basis of the biosyntheses. This review provides an overview on experimentally confirmed natural product biosyntheses of basidiomycete polyketides, amino acid-derived products, terpenoids, and volatiles. We also present challenges and solutions particular to natural product research with these fungi. 222 references are cited.

Authors: M. Gressler, N. A. Lohr, T. Schafer, S. Lawrinowitz, P. S. Seibold, D. Hoffmeister

Date Published: 28th Apr 2021

Publication Type: Journal

Mining and unearthing hidden biosynthetic potential.

Abstract (Expand)

Genetically encoded small molecules (secondary metabolites) play eminent roles in ecological interactions, as pathogenicity factors and as drug leads. Yet, these chemical mediators often evade detection, … and the discovery of novel entities is hampered by low production and high rediscovery rates. These limitations may be addressed by genome mining for biosynthetic gene clusters, thereby unveiling cryptic metabolic potential. The development of sophisticated data mining methods and genetic and analytical tools has enabled the discovery of an impressive array of previously overlooked natural products. This review shows the newest developments in the field, highlighting compound discovery from unconventional sources and microbiomes.

Authors: K. Scherlach, C. Hertweck

Date Published: 23rd Jun 2021

Publication Type: Journal

Mining Symbionts of a Spider-Transmitted Fungus Illuminates Uncharted Biosynthetic Pathways to Cytotoxic Benzolactones

Abstract (Expand)

A spider-transmitted fungus (Rhizopus microspo- rus) that was isolated from necrotic human tissue was found to harbor endofungal bacteria (Burkholderia sp.). Metabolic profiling of the symbionts revealed … a complex of cytotoxic agents (necroximes). Their structures were characterized as oxime-substituted benzolactone enamides with a peptidic side chain. The potently cytotoxic necroximes are also formed in symbiosis with the fungal host and could have contributed to the necrosis. Genome sequencing and computational analyses revealed a novel modular PKS/NRPS assembly line equipped with several non-canonical domains. Based on gene-deletion mutants, we propose a biosynthetic model for bacterial benzolactones. We identified specific traits that serve as genetic handles to find related salicylate macrolide pathways (lobata- mide, oximidine, apicularen) in various other bacterial genera. Knowledge of the biosynthetic pathway enables biosynthetic engineering and genome-mining approaches.

Authors: Sarah Niehs, Benjamin Dose, Sophie Richter, Sacha J. Pidot, Timothy P. Stinear, Hans-Martin Dahse, Christian Hertweck

Date Published: 10th Feb 2020

Publication Type: Not specified

Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy

Abstract (Expand)

Tumour-associated macrophages mainly comprise immunosuppressive M2 phenotypes that promote tumour progression besides anti-tumoural M1 subsets. Selective depletion or reprogramming of M2 may represent … an innovative anti-cancer strategy. The actin cytoskeleton is central for cellular homeostasis and is targeted for anti-cancer chemotherapy. Here, we show that targeting G-actin nucleation using chondramide A (ChA) predominantly depletes human M2 while promoting the tumour-suppressive M1 phenotype. ChA reduced the viability of M2, with minor effects on M1, but increased tumour necrosis factor (TNF)alpha release from M1. Interestingly, ChA caused rapid disruption of dynamic F-actin filaments and polymerization of G-actin, followed by reduction of cell size, binucleation and cell division, without cellular collapse. In M1, but not in M2, ChA caused marked activation of SAPK/JNK and NFkappaB, with slight or no effects on Akt, STAT-1/-3, ERK-1/2, and p38 MAPK, seemingly accounting for the better survival of M1 and TNFalpha secretion. In a microfluidically-supported human tumour biochip model, circulating ChA-treated M1 markedly reduced tumour cell viability through enhanced release of TNFalpha. Together, ChA may cause an anti-tumoural microenvironment by depletion of M2 and activation of M1, suggesting induction of G-actin nucleation as potential strategy to target tumour-associated macrophages in addition to neoplastic cells.

Authors: C. Pergola, K. Schubert, S. Pace, J. Ziereisen, F. Nikels, O. Scherer, S. Huttel, S. Zahler, A. M. Vollmar, C. Weinigel, S. Rummler, R. Muller, M. Raasch, A. Mosig, A. Koeberle, O. Werz

Date Published: 31st Jan 2017

Publication Type: Not specified

Morphogenesis of Ulva mutabilis (Chlorophyta) induced by Maribacter species (Bacteroidetes, Flavobacteriaceae)

Abstract (Expand)

Growth and morphogenesis of the sea lettuce Ulva (Chlorophyta) depends on the combination of regulative morphogenetic compounds released by specific associated bacteria. Axenic Ulva gametes develop … parthenogenetically into callus-like colonies consisting of undifferentiated cells without normal cell walls. In Ulva mutabilis Føyn, two bacterial strains, Maribacter sp. strain MS6 and Roseovarius strain MS2, can restore the complete algal morphogenesis forming a tripartite symbiotic community. Morphogenetic compounds (=morphogens) released by the MS6-strain induce rhizoid formation and cell wall development in U. mutabilis, while several bacteria of the Roseobacter clade, including the MS2-strain, promote blade cell division and thallus elongation. In this study, 12 type strains of the Flavobacteriaceae family, including six Maribacter strains, were examined for their morphogenetic activity in comparison to the original MS6-strain isolated from U. mutabilis. The bioassay is based on the functional complementation of the tested Flavobacteriaceae strain with the Roseovarius MS2-strain. If the test-strain possesses morphogenetic activity complementary to the factor of the MS2-strain, the complete morphogenesis of U. mutabilis can be restored. This bioassay revealed not only the stand-alone activity of certain bacteria, but also their essential capability to take part in the orchestrated bacteria-induced morphogenesis of U. mutabilis. All Maribacter type strains isolated from Ulva could phenocopy the MS6-strain, whereas some distantly related Flavobacteriaceae and a Maribacter strain isolated from a red alga did not possess any activity. Keywords: bacteroidetes; cell differentiation; green macroalga; morphogens; thallusin

Authors: Thomas Wichard, Anne Weiss, R. Costa

Date Published: No date defined

Publication Type: Not specified

Multimodal Molecular Imaging and Identification of Bacterial Toxins Causing Mushroom Soft Rot and Cavity Disease

Abstract (Expand)

Soft rot disease of edible mushrooms leads to rapid degeneration of fungal tissue and thus severely affects farming productivity worldwide. The bacterial mushroom pathogen Burkholderia gladioli pv. … agaricicola has been identified as the cause. Yet, little is known about the molecular basis, the spatial distribution and the biological role of antifungal agents and toxins involved in this infectious disease. We combine genome mining, metabolic profiling, MALDI-Imaging and UV Raman spectroscopy, to detect, identify and visualize a complex of chemical mediators and toxins produced by the pathogen during the infection process, including toxoflavin, caryoynencin, and sinapigladioside. Furthermore, targeted gene knockouts and in vitro assays link antifungal agents to prevalent symptoms of soft rot, mushroom browning, and impaired mycelium growth. Comparisons of related pathogenic, mutualistic and environmental Burkholderia spp. indicate that the arsenal of antifungal agents may have paved the way for ancestral bacteria to colonize niches where frequent, antagonistic interactions with fungi occur. Our findings not only demonstrate the power of label-free, in vivo detection of polyyne virulence factors by Raman imaging, but may also inspire new approaches to disease control.

Authors: Benjamin Dose, Tawatchai Thongkongkaew, David Zopf, Hak Joong Kim, Evgeni V. Bratovanov, María García-Altares Pérez, Kirstin Scherlach, Jana Krabbe, Claudia Ross, Ron Hermenau, Sarah P. Niehs, Anja Silge, Julian Hniopek, Michael Schmitt, Jürgen Popp, Christian Hertweck

Date Published: 7th Jul 2021

Publication Type: Journal

Multimodular type I polyketide synthases in algae evolve by module duplications and displacement of AT domains in trans

Abstract (Expand)

BACKGROUND: Polyketide synthase (PKS) catalyzes the biosynthesis of polyketides, which are structurally and functionally diverse natural products in microorganisms and plants. Here, we have analyzed … available full genome sequences of microscopic and macroscopic algae for the presence of type I PKS genes. RESULTS: Type I PKS genes are present in 15 of 32 analyzed algal species. In chlorophytes, large proteins in the MDa range are predicted in most sequenced species, and PKSs with free-standing acyltransferase domains (trans-AT PKSs) predominate. In a phylogenetic tree, PKS sequences from different algal phyla form clades that are distinct from PKSs from other organisms such as non-photosynthetic protists or cyanobacteria. However, intermixing is observed in some cases, for example polyunsaturated fatty acid (PUFA) and glycolipid synthases of various origins. Close relationships between type I PKS modules from different species or between modules within the same multimodular enzyme were identified, suggesting module duplications during evolution of algal PKSs. In contrast to type I PKSs, nonribosomal peptide synthetases (NRPSs) are relatively rare in algae (occurrence in 7 of 32 species). CONCLUSIONS: Our phylogenetic analysis of type I PKSs in algae supports an evolutionary scenario whereby integrated AT domains were displaced to yield trans-AT PKSs. Together with module duplications, the displacement of AT domains may constitute a major mechanism of PKS evolution in algae. This study advances our understanding of the diversity of eukaryotic PKSs and their evolutionary trajectories.

Authors: , N. Heimerl, M. Fichtner,

Date Published: 26th Nov 2015

Publication Type: Not specified

Myxochelin-Inspired 5-Lipoxygenase Inhibitors: Synthesis and Biological Evaluation

Abstract (Expand)

A total of 48 analogues of the natural product myxochelin A were prepared and evaluated for their inhibitory effects on human 5-lipoxygenase in both cell-free and cell-based assays. Structure-activity … relationship analysis revealed that the secondary alcohol function and only chiral center of myxochelin A is not required for biological activity. By expanding the diaminoalkane linker of the two aromatic residues it was possible to generate a myxochelin derivative with superior activity against 5-lipoxygenase in intact cells.

Authors: S. Schieferdecker, S. Konig, S. Pace, O. Werz, M. Nett

Date Published: 23rd Nov 2016

Publication Type: Not specified

Myxochelins target human 5-lipoxygenase

Abstract (Expand)

Extracts of the predatory myxobacterium Pyxidicoccus fallax HKI 727 showed antiproliferative effects on leukemic K-562 cells. Bioactivity-guided fractionation led to the isolation of the bis-catechol … myxochelin A and two new congeners. The biosynthetic origin of myxochelins C and D was confirmed by feeding studies with isotopically labeled precursors. Pharmacological testing revealed human 5-lipoxygenase (5-LO) as a molecular target of the myxochelins. In particular, myxochelin A efficiently inhibited 5-LO activity with an IC50 of 1.9 muM and reduced the proliferation of K-562 cells at similar concentrations.

Authors: S. Schieferdecker, S. Konig, , H. M. Dahse, ,

Date Published: 16th Feb 2015

Publication Type: Not specified

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