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23 Publications visible to you, out of a total of 23
Biosynthesis of Sinapigladioside, an Antifungal Isothiocyanate from Burkholderia Symbionts.

Abstract (Expand)

Sinapigladioside is a rare isothiocyanate-bearing natural product from beetle-associated bacteria ( Burkholderia gladioli ) that may protect the beetle offspring against entomopathogenic fungi. The … biosynthetic origin of sinapigladioside has been elusive, and little is known about bacterial isothiocyanate biosynthesis in general. On the basis of stable-isotope labeling, bioinformatics, and mutagenesis we identified the sinapigladioside biosynthesis gene cluster in the symbiont and found that an isonitrile synthase plays a key role in the biosynthetic pathway. Genome mining and network analyses indicate that related gene clusters are distributed across various bacterial phyla including producers of both nitriles and isothiocyanates. Our findings support a model for bacterial isothiocyanate biosynthesis by sulfur transfer onto isonitrile precursors.

Authors: B. Dose, S. P. Niehs, K. Scherlach, S. Shahda, L. V. Florez, M. Kaltenpoth, C. Hertweck

Date Published: 19th Mar 2021

Publication Type: Journal

Lipopeptide-mediated bacterial interaction enables cooperative predator defense

Abstract (Expand)

Bacteria are inherently social organisms whose actions should ideally be studied within an interactive ecological context. We show that the exchange and modification of natural products enables two … unrelated bacteria to defend themselves against a common predator. Amoebal predation is a major cause of death in soil bacteria and thus it exerts a trong selective pressure to evolve defensive strategies. A systematic analysis of binary combinations of coisolated bacteria revealed strains that were individually susceptible to predation but together killed their predator. This cooperative defense relies on a Pseudomonas species producing syringafactin, a lipopeptide, which induces the production of peptidases in a Paenibacillus strain. These peptidases then degrade the innocuous syringafactin into compounds, which kill the predator. A combination of bioprospecting, coculture experiments, genome modification, and transcriptomics unravel this novel natural product-based defense strategy.

Authors: Shuaibing Zhang, Ruchira Mukherji, Somak Chowdhury, Lisa Reimer, Pierre Stallforth

Date Published: 1st Feb 2021

Publication Type: Journal

Helper bacteria halt and disarm mushroom pathogens by linearizing structurally diverse cyclolipopeptides.

Abstract (Expand)

The bacterial pathogen Pseudomonas tolaasii severely damages white button mushrooms by secretion of the pore-forming toxin tolaasin, the main virulence factor of brown blotch disease. Yet, fungus-associated … helper bacteria of the genus Mycetocola (Mycetocola tolaasinivorans and Mycetocola lacteus) may protect their host by an unknown detoxification mechanism. By a combination of metabolic profiling, imaging mass spectrometry, structure elucidation, and bioassays, we found that the helper bacteria inactivate tolaasin by linearizing the lipocyclopeptide. Furthermore, we found that Mycetocola spp. impair the dissemination of the pathogen by cleavage of the lactone ring of pseudodesmin. The role of pseudodesmin as a major swarming factor was corroborated by identification and inactivation of the corresponding biosynthetic gene cluster. Activity-guided fractionation of the Mycetocola proteome, matrix-assisted laser desorption/ionization (MALDI) analyses, and heterologous enzyme production identified the lactonase responsible for toxin cleavage. We revealed an antivirulence strategy in the context of a tripartite interaction that has high ecological and agricultural relevance.

Authors: R. Hermenau, S. Kugel, A. J. Komor, C. Hertweck

Date Published: 31st Aug 2020

Publication Type: Not specified

Food-Poisoning Bacteria Employ a Citrate Synthase and a Type II NRPS To Synthesize Bolaamphiphilic Lipopeptide Antibiotics.

Abstract (Expand)

Mining the genome of the food-spoiling bacterium Burkholderia gladioli pv. cocovenenans revealed five nonribosomal peptide synthetase (NRPS) gene clusters, including an orphan gene locus (bol). Gene … inactivation and metabolic profiling linked the bol gene cluster to novel bolaamphiphilic lipopeptides with antimycobacterial activity. A combination of chemical analysis and bioinformatics elucidated the structures of bolagladin A and B, lipocyclopeptides featuring an unusual dehydro-beta-alanine enamide linker fused to an unprecedented tricarboxylic fatty acid tail. Through a series of targeted gene deletions, we proved the involvement of a designated citrate synthase (CS), priming ketosynthases III (KS III), a type II NRPS, including a novel desaturase for enamide formation, and a multimodular NRPS in generating the cyclopeptide. Network analyses revealed the evolutionary origin of the CS and identified cryptic CS/NRPS gene loci in various bacterial genomes.

Authors: B. Dose, C. Ross, S. P. Niehs, K. Scherlach, J. P. Bauer, C. Hertweck

Date Published: 11th Aug 2020

Publication Type: Not specified

Insect-Associated Bacteria Assemble the Antifungal Butenolide Gladiofungin by Non-Canonical Polyketide Chain Termination.

Abstract (Expand)

Genome mining of one of the protective symbionts ( Burkholderia gladioli ) of the invasive beetle Lagria villosa revealed a cryptic gene cluster coding for the biosynthesis of a novel antifungal … polyketide with a glutarimide pharmacophore. Targeted gene inactivation, metabolic profiling and bioassays led to the discovery of the gladiofungins as yet overlooked components of the antimicrobial armory of the beetle symbiont, specifically against the entomopathogenic fungus Purpureocillium lilacinum . By mutational analyses, isotope labeling and in silico analyses of the modular polyketide synthase, we found that the rare butenolide moiety of gladiofungins derives from an unprecedented polyketide chain termination reaction involving a glycerol-derived C3 building block. The key role of an A-factor synthase (AfsA)-like offloading domain was corroborated by CRISPR-Cas-mediated gene editing, which facilitated the precise excision within a PKS domain.

Authors: S. P. Niehs, J. Kumpfmuller, B. Dose, R. F. Little, K. Ishida, L. V. Florez, M. Kaltenpoth, C. Hertweck

Date Published: 26th Jun 2020

Publication Type: Not specified

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

Genome Mining Reveals Endopyrroles from a Nonribosomal Peptide Assembly Line Triggered in Fungal-Bacterial Symbiosis

Abstract (Expand)

The bacterial endosymbiont (Burkholderia rhizoxinica) of the rice seedling blight fungus (Rhizopus microsporus) harbors a large number of cryptic biosynthesis gene clusters. Genome mining and sequence … similarity networks based on an encoded nonribosomal peptide assembly line and the associated pyrrole- forming enzymes in the symbiont indicated that the encoded metabolites are unique among a large number of tentative pyrrole natural products in diverse and unrelated bacterial phyla. By performing comparative metabolic pro fi ling using a mutant generated with an improved pheS Burkholderia counterselection marker, we found that the symbionts ’ biosynthetic pathway is mainly activated under salt stress and exclusively in symbiosis with the fungal host. The cryptic metabolites were fully characterized as novel pyrrole-substituted depsipeptides (endopyrroles). A broader survey showed that endopyrrole production is a hallmark of geographically distant endofungal bacteria, which produce the peptides solely under symbiotic conditions.

Authors: Sarah Niehs, Benjamin Dose, Kirstin Scherlach, Sacha J. Pidot, Timothy P. Stinear, Christian Hertweck

Date Published: 8th Jul 2019

Publication Type: Not specified

Genomics-driven discovery of a linear lipopeptide promoting host colonization by endofungal bacteria

Abstract (Expand)

The rice seedling blight fungus Rhizopus microsporus weakens or kills plants by means of a potent toxin produced by endobacteria (Burkholderia rhizoxinica) that live within the fungal hyphae. The success … of the highly attuned microbial interaction is partly based on the bacteria ’ s ability to roam and re-colonize the fungal host. Yet, apart from the toxin, chemical mediators of the symbiosis have remained elusive. By genome mining and comparison we identi fi ed a cryptic NRPS gene cluster that is conserved among all sequenced Rhizopus endosymbionts. Metabolic pro fi ling and targeted gene inactivation led to the discov- ery of a novel linear lipopeptide, holrhizin A, which was fully characterized. Through in vitro and in vivo assays we found that holrhizin acts (A) as a biosurfactant to reduce surface tension, (B) in fl uences the for- mation of mature bio fi lms and thus cell motility behavior that ultimately supports the bacterial cells to (C) colonize and invade the fungal host, consequently supporting the re-establishment of the exceptional Burkholderia-Rhizopus symbiosis. We not only unveil structure and function of an linear lipopeptide from endofungal bacteria but also provide a functional link between the symbiont’ s orphan NRPS genes and a chemical mediator that promotes bacterial invasion into the fungal host.

Authors: Sarah Niehs, Kirstin Scherlach, Christian Hertweck

Date Published: 31st Aug 2018

Publication Type: Not specified

Unexpected Bacterial Origin of the Antibiotic Icosalide Two-Tailed Depsipeptide Assembly in Multifarious Burkholderia Symbionts

Abstract (Expand)

Icosalide is an unusual two-tailed lipocyclopeptide antibiotic that was originally isolated from a fungal culture. Yet, its biosynthesis and ecological function have remained enigmatic. By genome mining …g and metabolic pro fi ling of a bacterial endosymbiont (Burkholderia gladioli) of the pest beetle Lagria villosa, we unveiled a bacterial origin of icosalide. Functional analysis of the biosynthetic gene locus revealed an unprecedented nonribosomal peptide synthetase (NRPS) that incorporates two β -hydroxy acids by means of two starter condensation domains in di ff erent modules. This unusual assembly line, which may inspire new synthetic biology approaches, is widespread among many symbiotic Burkholderia species from diverse habitats. Biological assays showed that icosalide is active against entomopathogenic bacteria, thus adding to the chemical armory protecting beetle offspring. By creating a null mutant, we found that icosalide is a swarming inhibitor, which may play a role in symbiotic interactions and bears the potential for therapeutic applications.

Authors: Benjamin Dose, Sarah Niehs, Kirstin Scherlach, Laura V. Florez, Martin Kaltenpoth, Christian Hertweck

Date Published: 30th Aug 2018

Publication Type: Not specified

Genomics-Driven Discovery of a Symbiont-Specific Cyclopeptide from Bacteria Residing in the Rice Seedling Blight Fungus

Abstract (Expand)

The rice seedling blight fungus Rhizopus microsporus harbors endosymbiotic bacteria (Burkholderia rhizoxinica) that produce the virulence factor rhizoxin and control host development. Genome mining … indicated a massive inventory of cryptic non- ribosomal peptide synthetase (NRPS) genes, which have not yet been linked to any natural products. The discovery and full characterization of a novel cyclopeptide from endofungal bac- teria is reported. In silico analysis of an orphan, symbiont-spe- cific NRPS predicted the structure of a nonribosomal peptide, which was targeted by LC-MS/MS profiling of wild-type and engineered null mutants. NMR spectroscopy and chemical deri- vatization elucidated the structure of the bacterial cyclopep- tide. Phylogenetic analyses revealed the relationship of starter C domains for rare N-acetyl-capped peptides. Heptarhizin is produced under symbiotic conditions in geographically con- strained strains from the Pacific clade; this indicates a potential ecological role of the peptide.

Authors: Sarah Niehs, Benjamin Dose, Kirstin Scherlach, Martin Roth, Christian Hertweck

Date Published: 16th Aug 2018

Publication Type: Not specified

Antibiotic-producing symbionts dynamically transition between plant pathogenicity and insect-defensive mutualism

Abstract (Expand)

Pathogenic and mutualistic bacteria associated with eukaryotic hosts often lack distinctive genomic features, suggesting regular transitions between these lifestyles. Here we present evidence supporting … a dynamic transition from plant pathogenicity to insect-defensive mutualism in symbiotic Burkholderia gladioli bacteria. In a group of herbivorous beetles, these symbionts protect the vulnerable egg stage against detrimental microbes. The production of a blend of antibiotics by B. gladioli, including toxoflavin, caryoynencin and two new antimicrobial compounds, the macrolide lagriene and the isothiocyanate sinapigladioside, likely mediate this defensive role. In addition to vertical transmission, these insect symbionts can be exchanged via the host plant and retain the ability to initiate systemic plant infection at the expense of the plant's fitness. Our findings provide a paradigm for the transition between pathogenic and mutualistic lifestyles and shed light on the evolution and chemical ecology of this defensive mutualism.

Authors: L. V. Florez, K. Scherlach, P. Gaube, C. Ross, E. Sitte, C. Hermes, A. Rodrigues, C. Hertweck, M. Kaltenpoth

Date Published: 30th Apr 2017

Publication Type: Not specified

JA-Ile-macrolactones uncouple growth and defense in wild tobacco

Abstract (Expand)

Small molecules capable of uncoupling growth-defense in plants are currently not known. In this study, for the first time, semi-synthetic analogues of the phytohormone JA-Ile are employed to uncouple … growth and defense responses in wild tobacco. The JA-Ile analogues are easily synthesized from inexpensive substrates via olefin metathesis.

Authors: G. H. Jimenez-Aleman, R. A. R. Machado, I. T. Baldwin, W. Boland

Date Published: 7th Mar 2017

Publication Type: Not specified

Evaluation of Dual 5-Lipoxygenase/Microsomal Prostaglandin E2 Synthase-1 Inhibitory Effect of Natural and Synthetic Acronychia-Type Isoprenylated Acetophenones

Abstract (Expand)

Among the pathways responsible for the development of inflammatory responses, the cyclooxygenase and lipoxygenase pathways are among the most important ones. Two key enzymes, namely, 5-LO and mPGES-1, … are involved in the biosynthesis of leukotrienes and prostaglandins, respectively, which are considered attractive therapeutic targets, so their dual inhibition might be an effective strategy to control inflammatory deregulation. Several natural products have been identified as 5-LO inhibitors, with some also being dual 5-LO/mPGES-1 inhibitors. Here, some prenylated acetophenone dimers from Acronychia pedunculata have been identified for their dual inhibitory potency toward 5-LO and mPGES-1. To gain insight into the SAR of this family of natural products, the synthesis and biological evaluation of analogues are presented. The results show the ability of the natural and synthetic molecules to potently inhibit 5-LO and mPEGS-1 in vitro. The potency of the most active compound (10) has been evaluated in vivo in an acute inflammatory mouse model and displayed potent anti-inflammatory activity comparable in potency to the drug zileuton used as a positive control.

Authors: A. Svouraki, U. Garscha, E. Kouloura, S. Pace, C. Pergola, V. Krauth, A. Rossi, L. Sautebin, M. Halabalaki, O. Werz, N. Gaboriaud-Kolar, A. L. Skaltsounis

Date Published: 28th Feb 2017

Publication Type: Not specified

Sticking together: inter-species aggregation of bacteria isolated from iron snow is controlled by chemical signaling

Abstract (Expand)

Marine and lake snow is a continuous shower of mixed organic and inorganic aggregates falling from the upper water where primary production is substantial. These pelagic aggregates provide a niche for … microbes that can exploit these physical structures and resources for growth, thus are local hot spots for microbial activity. However, processes underlying their formation remain unknown. Here, we investigated the role of chemical signaling between two co-occurring bacteria that each make up more than 10% of the community in iron-rich lakes aggregates (iron snow). The filamentous iron-oxidizing Acidithrix strain showed increased rates of Fe(II) oxidation when incubated with cell-free supernatant of the heterotrophic iron-reducing Acidiphilium strain. Amendment of Acidithrix supernatant to motile cells of Acidiphilium triggered formation of cell aggregates displaying similar morphology to those of iron snow. Comparative metabolomics enabled the identification of the aggregation-inducing signal, 2-phenethylamine, which also induced faster growth of Acidiphilium. We propose a model that shows rapid iron snow formation, and ultimately energy transfer from the photic zone to deeper water layers, is controlled via a chemically mediated interplay.

Authors: J. F. Mori, N. Ueberschaar, S. Lu, R. E. Cooper, G. Pohnert, K. Kusel

Date Published: 1st Feb 2017

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

Symbiont-Derived Antimicrobials Contribute to the Control of the Lepidopteran Gut Microbiota

Abstract (Expand)

Insects develop efficient antimicrobial strategies to flourish in a bacterial world. It has long been proposed that native gut microbiota is an important component of host defense; however, the responsible … species have rarely been isolated to elucidate the mechanism of action. Here we show that the dominant symbiotic bacterium Enterococcus mundtii associated with the generalist herbivore Spodoptera littoralis actively secretes a stable class IIa bacteriocin (mundticin KS) against invading bacteria, but not against other gut residents, facilitating the normal development of host gut microbiota. A mundticin-defective strain lost inhibitory activity. Furthermore, purified mundticin cures infected larvae. Thus, the constitutively produced antimicrobials by native extracellular symbionts create a significant chemical barrier inside limiting invader expansion. This unique property also benefits E. mundtii itself by providing a competitive advantage, contributing to its dominance within complex microbial settings and its prevalence across Lepidoptera, and probably promotes the long-term cooperative symbiosis between both parties.

Authors: Y. Shao, B. Chen, C. Sun, K. Ishida, C. Hertweck, W. Boland

Date Published: 21st Jan 2017

Publication Type: Not specified

Biophysical characterization and antineoplastic activity of new bis(thiosemicarbazonato) Cu(II) complexes

Abstract (Expand)

Aiming to explore alternative mechanisms of cellular uptake and cytotoxicity, we have studied a new family of copper(II) complexes (CuL1-CuL4) with bis(thiosemicarbazone) (BTSC) ligands containing … pendant protonable cyclic amines (morpholine and piperidine). Herein, we report on the synthesis and characterization of these new complexes, as well as on their biological performance (cytotoxic activity, cellular uptake, protein and DNA binding), in comparison with the parental CuIIATSM (ATSM=diacetyl-bis(N4-methylthiosemicarbazonate) complex without pendant cyclic amines. The new compounds have been characterized by a range of analytical techniques including ESI-MS, IR spectroscopy, cyclic voltammetry, reverse-phase HPLC and X-ray spectroscopy. In vitro cytotoxicity studies revealed that the copper complexes are cytotoxic, unlike the corresponding ligands, with a similar potency to that of CuATSM. Unlike CuATSM, the new complexes were able to circumvent cisplatin cross-resistance. The presence of the protonable cyclic amines did not lead to an enhancement of the interaction of the complexes with human serum albumin or calf thymus DNA. However, CuL1-CuL4 showed a remarkably augmented cellular uptake compared with CuATSM, as proved by uptake, internalization and externalization studies that were performed using the radioactive congeners 64CuL1-64CuL4. The enhanced cellular uptake of CuL1-CuL4 indicates that this new family of CuIIBTSC complexes deserves to be further evaluated in the design of metallodrugs for cancer theranostics.

Authors: E. Palma, F. Mendes, G. R. Morais, I. Rodrigues, I. C. Santos, M. P. Campello, P. Raposinho, I. Correia, S. Gama, D. Belo, V. Alves, A. J. Abrunhosa, I. Santos, A. Paulo

Date Published: 3rd Dec 2016

Publication Type: Not specified

Catechol, a major component of smoke, influences primary root growth and root hair elongation through reactive oxygen species-mediated redox signaling

Abstract (Expand)

Nicotiana attenuata germinates from long-lived seedbanks in native soils after fires. Although smoke signals have been known to break seed dormancy, whether they also affect seedling establishment and … root development remains unclear. In order to test this, seedlings were treated with smoke solutions. Seedlings responded in a dose-dependent manner with significantly increased primary root lengths, due mainly to longitudinal cell elongation, increased numbers of lateral roots and impaired root hair development. Bioassay-driven fractionations and NMR were used to identify catechol as the main active compound for the smoke-induced root phenotype. The transcriptome analysis revealed that mainly genes related to auxin biosynthesis and redox homeostasis were altered after catechol treatment. However, histochemical analyses of reactive oxygen species (ROS) and the inability of auxin applications to rescue the phenotype clearly indicated that highly localized changes in the root's redox-status, rather than in levels of auxin, are the primary effector. Moreover, H2 O2 application rescued the phenotype in a dose-dependent manner. Chemical cues in smoke not only initiate seed germination, but also influence seedling root growth; understanding how these cues work provides new insights into the molecular mechanisms by which plants adapt to post-fire environments.

Authors: M. Wang, M. Schoettner, S. Xu, C. Paetz, J. Wilde, I. T. Baldwin, K. Groten

Date Published: 24th Nov 2016

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

Plant-like biosynthesis of isoquinoline alkaloids in Aspergillus fumigatus

Abstract (Expand)

Natural product discovery efforts have focused primarily on microbial biosynthetic gene clusters (BGCs) containing large multimodular polyketide synthases and nonribosomal peptide synthetases; however, … sequencing of fungal genomes has revealed a vast number of BGCs containing smaller NRPS-like genes of unknown biosynthetic function. Using comparative metabolomics, we show that a BGC in the human pathogen Aspergillus fumigatus named fsq, which contains an NRPS-like gene lacking a condensation domain, produces several new isoquinoline alkaloids known as the fumisoquins. These compounds derive from carbon-carbon bond formation between two amino acid-derived moieties followed by a sequence that is directly analogous to isoquinoline alkaloid biosynthesis in plants. Fumisoquin biosynthesis requires the N-methyltransferase FsqC and the FAD-dependent oxidase FsqB, which represent functional analogs of coclaurine N-methyltransferase and berberine bridge enzyme in plants. Our results show that BGCs containing incomplete NRPS modules may reveal new biosynthetic paradigms and suggest that plant-like isoquinoline biosynthesis occurs in diverse fungi.

Authors: J. A. Baccile, J. E. Spraker, H. H. Le, E. Brandenburger, C. Gomez, J. W. Bok, J. Macheleidt, A. A. Brakhage, D. Hoffmeister, N. P. Keller, F. C. Schroeder

Date Published: 12th Apr 2016

Publication Type: Not specified

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

Plant pathogenic anaerobic bacteria use aromatic polyketides to access aerobic territory

Abstract (Expand)

Around 25% of vegetable food is lost worldwide because of infectious plant diseases, including microbe-induced decay of harvested crops. In wet seasons and under humid storage conditions, potato tubers … are readily infected and decomposed by anaerobic bacteria (Clostridium puniceum). We found that these anaerobic plant pathogens harbor a gene locus (type II polyketide synthase) to produce unusual polyketide metabolites (clostrubins) with dual functions. The clostrubins, which act as antibiotics against other microbial plant pathogens, enable the anaerobic bacteria to survive an oxygen-rich plant environment.

Authors: G. Shabuer, K. Ishida, S. J. Pidot, M. Roth, H. M. Dahse,

Date Published: 7th Nov 2015

Publication Type: Not specified

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

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