14 results on '"Scott, Barry"'
Search Results
2. Disruption of Signaling in a Fungal-Grass Symbiosis Leads to Pathogenesis
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Eaton, Carla J., Cox, Murray P., Ambrose, Barbara, Becker, Matthias, Hesse, Uljana, Schardl, Christopher L., and Scott, Barry
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- 2010
3. Molecular Cloning and Functional Analysis of Gene Clusters for the Biosynthesis of Indole-Diterpenes in Penicillium crustosum and P. janthinellum.
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Nicholson, Matthew J., Eaton, Carla J., Stärkel, Cornelia, Tapper, Brian A., Cox, Murray P., and Scott, Barry
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MOLECULAR cloning ,BIOSYNTHESIS ,DITERPENES ,PENICILLIUM ,POLYMERASE chain reaction ,ASPERGILLUS - Abstract
The penitremane and janthitremane families of indole-diterpenes are abundant natural products synthesized by Penicillium crustosum and P. janthinellum. Using a combination of PCR, cosmid library screening, and Illumina sequencing we have identified gene clusters encoding enzymes for the synthesis of these compounds. Targeted deletion of penP in P. crustosum abolished the synthesis of penitrems A, B, D, E, and F, and led to accumulation of paspaline, a key intermediate for paxilline biosynthesis in P. paxilli. Similarly, deletion of janP and janD in P. janthinellum abolished the synthesis of prenyl-elaborated indole-diterpenes, and led to accumulation in the latter of 13-desoxypaxilline, a key intermediate for the synthesis of the structurally related aflatremanes synthesized by Aspergillus flavus. This study helps resolve the genetic basis for the complexity of indole-diterpene natural products found within the Penicillium and Aspergillus species. All indole-diterpene gene clusters identified to date have a core set of genes for the synthesis of paspaline and a suite of genes encoding multi-functional cytochrome P450 monooxygenases, FAD dependent monooxygenases, and prenyl transferases that catalyse various regio- and stereo- specific oxidations that give rise to the diversity of indole-diterpene products synthesized by this group of fungi. [ABSTRACT FROM AUTHOR]
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- 2015
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4. Four gene products are required for the fungal synthesis of the indole-diterpene, paspaline
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Saikia, Sanjay, Parker, Emily J., Koulman, Albert, and Scott, Barry
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DITERPENES ,BIOSYNTHESIS ,GENES ,BIOLOGICAL transport - Abstract
Abstract: Paspaline belongs to a large, structurally and functionally diverse group of indole-diterpenes synthesized by filamentous fungi. However, the identity of the gene products required for the biosynthesis of paspaline, a key intermediate for the synthesis of paxilline and other indole-diterpenes, is not known. Transfer of constructs containing different pax gene combinations into a paxilline negative deletion derivative of Penicillium paxilli demonstrated that just four proteins, PaxG, a geranylgeranyl diphosphate synthase, PaxM, a FAD-dependent monooxygenase, PaxB, a putative membrane protein, and PaxC, a prenyl transferase, are required for the biosynthesis of paspaline. [Copyright &y& Elsevier]
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- 2006
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5. Minimum Information about a Biosynthetic Gene cluster
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Medema, Marnix H, Kottmann, Renzo, Yilmaz, Pelin, Cummings, Matthew, Biggins, John B, Blin, Kai, de Bruijn, Irene, Chooi, Yit Heng, Claesen, Jan, Coates, R Cameron, Cruz-Morales, Pablo, Duddela, Srikanth, Düsterhus, Stephanie, Edwards, Daniel J, Fewer, David P, Garg, Neha, Geiger, Christoph, Gomez-Escribano, Juan Pablo, Greule, Anja, Hadjithomas, Michalis, Haines, Anthony S, Helfrich, Eric J N, Hillwig, Matthew L, Ishida, Keishi, Jones, Adam C, Jones, Carla S, Jungmann, Katrin, Kegler, Carsten, Kim, Hyun Uk, Kötter, Peter, Krug, Daniel, Masschelein, Joleen, Melnik, Alexey V, Mantovani, Simone M, Monroe, Emily A, Moore, Marcus, Moss, Nathan, Nützmann, Hans-Wilhelm, Pan, Guohui, Pati, Amrita, Petras, Daniel, Reen, F Jerry, Rosconi, Federico, Rui, Zhe, Tian, Zhenhua, Tobias, Nicholas J, Tsunematsu, Yuta, Wiemann, Philipp, Wyckoff, Elizabeth, Yan, Xiaohui, Yim, Grace, Yu, Fengan, Xie, Yunchang, Aigle, Bertrand, Apel, Alexander K, Balibar, Carl J, Balskus, Emily Patricia, Barona-Gómez, Francisco, Bechthold, Andreas, Bode, Helge B, Borriss, Rainer, Brady, Sean F, Brakhage, Axel A, Caffrey, Patrick, Cheng, Yi-Qiang, Clardy, Jon C., Cox, Russell J, De Mot, René, Donadio, Stefano, Donia, Mohamed S, van der Donk, Wilfred A, Dorrestein, Pieter C, Doyle, Sean, Driessen, Arnold J M, Ehling-Schulz, Monika, Entian, Karl-Dieter, Fischbach, Michael A, Gerwick, Lena, Gerwick, William H, Gross, Harald, Gust, Bertolt, Hertweck, Christian, Höfte, Monica, Jensen, Susan E, Ju, Jianhua, Katz, Leonard, Kaysser, Leonard, Klassen, Jonathan L, Keller, Nancy P, Kormanec, Jan, Kuipers, Oscar P, Kuzuyama, Tomohisa, Kyrpides, Nikos C, Kwon, Hyung-Jin, Lautru, Sylvie, Lavigne, Rob, Lee, Chia Y, Linquan, Bai, Liu, Xinyu, Liu, Wen, Luzhetskyy, Andriy, Mahmud, Taifo, Mast, Yvonne, Méndez, Carmen, Metsä-Ketelä, Mikko, Micklefield, Jason, Mitchell, Douglas A, Moore, Bradley S, Moreira, Leonilde M, Müller, Rolf, Neilan, Brett A, Nett, Markus, Nielsen, Jens, O, Fergal, Oikawa, Hideaki, Osbourn, Anne, Osburne, Marcia S, Ostash, Bohdan, Payne, Shelley M, Pernodet, Jean-Luc, Petricek, Miroslav, Piel, Jörn, Ploux, Olivier, Raaijmakers, Jos M, Salas, José A, Schmitt, Esther K, Scott, Barry, Seipke, Ryan F, Shen, Ben, Sherman, David, Sivonen, Kaarina, Smanski, Michael J, Sosio, Margherita, Stegmann, Evi, Süssmuth, Roderich D, Tahlan, Kapil, Thomas, Christopher M, Tang, Yi, Truman, Andrew W, Viaud, Muriel, Walton, Jonathan D, Walsh, Christopher T., Weber, Tilmann, van Wezel, Gilles P, Wilkinson, Barrie, Willey, Joanne M, Wohlleben, Wolfgang, Wright, Gerard D, Ziemert, Nadine, Zhang, Changsheng, Zotchev, Sergey B, Breitling, Rainer, Takano, Eriko, and Glöckner, Frank Oliver
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Biosynthesis ,Natural products ,Sequence annotation ,Synthetic biology - Abstract
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard., Chemistry and Chemical Biology
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- 2015
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6. What triggers grass endophytes to switch from mutualism to pathogenism?
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Eaton, Carla J., Cox, Murray P., and Scott, Barry
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ENDOPHYTES , *BIOSYNTHESIS , *SYMBIOSIS , *REACTIVE oxygen species , *CLAVICIPITACEAE , *GRASSES , *GENE expression in plants , *MITOGEN-activated protein kinases - Abstract
Abstract: Symbioses between cool season grasses and fungi of the family Clavicipitaceae are an integral component of both natural and agricultural ecosystems. An excellent experimental model is the association between the biotrophic fungus Epichloë festucae and Lolium perenne (perennial ryegrass). The fungal partner produces a suite of secondary metabolites that protect the host from various biotic and abiotic stresses. The plant host provides a source of nutrients and a mechanism of dissemination via seed transmission. Crucial mechanisms that maintain a stable mutualistic association include signaling through the stress activated MAP kinase pathway and production of reactive oxygen species by the fungal NADPH oxidase (Nox) complex. Disruption of components of the Nox complex (NoxA, NoxR and RacA), or the stress-activated MAP kinase (SakA), leads to a breakdown in this finely balanced association, resulting in pathogenic infection instead of mutualism. Hosts infected with fungi lacking a functional Nox complex, or the stress-activated MAP kinase, display a stunted phenotype and undergo premature senescence, while the fungus switches from restricted to proliferative growth. To gain insight into the mechanisms that underlie these physiological changes, high throughput mRNA sequencing has been used to analyze the transcriptomes of both host and symbiont in wild-type and a mutant association. In the ΔsakA mutant association, a dramatic up-regulation of fungal hydrolases and transporters was observed, changes consistent with a switch from restricted symbiotic to proliferative pathogenic growth. Analysis of the plant transcriptome revealed dramatic changes in expression of host genes involved in pathogen defense, transposon activation and hormone biosynthesis and response. This review highlights how finely tuned grass-endophyte associations are, and how interfering with the signaling pathways involved in maintenance of these associations can trigger a change from mutualistic to pathogenic interaction. [Copyright &y& Elsevier]
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- 2011
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7. Complex epigenetic regulation of alkaloid biosynthesis and host interaction by heterochromatin protein I in a fungal endophyte-plant symbiosis.
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Chujo, Tetsuya, Lukito, Yonathan, Eaton, Carla J., Dupont, Pierre-Yves, Johnson, Linda J., Winter, David, Cox, Murray P., and Scott, Barry
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DITERPENES , *BIOSYNTHESIS , *FUNGAL proteins , *GENE expression - Abstract
Highlights • The E. festucae heterochromatin protein I regulates subtelomeric eas and ltm gene expression. • Deletion of hepA leads to derepression of eas and ltm genes in axenic culture. • HepA fails to localize to the nucleus in the Δ hepA mutant. • Just one third of genes differentially expressed in hepA in culture are upregulated. • Deletion of hepA has a dramatic effect on the plant host interaction phenotype. • Two thirds of genes differentially expressed in hepA in planta are upregulated. Abstract Epichloë festucae forms mutualistic symbiotic interactions with grasses of the Lolium and Festuca genera. Protection from insect and mammalian herbivory are the best-documented host benefits of these associations. The two main classes of anti-mammalian alkaloids synthesized by E. festucae are the ergot alkaloids and indole diterpenes, of which ergovaline and lolitrems are the principal terminal products. Synthesis of both metabolites require multiple gene products encoded by clusters of 11 genes located at the subtelomeric regions of chromosomes I and III respectively. These loci are essentially unexpressed in axenic culture but among the most highly expressed genes in planta. We show here that heterochromatin 1 protein (HepA) is an important component of the regulatory machinery that maintains these loci in a silent state in culture. Deletion of this gene led to derepression of eas and ltm gene expression under non-symbiotic culture conditions. Although there was no obvious culture phenotype, RNAseq analysis revealed that around 1000 genes were differentially expressed in the Δ hepA mutant compared to wild type with just one-third upregulated. Inoculation of the Δ hepA mutants into seedlings of Lolium perenne led to a severe host interaction phenotype characterized by a reduction in tiller length but an increase in tiller number. Hyphae within the leaves of these associations were much more abundant in the intercellular spaces of the leaves and aberrantly colonized the vascular bundles. This physiological change was accompanied by a dramatic change in the transcriptome with around 900 genes differentially expressed, with two thirds of these upregulated. This major physiological change was accompanied by a decrease in ltm gene expression and loss of the ability to synthesize lolitrems. These results show that HepA has an important role in controlling the chromatin state of these sub-telomeric secondary metabolite genes, including their symbiosis-specific regulation. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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8. Heterologous Biosynthesis of Nodulisporic Acid F.
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Van de Bittner, Kyle C., Nicholson, Matthew J., Bustamante, Leyla Y., Parker, Emily J., Kessans, Sarah A., Ram, Arvina, Scott, Barry, and van Dolleweerd, Craig J.
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DITERPENES , *INDOLE , *GENES , *GENE clusters , *BIOSYNTHESIS , *ENZYMES , *EPOXIDASES , *CARBOXYLIC acids - Abstract
Nodulisporic acids comprise a group of valuable indole diterpenes that exhibit potent insecticidal activities. We report the identification of a gene cluster in the genome of the filamentous fungus Hypoxylon pulicicidum (Nodulisporium sp.) that contains genes responsible for the biosynthesis of nodulisporic acids. Using Pénicillium paxilli as a heterologous host, and through pathway reconstitution experiments, we identified the function of four genes involved in the biosynthesis of the nodulisporic acid core compound, nodulisporic acid F (NAF). Two of these genes (nodM and nodW) are especially significant as they encode enzymes with previously unreported functionality: nodM encodes a 3-geranylgeranylindole epoxidase capable of catalyzing only a single epoxidation step to prime formation of the distinctive ring structure of nodulisporic acids, and nodW encodes the first reported gene product capable of introducing a carboxylic acid moiety to an indole diterpene core structure that acts as a reactive handle for further modification. Here, we present the enzymatic basis for the biosynthetic branch point that gives rise to nodulisporic acids. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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9. Biosynthesis of Shearinine: Diversification of a Tandem Prenyl Moiety of Fungal Indole Diterpenes.
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Chengwei Liu, Atsushi Minami, Tohru Dairi, Katsuya Gomi, Scott, Barry, and Hideaki Oikawa
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INDOLE compounds , *BIOSYNTHESIS , *KOJI , *DITERPENES , *OXIDASES - Abstract
The late-stage biosynthetic pathway of the indole diterpene shearinine involving four enzymatic reactions (JanQDOJ) was elucidated by an efficient heterologous expression system using Aspergillus oryzae. Key oxidative cyclization, forming a characteristic A/B bicyclic shearinine core by flavoprotein oxidase, was studied using a substrate analogue and a buffer containing H218O. These experimental data provided evidence that JanO catalyzes two-step oxidation via a hydroxylated product and that the JanO reaction involves the hydride-transfer mechanism. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Identification of Two Aflatrem Biosynthesis Gene Loci in Aspergillus flavus and Metabolic Engineering of Penicillium paxilli To Elucidate Their Function.
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Nicholson, Matthew J., Koulman, Albert, Monahan, Brendon J., Pritchard, Beth L., Payne, Gary A., and Scott, Barry
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ASPERGILLUS flavus , *BIOSYNTHESIS , *PENICILLIUM , *FILAMENTOUS fungi , *METABOLITES , *DITERPENES , *REVERSE transcriptase polymerase chain reaction , *GENETIC transcription , *NUCLEOTIDE sequence , *PHYSIOLOGY - Abstract
Aflatrem is a potent tremorgenic toxin produced by the soil fungus Aspergillus flavus, and a member of a structurally diverse group of fungal secondary metabolites known as indole-diterpenes. Gene clusters for indole-diterpene biosynthesis have recently been described in several species of filamentous fungi. A search of Aspergillus complete genome sequence data identified putative aflatrem gene clusters in the genomes of A. flavus and Aspergillus oryzae. In both species the genes for aflatrem biosynthesis cluster at two discrete loci; the first, ATM1, is telomere proximal on chromosome 5 and contains a cluster of three genes, atmG, atmC, and atmM, and the second, ATM2, is telomere distal on chromosome 7 and contains five genes, atmD, atmQ, atmB, atmA, and atmP. Reverse transcriptase PCR in A. flavus demonstrated that aflatrem biosynthesis transcript levels increased with the onset of aflatrem production. Transfer of atmP and atmQ into Penicillium paxilli paxP and paxQ deletion mutants, known to accumulate paxilline intermediates paspaline and 13-desoxypaxilline, respectively, showed that AtmP is a functional homolog of PaxP and that AtmQ utilizes 13-desoxypaxilline as a substrate to synthesize aflatrem pathway-specific intermediates, paspalicine and paspalinine. We propose a scheme for aflatrem biosynthesis in A. flavus based on these reconstitution experiments in P. paxilli and identification of putative intermediates in wild-type cultures of A. flavus. [ABSTRACT FROM AUTHOR]
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- 2009
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11. Indole-Diterpene Biosynthetic Capability of Epichloë Endophytes as Predicted by ltm Gene Analysis.
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Young, Carolyn A., Tapper, Brian A., May, Kimberley, Moon, Christina D., Schardl, Christopher L., and Scott, Barry
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NEOTYPHODIUM , *EPICHLOE , *ALKALOIDS , *ENDOPHYTES , *ENDOPHYTIC fungi , *BIOSYNTHESIS , *MICROBIAL ecology , *BACTERIAL ecology , *MICROBIOLOGY - Abstract
Bioprotective alkaloids produced by Epichloë and closely related asexual Neotyphodium fungal endophytes protect their grass hosts from insect and mammalian herbivory. One class of these compounds, known for antimammalian toxicity, is the indolediterpenes. The LTM locus of Neolyphodium Iolii (Lp19) and Epichloë festuce (FI1), required for the biosynthesis of the indole-diterpene lolitrem, consists of 10 ltm genes. We have used PCR and Southern analysis to screen a broad taxonomic range of 44 endophyte isolates to determine why indole-diterpenes are present in so few endophyte-grass associations in comparison to that of the other bioprotective alkaloids, which are more widespread among the endophtyes. All 10 ltm genes were present in only three epichloe endophytes. A predominance of the asexual Neotyphodium spp. examined contained 8 of the 10 ltm genes, with only one N. Iolii containing the entire LTM locus and the ability to produce lolitrems. Liquid chromatography-tandem mass spectrometry profiles of indole-diterpenes from a subset of endophyte-infected perennial ryegrass showed that endophytes that contained functional genes present in ltm clusters 1 and 2 were capable of producing simple indole-diterpenes such as paspaline, 13-desoxypaxilline, and terpendoles, compounds predicted to be precursors of lolitrem B. Analysis of toxin biosynthesis genes by PCR now enables a diagnostic method to screen endophytes for both beneficial and detrimental alkaloids and can be used as a resource for screening isolates required for forage improvement. [ABSTRACT FROM AUTHOR]
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- 2009
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12. The genetic basis for indole-diterpene chemical diversity in filamentous fungi
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Saikia, Sanjay, Nicholson, Matthew J., Young, Carolyn, Parker, Emily J., and Scott, Barry
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FILAMENTOUS fungi , *FUNGAL development , *INDOLE , *INSECT-plant relationships , *PARASITIC plants , *BIOSYNTHESIS - Abstract
Abstract: Indole-diterpenes are a structurally diverse group of secondary metabolites with a common cyclic diterpene backbone derived from geranylgeranyl diphosphate and an indole group derived from indole-3-glycerol phosphate. Different types and patterns of ring substitutions and ring stereochemistry generate this structural diversity. This group of compounds is best known for their neurotoxic effects in mammals, causing syndromes such as ‘ryegrass staggers’ in sheep and cattle. Because many of the fungi that synthesise these compounds form symbiotic relationships with plants, insects, and other fungi, the synthesis of these compounds may confer an ecological advantage to these associations. Considerable recent progress has been made on understanding indole-diterpene biosynthesis in filamentous fungi, principally through the cloning and characterisation of the genes and gene products for paxilline biosynthesis in Penicillium paxilli. Important insights into how the indole-diterpene backbone is synthesised and decorated have been obtained using P. paxilli mutants in this pathway. This review provides an overview of these recent developments. [Copyright &y& Elsevier]
- Published
- 2008
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13. Defininci Paxilline Biosynthesis in Penicillium paxilli.
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Saikia, Sanjay, Parker, Emily J., Koulman, Albert, and Scott, Barry
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BIOSYNTHESIS , *PENICILLIUM , *DITERPENES , *METABOLITES , *BIOCHEMISTRY - Abstract
Indole diterpenes are a large, structurally and functionally diverse group of secondary metabolites produced by filamentous fungi. Biosynthetic schemes have been proposed for these metabolites but until recently none of the proposed steps had been validated by biochemical or genetic studies. Using Penicillium paxilli as a model experimental system to study indole diterpene biosynthesis we previously showed by deletion analysis that a cluster of seven genes is required for paxilline biosynthesis. Two of these pax genes, paxP and paxQ (encoding cytochrome P450 monooxygenases), are required in the later steps in this pathway. Here, we describe the function of paxP and paxQ gene products by feeding proposed paxilline intermediates to strains lacking the pax cluster but containing ectopically integrated copies of paxP or paxQ. Transformants containing paxP converted paspaline into β-desoxypaxilline as the major product and β-PC-M6 as the minor product. β-PC-M6, but not α-PC-M6, was also a substrate for PaxP and was converted to 13-desoxypaxilline. paxQ-containing transformants converted 13-desoxypaxilline into paxilline. These results confirm that paspaline, β-PC-M6, and 13-desoxypaxilline are paxilline intermediates and that paspaline and β-PC-M6 are substrates for PaxP, and 13-desoxypaxilline is a substrate for PaxQ. PaxP and PaxQ also utilized β-paxitriol and α-PC-M6 as substrates converting them to paxilline and a-paxitriol, respectively. These findings have allowed us to delineate clearly the biosynthetic pathway for paxilline for the first time. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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14. A complex gene cluster for indole-diterpene biosynthesis in the grass endophyte Neotyphodium lolii
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Young, Carolyn A., Felitti, Silvina, Shields, Katherine, Spangenberg, German, Johnson, Richard D., Bryan, Gregory T., Saikia, Sanjay, and Scott, Barry
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BIOSYNTHESIS , *NEOTYPHODIUM , *MYCOTOXINS , *NUCLEIC acid hybridization - Abstract
Abstract: Lolitrems are a structurally diverse group of indole-diterpene mycotoxins synthesized by Epichloë/Neotyphodium endophytes in association with Pooid grasses. Using suppression subtractive hybridization combined with chromosome walking, two clusters of genes for lolitrem biosynthesis were isolated from Neotyphodium lolii, a mutualistic endophyte of perennial ryegrass. The first cluster contains five genes, ltmP, ltmQ, ltmF, ltmC, and ltmB, four of which appear to be orthologues of functionally characterized genes from Penicillium paxilli. The second cluster contains two genes, ltmE and ltmJ, that appear to be unique to lolitrem biosynthesis. The two clusters are separated by a 16kb AT-rich sequence that includes two imperfect direct repeats. A previously isolated ltm cluster composed of ltmG, ltmM, and ltmK, is linked to these two new clusters by 35kb of AT-rich retrotransposon relic sequence. All 10 genes at this complex LTM locus were highly expressed in planta but expression was very low or undetectable in mycelia. ltmM and ltmC were shown to be functional orthologues of P. paxilli paxM and paxC, respectively. This work provides a genetic foundation for elucidating the metabolic grid responsible for the diversity of indole-diterpenes synthesized by N. lolii. [Copyright &y& Elsevier]
- Published
- 2006
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