Secondary Metabolite

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Clay C C Wang - One of the best experts on this subject based on the ideXlab platform.

  • heterologous expression of fungal Secondary Metabolite pathways in the aspergillus nidulans host system
    Methods in Enzymology, 2016
    Co-Authors: J W A Van Dijk, Clay C C Wang
    Abstract:

    Heterologous expression of fungal Secondary Metabolite genes allows for the product formation of otherwise silent Secondary Metabolite biosynthesis pathways. It also allows facile expression of mutants or combinations of genes not found in nature. This capability makes model fungi an ideal platform for synthetic biology. In this chapter a detailed description is provided of how to heterologously express any fungal Secondary Metabolite gene(s) in a well-developed host strain of Aspergillus nidulans. It covers all the necessary steps from identifying a gene(s) of interest to culturing mutant strains to produce Secondary Metabolites.

  • an efficient system for heterologous expression of Secondary Metabolite genes in aspergillus nidulans
    Journal of the American Chemical Society, 2013
    Co-Authors: Yiming Chiang, Clay C C Wang, Elizabeth C Oakley, Manmeet Ahuja, Ruth Entwistle, Aric Schultz, Shulin Chang, Calvin T Sung, Berl R Oakley
    Abstract:

    Fungal Secondary Metabolites (SMs) are an important source of medically valuable compounds. Genome projects have revealed that fungi have many SM biosynthetic gene clusters that are not normally expressed. To access these potentially valuable, cryptic clusters, we have developed a heterologous expression system in Aspergillus nidulans. We have developed an efficient system for amplifying genes from a target fungus, placing them under control of a regulatable promoter, transferring them into A. nidulans, and expressing them. We have validated this system by expressing nonreducing polyketide synthases of Aspergillus terreus and additional genes required for compound production and release. We have obtained compound production and release from six of these nonreducing polyketide synthases and have identified the products. To demonstrate that the procedure allows transfer and expression of entire Secondary Metabolite biosynthetic pathways, we have expressed all the genes of a silent A. terreus cluster and dem...

  • advances in aspergillus Secondary Metabolite research in the post genomic era
    Natural Product Reports, 2012
    Co-Authors: James F Sanchez, Amber D Somoza, Nancy P Keller, Clay C C Wang
    Abstract:

    This review studies the impact of whole genome sequencing on Aspergillus Secondary Metabolite research. There has been a proliferation of many new, intriguing discoveries since sequencing data became widely available. What is more, the genomes disclosed the surprising finding that there are many more Secondary Metabolite biosynthetic pathways than laboratory research had suggested. Activating these pathways has been met with some success, but many more dormant genes remain to be awakened.

Toyoki Kozai - One of the best experts on this subject based on the ideXlab platform.

  • temperature stress can alter the photosynthetic efficiency and Secondary Metabolite concentrations in st john s wort
    Plant Physiology and Biochemistry, 2005
    Co-Authors: S. M. A. Zobayed, F. Afreen, Toyoki Kozai
    Abstract:

    Temperature stress is known to cause many physiological, biochemical and molecular changes in plant metabolism and possibly alter the Secondary Metabolite production in plants. The hypothesis of the current study was that temperature stress can increase the Secondary Metabolite concentrations in St. John's wort. Plants were grown under controlled environments with artificial light using cool white fluorescent lamps and CO2 enrichment and 70-day-old plants were subjected for 15 days to different temperature treatments of 15, 20, 25, 30 and 35 degrees C before harvested. Major aim of the study was to increase the major Secondary Metabolites in St. John's wort by applying temperature stress and to evaluate the physiological status of the plant especially the photosynthetic efficiency and peroxidase activity of the leaf tissues exposed to different temperatures under precisely controlled environmental factors. Results revealed that relatively high (35 degrees C) or low (15 degrees C) temperatures reduced the photosynthetic efficiency of the leaves of St. John's wort plants and resulted in low CO2 assimilation. Net photosynthetic rates and the maximal quantum efficiency of PSII photochemistry of the dark adopted leaves (phi(p)max) decreased significantly in the leaves of plants grown under 35 or 15 degrees C temperature treatments. High temperature (35 degrees C) treatment increased the leaf total peroxidase activity and also increased the hypericin, pseudohypericin and hyperforin concentrations in the shoot tissues. These results provide the first indication that temperature is an important environmental factor to optimize the Secondary Metabolite production in St. John's wort and controlled environment technology can allow the precise application of such specific stresses.

  • temperature stress can alter the photosynthetic efficiency and Secondary Metabolite concentrations in st john s wort
    Plant Physiology and Biochemistry, 2005
    Co-Authors: S. M. A. Zobayed, F. Afreen, Toyoki Kozai
    Abstract:

    Abstract Temperature stress is known to cause many physiological, biochemical and molecular changes in plant metabolism and possibly alter the Secondary Metabolite production in plants. The hypothesis of the current study was that temperature stress can increase the Secondary Metabolite concentrations in St. John's wort. Plants were grown under controlled environments with artificial light using cool white fluorescent lamps and CO 2 enrichment and 70-day-old plants were subjected for 15 days to different temperature treatments of 15, 20, 25, 30 and 35 °C before harvested. Major aim of the study was to increase the major Secondary Metabolites in St. John's wort by applying temperature stress and to evaluate the physiological status of the plant especially the photosynthetic efficiency and peroxidase activity of the leaf tissues exposed to different temperatures under precisely controlled environmental factors. Results revealed that relatively high (35 °C) or low (15 °C) temperatures reduced the photosynthetic efficiency of the leaves of St. John's wort plants and resulted in low CO 2 assimilation. Net photosynthetic rates and the maximal quantum efficiency of PSII photochemistry of the dark adopted leaves (ϕ p max ) decreased significantly in the leaves of plants grown under 35 or 15 °C temperature treatments. High temperature (35 °C) treatment increased the leaf total peroxidase activity and also increased the hypericin, pseudohypericin and hyperforin concentrations in the shoot tissues. These results provide the first indication that temperature is an important environmental factor to optimize the Secondary Metabolite production in St. John's wort and controlled environment technology can allow the precise application of such specific stresses.

  • Relationships between net photosynthetic rate and Secondary Metabolite contents in St. John's wort
    Plant Science, 2005
    Co-Authors: Kriengkrai Mosaleeyanon, S. M. A. Zobayed, F. Afreen, Toyoki Kozai
    Abstract:

    Abstract Hypericum perforatum L. (St. John's wort), a traditional herb with antidepressive and wound healing properties, was grown under 100, 300 and 600 μmol m −2  s −1 photosynthetic photon flux (PPF) each with 500, 1000 and 1500 μmol mol −1 CO 2 , with the objective of maximizing the biomass and Secondary Metabolite production. Plants grown in the field (1770 μmol m −2  s −1 PPF and 380 μmol mol −1 CO 2 ) were used as a control. On day 45, total fresh and dry mass, and the number of stem nodes were greatest in plants grown under 600 μmol m −2  s −1 PPF with 1500 μmol mol −1 CO 2 concentration (HH-treatment) and were 29, 30 and 4 times greater, respectively, than those of the control. Leaf net photosynthetic rate (Pn) increased with increasing PPF and/or CO 2 concentration, with the highest value occurring in the plants grown under the HH-treatment. Secondary Metabolite contents (mg/plant) in the leaf tissues were generally higher in the plants grown under the controlled environments than those in the field (control). Hypericin and pseudohypericin contents were highest in the HH-treatment, being 30 and 41 times greater, respectively, than those of the control. Hypericin and pseudohypericin contents in the leaf tissues increased with increasing Pn. The second order polynomial correlations between Pn and hypericin, and between Pn and pseudohypericin contents with R 2 of 0.82 and 0.79, respectively, were obtained. Moreover, total hypericin (hypericin + pseudohypericin) concentration (mg g −1 leaf DM) in leaf tissues was related to both PPF and CO 2 concentration as expressed by second order polynomial correlations ( R 2  = 1). Therefore, growing St. John's wort plants under a controlled environment can enhance biomass and Secondary Metabolite production by increasing net photosynthetic rate.

Nancy P Keller - One of the best experts on this subject based on the ideXlab platform.

  • advances in aspergillus Secondary Metabolite research in the post genomic era
    Natural Product Reports, 2012
    Co-Authors: James F Sanchez, Amber D Somoza, Nancy P Keller, Clay C C Wang
    Abstract:

    This review studies the impact of whole genome sequencing on Aspergillus Secondary Metabolite research. There has been a proliferation of many new, intriguing discoveries since sequencing data became widely available. What is more, the genomes disclosed the surprising finding that there are many more Secondary Metabolite biosynthetic pathways than laboratory research had suggested. Activating these pathways has been met with some success, but many more dormant genes remain to be awakened.

  • hdaa a class 2 histone deacetylase of aspergillus fumigatus affects germination and Secondary Metabolite production
    Fungal Genetics and Biology, 2009
    Co-Authors: Inhyung Lee, Keats E Shwab, Taylor R T Dagenais, David R Andes, Nancy P Keller
    Abstract:

    Histone deacetylases (HDACs) play an important role in regulation of gene expression through histone modifications. Here we show that the Aspergillus fumigatus HDAC HdaA is involved in regulation of Secondary Metabolite production and is required for normal germination and vegetative growth. Deletion of the hdaA gene increased the production of several Secondary Metabolites but decreased production of gliotoxin whereas over-expression hdaA increased production of gliotoxin. RT-PCR analysis of 14 nonribosomal peptide synthases indicated HdaA regulation of up to nine of them. A mammalian cell toxicity assay indicated increased activity in the over-expression strain. Neither mutant affected virulence of the fungus as measured by macrophage engulfment of conidia or virulence in a neutropenic mouse model.

  • regulation of Secondary Metabolite production in filamentous ascomycetes
    Fungal Biology, 2008
    Co-Authors: Keats E Shwab, Nancy P Keller
    Abstract:

    Fungi are renowned for their ability to produce bioactive small molecules otherwise known as Secondary Metabolites. These molecules have attracted much attention due to both detrimental (e.g. toxins) and beneficial (e.g. pharmaceuticals) effects on human endeavors. Once the topic only of chemical and biochemical studies, Secondary metabolism research has reached a sophisticated level in the realm of genetic regulation. This review covers the latest insights into the processes regulating Secondary Metabolite production in filamentous fungi.

  • paradigm shifts in fungal Secondary Metabolite research
    Fungal Biology, 2008
    Co-Authors: Marc Stadler, Nancy P Keller
    Abstract:

    The 8th International Mycological Congress (IMC8; Cairns, Australia) hosted several plenary lectures, poster presentations, and even entire symposia dedicated to fungal Secondary Metabolites (extrolites). These advances, presented in this special issue, together demonstrated how the impact of molecular biology and genomics and the availability of sophisticated methods of analytical chemistry has resulted in paradigm shifts in our understanding of fungal Secondary metabolism and its key role in fungal biology. Rather than focus on classical topics such as discovery of novel drug candidates and identification of toxins, here we address two major themes in this special issue: (1) the utility and importance of Secondary Metabolites and their genes in polyphasic taxonomy, phylogeny, and evolutionary history of kingdom Fungi (syn. Eumycota); and (2) the genetic processes regulating Secondary Metabolite biosynthesis. The history of fungal chemotaxonomy and some important classes of Secondary Metabolites are reviewed.

S. M. A. Zobayed - One of the best experts on this subject based on the ideXlab platform.

  • temperature stress can alter the photosynthetic efficiency and Secondary Metabolite concentrations in st john s wort
    Plant Physiology and Biochemistry, 2005
    Co-Authors: S. M. A. Zobayed, F. Afreen, Toyoki Kozai
    Abstract:

    Temperature stress is known to cause many physiological, biochemical and molecular changes in plant metabolism and possibly alter the Secondary Metabolite production in plants. The hypothesis of the current study was that temperature stress can increase the Secondary Metabolite concentrations in St. John's wort. Plants were grown under controlled environments with artificial light using cool white fluorescent lamps and CO2 enrichment and 70-day-old plants were subjected for 15 days to different temperature treatments of 15, 20, 25, 30 and 35 degrees C before harvested. Major aim of the study was to increase the major Secondary Metabolites in St. John's wort by applying temperature stress and to evaluate the physiological status of the plant especially the photosynthetic efficiency and peroxidase activity of the leaf tissues exposed to different temperatures under precisely controlled environmental factors. Results revealed that relatively high (35 degrees C) or low (15 degrees C) temperatures reduced the photosynthetic efficiency of the leaves of St. John's wort plants and resulted in low CO2 assimilation. Net photosynthetic rates and the maximal quantum efficiency of PSII photochemistry of the dark adopted leaves (phi(p)max) decreased significantly in the leaves of plants grown under 35 or 15 degrees C temperature treatments. High temperature (35 degrees C) treatment increased the leaf total peroxidase activity and also increased the hypericin, pseudohypericin and hyperforin concentrations in the shoot tissues. These results provide the first indication that temperature is an important environmental factor to optimize the Secondary Metabolite production in St. John's wort and controlled environment technology can allow the precise application of such specific stresses.

  • temperature stress can alter the photosynthetic efficiency and Secondary Metabolite concentrations in st john s wort
    Plant Physiology and Biochemistry, 2005
    Co-Authors: S. M. A. Zobayed, F. Afreen, Toyoki Kozai
    Abstract:

    Abstract Temperature stress is known to cause many physiological, biochemical and molecular changes in plant metabolism and possibly alter the Secondary Metabolite production in plants. The hypothesis of the current study was that temperature stress can increase the Secondary Metabolite concentrations in St. John's wort. Plants were grown under controlled environments with artificial light using cool white fluorescent lamps and CO 2 enrichment and 70-day-old plants were subjected for 15 days to different temperature treatments of 15, 20, 25, 30 and 35 °C before harvested. Major aim of the study was to increase the major Secondary Metabolites in St. John's wort by applying temperature stress and to evaluate the physiological status of the plant especially the photosynthetic efficiency and peroxidase activity of the leaf tissues exposed to different temperatures under precisely controlled environmental factors. Results revealed that relatively high (35 °C) or low (15 °C) temperatures reduced the photosynthetic efficiency of the leaves of St. John's wort plants and resulted in low CO 2 assimilation. Net photosynthetic rates and the maximal quantum efficiency of PSII photochemistry of the dark adopted leaves (ϕ p max ) decreased significantly in the leaves of plants grown under 35 or 15 °C temperature treatments. High temperature (35 °C) treatment increased the leaf total peroxidase activity and also increased the hypericin, pseudohypericin and hyperforin concentrations in the shoot tissues. These results provide the first indication that temperature is an important environmental factor to optimize the Secondary Metabolite production in St. John's wort and controlled environment technology can allow the precise application of such specific stresses.

  • Relationships between net photosynthetic rate and Secondary Metabolite contents in St. John's wort
    Plant Science, 2005
    Co-Authors: Kriengkrai Mosaleeyanon, S. M. A. Zobayed, F. Afreen, Toyoki Kozai
    Abstract:

    Abstract Hypericum perforatum L. (St. John's wort), a traditional herb with antidepressive and wound healing properties, was grown under 100, 300 and 600 μmol m −2  s −1 photosynthetic photon flux (PPF) each with 500, 1000 and 1500 μmol mol −1 CO 2 , with the objective of maximizing the biomass and Secondary Metabolite production. Plants grown in the field (1770 μmol m −2  s −1 PPF and 380 μmol mol −1 CO 2 ) were used as a control. On day 45, total fresh and dry mass, and the number of stem nodes were greatest in plants grown under 600 μmol m −2  s −1 PPF with 1500 μmol mol −1 CO 2 concentration (HH-treatment) and were 29, 30 and 4 times greater, respectively, than those of the control. Leaf net photosynthetic rate (Pn) increased with increasing PPF and/or CO 2 concentration, with the highest value occurring in the plants grown under the HH-treatment. Secondary Metabolite contents (mg/plant) in the leaf tissues were generally higher in the plants grown under the controlled environments than those in the field (control). Hypericin and pseudohypericin contents were highest in the HH-treatment, being 30 and 41 times greater, respectively, than those of the control. Hypericin and pseudohypericin contents in the leaf tissues increased with increasing Pn. The second order polynomial correlations between Pn and hypericin, and between Pn and pseudohypericin contents with R 2 of 0.82 and 0.79, respectively, were obtained. Moreover, total hypericin (hypericin + pseudohypericin) concentration (mg g −1 leaf DM) in leaf tissues was related to both PPF and CO 2 concentration as expressed by second order polynomial correlations ( R 2  = 1). Therefore, growing St. John's wort plants under a controlled environment can enhance biomass and Secondary Metabolite production by increasing net photosynthetic rate.

Gavin Sherlock - One of the best experts on this subject based on the ideXlab platform.

  • comprehensive annotation of Secondary Metabolite biosynthetic genes and gene clusters of aspergillus nidulans a fumigatus a niger and a oryzae
    BMC Microbiology, 2013
    Co-Authors: Diane O Inglis, Martha B. Arnaud, Marek S. Skrzypek, Prachi Shah, Farrell Wymore, Gustavo C. Cerqueira, Jennifer R Wortman, Jonathan Binkley, Gavin Sherlock
    Abstract:

    Background Secondary Metabolite production, a hallmark of filamentous fungi, is an expanding area of research for the Aspergilli. These compounds are potent chemicals, ranging from deadly toxins to therapeutic antibiotics to potential anti-cancer drugs. The genome sequences for multiple Aspergilli have been determined, and provide a wealth of predictive information about Secondary Metabolite production. Sequence analysis and gene overexpression strategies have enabled the discovery of novel Secondary Metabolites and the genes involved in their biosynthesis. The Aspergillus Genome Database (AspGD) provides a central repository for gene annotation and protein information for Aspergillus species. These annotations include Gene Ontology (GO) terms, phenotype data, gene names and descriptions and they are crucial for interpreting both small- and large-scale data and for aiding in the design of new experiments that further Aspergillus research.

  • Comprehensive annotation of Secondary Metabolite biosynthetic genes and gene clusters of Aspergillus nidulans, A. fumigatus, A. niger and A. oryzae
    BMC Microbiology, 2013
    Co-Authors: Diane O Inglis, Martha B. Arnaud, Marek S. Skrzypek, Prachi Shah, Farrell Wymore, Gustavo C. Cerqueira, Jennifer R Wortman, Jonathan Binkley, Gavin Sherlock
    Abstract:

    Secondary Metabolite production, a hallmark of filamentous fungi, is an expanding area of research for the Aspergilli. These compounds are potent chemicals, ranging from deadly toxins to therapeutic antibiotics to potential anti-cancer drugs. The genome sequences for multiple Aspergilli have been determined, and provide a wealth of predictive information about Secondary Metabolite production. Sequence analysis and gene overexpression strategies have enabled the discovery of novel Secondary Metabolites and the genes involved in their biosynthesis. The Aspergillus Genome Database (AspGD) provides a central repository for gene annotation and protein information for Aspergillus species. These annotations include Gene Ontology (GO) terms, phenotype data, gene names and descriptions and they are crucial for interpreting both small- and large-scale data and for aiding in the design of new experiments that further Aspergillus research. We have manually curated Biological Process GO annotations for all genes in AspGD with recorded functions in Secondary Metabolite production, adding new GO terms that specifically describe each Secondary Metabolite. We then leveraged these new annotations to predict roles in Secondary metabolism for genes lacking experimental characterization. As a starting point for manually annotating Aspergillus Secondary Metabolite gene clusters, we used antiSMASH (antibiotics and Secondary Metabolite Analysis SHell) and SMURF (Secondary Metabolite Unknown Regions Finder) algorithms to identify potential clusters in A. nidulans, A. fumigatus, A. niger and A. oryzae, which we subsequently refined through manual curation. This set of 266 manually curated Secondary Metabolite gene clusters will facilitate the investigation of novel Aspergillus Secondary Metabolites.