'Silent' Fungus Metabolism Awakened For New Natural Products
ScienceDaily (May 1, 2008) — US scientists have re-awakened ‘silent’ metabolic pathways in fungi to reveal a new range of natural products. The research could provide not only a source of new drugs, but a way to “listen to what fungi are saying” to organisms around them.
Fungi produce a wide variety of natural products, including potent toxins – for example, the amanitins, primarily responsible for the toxicity of the death cap fungus – and life-saving drugs such as penicillin. As a result, the genetics of fungi have generated much interest in recent years.
Now, Robert Cichewicz and colleagues at the University of Oklahoma, Norman, US, have shown that metabolic pathways that are normally ‘silent’ can be re-activated to make new compounds, in work published in the Royal Society of Chemistry journal Organic & Biomolecular Chemistry.
Many fungi have a wealth of genes encoding for far more natural products than they actually produce, says Cichewicz. The explanation is thought to be that when fungi do not need certain compounds, they inhibit the transcription of the DNA that codes for the proteins that make them, preventing their biosynthesis.
Knowing what these mystery compounds are could be very important for the development of new medicines, as well as for helping us to understand the ecological roles that fungi play, claims Cichewicz.
The DNA involved is inhibited by being scrunched up in a globular form called heterochromatin. To activate this DNA and turn on these ‘silent’ natural product pathways, the team decided to treat fungal cultures with small molecules that interfere with the formation of the heterochromatin – allowing the DNA to be transcripted.
To show their idea in action, the researchers took a culture of Cladosporium cladosporioides, a tidal pool fungus, and treated it separately with 5-azacytidine and suberoylanilide hydroxamic acid. Both treatments, says Cichewicz, dramatically changed the natural product output of the fungus, with two completely new natural products being isolated.
The new approach impresses Jon Clardy at the Harvard Medical School, Boston, US, who says that it could ‘greatly expand the suite of biologically active small molecules obtained from fungi’ and that it ‘capitalises on recent developments in drug discovery to increase the odds of discovering new drugs’.
The results also have important implications for research into fungi and other microorganisms, explains Cichewicz. Natural products are the means by which fungi ‘communicate’ with organisms around them, so we are in essence, he says, ‘discovering chemical means for listening to what fungi are saying’.
Journal reference: Russell Williams et al., Org. Biomol. Chem., 2008, DOI: 10.1039/b804701d
Sunday, June 29, 2008
Fungus That Produces Biofuels From Plants: Genome Sequenced
Fungus That Produces Biofuels From Plants: Genome Sequenced
ScienceDaily (May 21, 2008) — The fungus Trichoderma reesei optimally breaks down plants into simple sugars, the basic components of ethanol. The fungus's genome has recently been sequenced by researchers from the Architecture et fonction des macromolécules biologiques laboratory (CNRS/Université de la Méditerranée and Universite de Provence), working together with an American team. The results show that only a few genes are responsible for the fungus's enzymatic activity. They offer new avenues for the fabrication of second generation biofuels from plant waste.
The fungus Trichoderma reesei was discovered in the South Pacific during the Second World War, where it was damaging American military equipment and was defeating every attempt at protecting the equipment with cotton cloth. The fungus contains a number of enzymes, cellulases, with potent catalytic properties that break down plants. It is considered to be the world’s most efficient fungus at breaking down the cellulose in plant cell walls into simple sugars, which it feeds on.
After fermentation, simple sugars can easily be transformed into biofuels such as ethanol. First generation agrofuels, made from grain or from beet, have certain limitations. Second generation biofuels, made from foresting and agricultural waste (tree cuttings, corn cobs, straw, etc.) do not have these limitations, as they complement pre-established agricultural activity, have a better CO2 balance, et don’t interfere with the agro-alimentary cycle. To produce these second generation biofuels, industrialists are looking to develop fungus strains capable of producing a cocktail of cellulases and hemicellulases at a concentration of 50 g/l. Trichoderma reesei is the choice organism for most projects in this field.
Bernard Henrissat’s glycogenomic team at the Architecture et fonction des macromolécules biologiques lab specializes in the study of enzymes which break down sugars.* In order to learn more about the incredible enzymatic activity of Trichoderma reesei, they assayed its genome. They found that the fungus has an unexpectedly small number of genes encoding cellulases (hemicellulases and pectinases), many fewer in fact than in usually found in fungi capable of breaking down plant cell walls. Moreover, the fungus has no or very little enzymatic activity allowing the digestion of specific components in the cell wall.
This was first interpreted as bad news, but the limitations of this model organism are now being seen as something positive. The fungus’s enzyme cocktail lends itself to numerous genetic modifications, and researchers are looking into which other enzymes can be added to the fungus’s gene sequence in order to make it even more efficient at producing bioethanol.
*The laboratory has a perfected Carbohydrate-Active Enzymes (CAZy) database which describes a number of enzyme families which form and destroy bonds between sugars.
--------------------------------------------------------------------------------
Journal reference:
Diego Martinez, Randy M Berka, Bernard Henrissat, Markku Saloheimo, Mikko Arvas, Scott E Baker, Jarod Chapman, Olga Chertkov, Pedro M Coutinho, Dan Cullen, Etienne G J Danchin, Igor V Grigoriev, Paul Harris, Melissa Jackson, Christian P Kubicek, Cliff S Han, Isaac Ho, Luis F Larrondo, Alfredo Lopez de Leon, Jon K Magnuson, Sandy Merino, Monica Misra, Beth Nelson, Nicholas Putnam, Barbara Robbertse, Asaf A Salamov, Monika Schmoll, Astrid Terry, Nina Thayer, Ann Westerholm-Parvinen, Conrad L Schoch, Jian Yao, Ravi Barbote, Mary Anne Nelson, Chris Detter, David Bruce, Cheryl R Kuske, Gary Xie, Paul Richardson, Daniel S Rokhsar, Susan M Lucas, Edward M Rubin, Nigel Dunn-Coleman, Michael Ward & Thomas S Brettin. Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina). Nature Biotechnology 26, 553 - 560 (2008) 4 May 2008 doi:10.1038/nbt1403 [link]
Adapted from materials provided by CNRS.
ScienceDaily (May 21, 2008) — The fungus Trichoderma reesei optimally breaks down plants into simple sugars, the basic components of ethanol. The fungus's genome has recently been sequenced by researchers from the Architecture et fonction des macromolécules biologiques laboratory (CNRS/Université de la Méditerranée and Universite de Provence), working together with an American team. The results show that only a few genes are responsible for the fungus's enzymatic activity. They offer new avenues for the fabrication of second generation biofuels from plant waste.
The fungus Trichoderma reesei was discovered in the South Pacific during the Second World War, where it was damaging American military equipment and was defeating every attempt at protecting the equipment with cotton cloth. The fungus contains a number of enzymes, cellulases, with potent catalytic properties that break down plants. It is considered to be the world’s most efficient fungus at breaking down the cellulose in plant cell walls into simple sugars, which it feeds on.
After fermentation, simple sugars can easily be transformed into biofuels such as ethanol. First generation agrofuels, made from grain or from beet, have certain limitations. Second generation biofuels, made from foresting and agricultural waste (tree cuttings, corn cobs, straw, etc.) do not have these limitations, as they complement pre-established agricultural activity, have a better CO2 balance, et don’t interfere with the agro-alimentary cycle. To produce these second generation biofuels, industrialists are looking to develop fungus strains capable of producing a cocktail of cellulases and hemicellulases at a concentration of 50 g/l. Trichoderma reesei is the choice organism for most projects in this field.
Bernard Henrissat’s glycogenomic team at the Architecture et fonction des macromolécules biologiques lab specializes in the study of enzymes which break down sugars.* In order to learn more about the incredible enzymatic activity of Trichoderma reesei, they assayed its genome. They found that the fungus has an unexpectedly small number of genes encoding cellulases (hemicellulases and pectinases), many fewer in fact than in usually found in fungi capable of breaking down plant cell walls. Moreover, the fungus has no or very little enzymatic activity allowing the digestion of specific components in the cell wall.
This was first interpreted as bad news, but the limitations of this model organism are now being seen as something positive. The fungus’s enzyme cocktail lends itself to numerous genetic modifications, and researchers are looking into which other enzymes can be added to the fungus’s gene sequence in order to make it even more efficient at producing bioethanol.
*The laboratory has a perfected Carbohydrate-Active Enzymes (CAZy) database which describes a number of enzyme families which form and destroy bonds between sugars.
--------------------------------------------------------------------------------
Journal reference:
Diego Martinez, Randy M Berka, Bernard Henrissat, Markku Saloheimo, Mikko Arvas, Scott E Baker, Jarod Chapman, Olga Chertkov, Pedro M Coutinho, Dan Cullen, Etienne G J Danchin, Igor V Grigoriev, Paul Harris, Melissa Jackson, Christian P Kubicek, Cliff S Han, Isaac Ho, Luis F Larrondo, Alfredo Lopez de Leon, Jon K Magnuson, Sandy Merino, Monica Misra, Beth Nelson, Nicholas Putnam, Barbara Robbertse, Asaf A Salamov, Monika Schmoll, Astrid Terry, Nina Thayer, Ann Westerholm-Parvinen, Conrad L Schoch, Jian Yao, Ravi Barbote, Mary Anne Nelson, Chris Detter, David Bruce, Cheryl R Kuske, Gary Xie, Paul Richardson, Daniel S Rokhsar, Susan M Lucas, Edward M Rubin, Nigel Dunn-Coleman, Michael Ward & Thomas S Brettin. Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina). Nature Biotechnology 26, 553 - 560 (2008) 4 May 2008 doi:10.1038/nbt1403 [link]
Adapted from materials provided by CNRS.
Fungi Have A Hand In Depleted Uranium's Environmental Fate
Fungi Have A Hand In Depleted Uranium's Environmental Fate
ScienceDaily (May 6, 2008) — Fungi may have an important role to play in the fate of potentially dangerous depleted uranium left in the environment after recent war campaigns, according to a new report in the May 6th issue of Current Biology, a publication of Cell Press.
The researchers found evidence that fungi can "lock" depleted uranium into a mineral form that may be less likely to find its way into plants, animals, or the water supply.
"This work provides yet another example of the incredible properties of microorganisms in effecting transformations of metals and minerals in the natural environment," said Geoffrey Gadd of the University of Dundee in Scotland. "Because fungi are perfectly suited as biogeochemical agents, often dominate the biota in polluted soils, and play a major role in the establishment and survival of plants through their association with roots, fungal-based approaches should not be neglected in remediation attempts for metal-polluted soils."
The testing of depleted-uranium ammunition and its recent use in Iraq and the Balkans has led to contamination of the environment with the unstable metal, Gadd explained. Depleted uranium differs from natural uranium in the balance of isotopes it contains. It is the byproduct of uranium enrichment for use in nuclear reactors or nuclear weapons and is valued for its very high density. Although less radioactive than natural uranium, depleted uranium is just as toxic and poses a threat to people.
In the new study, the researchers found that free-living and plant symbiotic (mycorrhizal) fungi can colonize depleted-uranium surfaces and transform the metal into uranyl phosphate minerals.
While they probably still pose some threat, he said, "The fungal-produced minerals are capable of long-term uranium retention, so this may help prevent uptake of uranium by plants, animals, and microbes. It might also prevent the spent uranium from leaching out from the soil."
Gadd said that a combination of environmental and biological factors is involved in the process. First, the unstable uranium metal gets coated with a layer of oxides. Moisture in the environment also "corrodes" the depleted uranium, encouraging fungal colonization and growth. While the fungi grow, they produce acidic substances, which corrode the depleted uranium even further. Some of the substances produced include organic acids that convert the uranium into a form that the fungi can take up or that can interact with other compounds. Ultimately, he said, the interaction of soluble forms of uranium with phosphate leads to the formation of the new uranium minerals that get deposited around the fungal biomass.
"We have shown for the first time that fungi can transform metallic uranium into minerals, which are capable of long-term uranium retention," the researchers concluded. "This phenomenon could be relevant to the future development of various remediation and revegetation techniques for uranium-polluted soils."
The researchers include Marina Fomina of University of Dundee in Dundee, Scotland; John M. Charnock of Synchrotron Radiation Source (SRS) Daresbury Laboratory in Daresbury, Warrington, Cheshire; Stephen Hillier of Macaulay Institute in Craigiebuckler, Aberdeen, Scotland; Rebeca Alvarez and Francis Livens of University of Manchester in Manchester, UK; and Geoffrey M. Gadd of University of Dundee in Dundee, Scotland.
This work was financially supported by the MOD/NERC DU Programme (Grant NE/C506799/1), CCLRC Daresbury SRS (SRS beamtime allocation 45100), and the Scottish Executive Environmental and Rural Affairs Department (SEERAD).
Journal reference: Fomina et al.: "Role of fungi in the biogeochemical fate of depleted uranium." Publishing in Current Biology 18, R375 --R377, May 6, 2008.
ScienceDaily (May 6, 2008) — Fungi may have an important role to play in the fate of potentially dangerous depleted uranium left in the environment after recent war campaigns, according to a new report in the May 6th issue of Current Biology, a publication of Cell Press.
The researchers found evidence that fungi can "lock" depleted uranium into a mineral form that may be less likely to find its way into plants, animals, or the water supply.
"This work provides yet another example of the incredible properties of microorganisms in effecting transformations of metals and minerals in the natural environment," said Geoffrey Gadd of the University of Dundee in Scotland. "Because fungi are perfectly suited as biogeochemical agents, often dominate the biota in polluted soils, and play a major role in the establishment and survival of plants through their association with roots, fungal-based approaches should not be neglected in remediation attempts for metal-polluted soils."
The testing of depleted-uranium ammunition and its recent use in Iraq and the Balkans has led to contamination of the environment with the unstable metal, Gadd explained. Depleted uranium differs from natural uranium in the balance of isotopes it contains. It is the byproduct of uranium enrichment for use in nuclear reactors or nuclear weapons and is valued for its very high density. Although less radioactive than natural uranium, depleted uranium is just as toxic and poses a threat to people.
In the new study, the researchers found that free-living and plant symbiotic (mycorrhizal) fungi can colonize depleted-uranium surfaces and transform the metal into uranyl phosphate minerals.
While they probably still pose some threat, he said, "The fungal-produced minerals are capable of long-term uranium retention, so this may help prevent uptake of uranium by plants, animals, and microbes. It might also prevent the spent uranium from leaching out from the soil."
Gadd said that a combination of environmental and biological factors is involved in the process. First, the unstable uranium metal gets coated with a layer of oxides. Moisture in the environment also "corrodes" the depleted uranium, encouraging fungal colonization and growth. While the fungi grow, they produce acidic substances, which corrode the depleted uranium even further. Some of the substances produced include organic acids that convert the uranium into a form that the fungi can take up or that can interact with other compounds. Ultimately, he said, the interaction of soluble forms of uranium with phosphate leads to the formation of the new uranium minerals that get deposited around the fungal biomass.
"We have shown for the first time that fungi can transform metallic uranium into minerals, which are capable of long-term uranium retention," the researchers concluded. "This phenomenon could be relevant to the future development of various remediation and revegetation techniques for uranium-polluted soils."
The researchers include Marina Fomina of University of Dundee in Dundee, Scotland; John M. Charnock of Synchrotron Radiation Source (SRS) Daresbury Laboratory in Daresbury, Warrington, Cheshire; Stephen Hillier of Macaulay Institute in Craigiebuckler, Aberdeen, Scotland; Rebeca Alvarez and Francis Livens of University of Manchester in Manchester, UK; and Geoffrey M. Gadd of University of Dundee in Dundee, Scotland.
This work was financially supported by the MOD/NERC DU Programme (Grant NE/C506799/1), CCLRC Daresbury SRS (SRS beamtime allocation 45100), and the Scottish Executive Environmental and Rural Affairs Department (SEERAD).
Journal reference: Fomina et al.: "Role of fungi in the biogeochemical fate of depleted uranium." Publishing in Current Biology 18, R375 --R377, May 6, 2008.
Saturday, April 5, 2008
" A surge of volcanic activity around 65 million years ago could have triggered a mass extinction by pumping sulphur and chlorine into the atmosphere."
Dinosaur killer found in volcanic bubbles. New Scientist. 01 April 2008. Available from: http://www.newscientist.com/channel/life/mg19726494.700-dinosaur-killer-found-in-volcanic-bubbles.html.
What where the sulfur loving bacteria doing at this time?
What impact did this increase of sulfur have on the sulfur chemolithotrophic bacteria?
Dinosaur killer found in volcanic bubbles. New Scientist. 01 April 2008. Available from: http://www.newscientist.com/channel/life/mg19726494.700-dinosaur-killer-found-in-volcanic-bubbles.html.
What where the sulfur loving bacteria doing at this time?
What impact did this increase of sulfur have on the sulfur chemolithotrophic bacteria?
Wednesday, March 5, 2008
Great Podcast show notes
BBC Radio 4
THE MATERIAL WORLD
PROGRAMME DETAILS
Thursday 28 February 2008
Fungi Exploitation
Science is going back to basics ...
We look at how more than 28,000 strains of fungus held in the UK’s national collection are becoming the focus of research seeking new antibacterial drugs.
The collection has great roots – it still holds an original sample of Sir Alexander Fleming’s penicillin.
Quentin Cooper is joined by Dr Joan Kelley, Executive Director Bioservices, CABI and Professor Peter Bramley, Head of the School of Biological Sciences Royal Holloway, University of London.
Electron Microscopes
We meet the scientists who are using the advances in microscopes used to make computer chips to explore the world of biological systems - at the atomic level.
This new nano microscope technology is allowing scientists to move clusters of atoms while they actually look at them, and to create three dimensional images of biological systems ten thousands times smaller than the diameter of a human hair.
Can this nano-vision help in the fight against some of the most dangerous diseases - like cancer?
Quentin is joined by Dr Andy Bushby, Director of NanoVision Centre, Queen Mary, University of London and by Dr Lucy Collinson, Head of Electron Microscopy, London Research Institute, Cancer Research UK
THE MATERIAL WORLD
PROGRAMME DETAILS
Thursday 28 February 2008
Fungi Exploitation
Science is going back to basics ...
We look at how more than 28,000 strains of fungus held in the UK’s national collection are becoming the focus of research seeking new antibacterial drugs.
The collection has great roots – it still holds an original sample of Sir Alexander Fleming’s penicillin.
Quentin Cooper is joined by Dr Joan Kelley, Executive Director Bioservices, CABI and Professor Peter Bramley, Head of the School of Biological Sciences Royal Holloway, University of London.
Electron Microscopes
We meet the scientists who are using the advances in microscopes used to make computer chips to explore the world of biological systems - at the atomic level.
This new nano microscope technology is allowing scientists to move clusters of atoms while they actually look at them, and to create three dimensional images of biological systems ten thousands times smaller than the diameter of a human hair.
Can this nano-vision help in the fight against some of the most dangerous diseases - like cancer?
Quentin is joined by Dr Andy Bushby, Director of NanoVision Centre, Queen Mary, University of London and by Dr Lucy Collinson, Head of Electron Microscopy, London Research Institute, Cancer Research UK
Tuesday, February 26, 2008
Sunday, February 17, 2008
Stop drinking coffee and go to bed early for better reproductive success?
The effects of male age on sperm DNA damage in healthy non-smokers
Author(s): Schmid TE (Schmid, T. E.), Eskenazi B (Eskenazi, B.), Baumgartner A (Baumgartner, A.), Marchetti F (Marchetti, F.), Young S (Young, S.), Weldon R (Weldon, R.), Anderson D (Anderson, D.), Wyrobek AJ (Wyrobek, A. J.)
Source: HUMAN REPRODUCTION Volume: 22 Issue: 1 Pages: 180-187 Published: 2007
Times Cited: 4 References: 64
Abstract: BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed > 3 cups coffee per day had similar to 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.
Document Type: Article
Language: English
Author Keywords: ageing; caffeine; Comet; DNA damage; sperm
KeyWords Plus: CHROMATIN-STRUCTURE ASSAY; COMET ASSAY; PATERNAL-AGE; SEMEN QUALITY; CHROMOSOMAL-ABERRATIONS; SPONTANEOUS MUTATION; ANTIOXIDANT INTAKE; CIGARETTE-SMOKING; OXIDATIVE STRESS; MOUSE ZYGOTES
Addresses: Wyrobek, AJ (reprint author), Lawrence Berkeley Lab, Life Sci Div, Berkeley, CA USA
Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA USA
Univ Bradford, Dept Biomed Sci, Bradford, W Yorkshire England
Publisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
Subject Category: Obstetrics & Gynecology; Reproductive Biology
IDS Number: 120EA
ISSN: 0268-1161
DOI: 10.1093/humrep/del338
Author(s): Schmid TE (Schmid, T. E.), Eskenazi B (Eskenazi, B.), Baumgartner A (Baumgartner, A.), Marchetti F (Marchetti, F.), Young S (Young, S.), Weldon R (Weldon, R.), Anderson D (Anderson, D.), Wyrobek AJ (Wyrobek, A. J.)
Source: HUMAN REPRODUCTION Volume: 22 Issue: 1 Pages: 180-187 Published: 2007
Times Cited: 4 References: 64
Abstract: BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed > 3 cups coffee per day had similar to 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.
Document Type: Article
Language: English
Author Keywords: ageing; caffeine; Comet; DNA damage; sperm
KeyWords Plus: CHROMATIN-STRUCTURE ASSAY; COMET ASSAY; PATERNAL-AGE; SEMEN QUALITY; CHROMOSOMAL-ABERRATIONS; SPONTANEOUS MUTATION; ANTIOXIDANT INTAKE; CIGARETTE-SMOKING; OXIDATIVE STRESS; MOUSE ZYGOTES
Addresses: Wyrobek, AJ (reprint author), Lawrence Berkeley Lab, Life Sci Div, Berkeley, CA USA
Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA USA
Univ Bradford, Dept Biomed Sci, Bradford, W Yorkshire England
Publisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
Subject Category: Obstetrics & Gynecology; Reproductive Biology
IDS Number: 120EA
ISSN: 0268-1161
DOI: 10.1093/humrep/del338
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