DOCSLIB.ORG

Biosynthesis and Function of Secondary Metabolites

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Biosynthesis and function of secondary metabolites Edited by Jeroen S. Dickschat Generated on 11 October 2021, 10:46 Imprint Beilstein Journal of Organic Chemistry www.bjoc.org ISSN 1860-5397 Email: [email protected] The Beilstein Journal of Organic Chemistry is published by the Beilstein-Institut zur Förderung der Chemischen Wissenschaften. This thematic issue, published in the Beilstein Beilstein-Institut zur Förderung der Journal of Organic Chemistry, is copyright the Chemischen Wissenschaften Beilstein-Institut zur Förderung der Chemischen Trakehner Straße 7–9 Wissenschaften. The copyright of the individual 60487 Frankfurt am Main articles in this document is the property of their Germany respective authors, subject to a Creative www.beilstein-institut.de Commons Attribution (CC-BY) license. Biosynthesis and function of secondary metabolites Jeroen S. Dickschat Editorial Open Access Address: Beilstein J. Org. Chem. 2011, 7, 1620–1621. Institut für Organische Chemie, Technische Universität doi:10.3762/bjoc.7.190 Carolo-Wilhelmina zu Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany Received: 20 October 2011 Accepted: 25 October 2011 Email: Published: 05 December 2011 Jeroen S. Dickschat - [email protected] This article is part of the Thematic Series "Biosynthesis and function of secondary metabolites". Guest Editor: J. S. Dickschat © 2011 Dickschat; licensee Beilstein-Institut. License and terms: see end of document. Natural products have long been used by humans owing to their situation started to change at the beginning of the 19th century, beneficial effects. Indulgences such as coffee and tea, with their when Friedrich Wilhelm Adam Sertürner (1783–1841) first moderate stimulatory properties, have a long cultural tradition isolated morphine from opium, naming it after Morpheus, the and are today some of the most important agricultural products Greek god of dreams and demonstrating its activity in self-tests, worldwide. Other drugs have much stronger impacts on the as was typical practice during these early times of chemistry. A central nervous system. For example, coca was originally used likewise important discovery was made by Alexander Fleming by the Inca civilisation because of its strong stimulatory effects, (1881–1955), who isolated the antibiotic penicillin from the which result in feelings of happiness and euphoria. Opium was mould Penicillium notatum in a groundbreaking contribution, used by many ancient cultures as an efficient analgesic, but this which was awarded the Nobel Prize in 1945. also illustrates one of the first examples of drug abuse as it was used by warriors as an anxiolytic when girding their loins. The discovery of new bioactive natural products is still a fascin- Besides their pleasant traits these highly active drugs have ating field in organic chemistry as demonstrated by the recent adverse side effects, including most importantly an extremely paradigms of the anticancer drug epothilon, the immunosup- high potential to cause addiction in combination with physical pressant rapamycin, or the proteasome inhibitor salinospor- and mental prostration upon long-term abuse. Therefore, the amide, to name but a few of hundreds of possible examples. production, importation, trading, and possession of these drugs Finding new secondary metabolites is a prerequisite for the are today under strict control by public authorities. Another development of novel pharmaceuticals, and this is an especially historically interesting example of drug misuse is given by the urgent task in the case of antibiotics due to the rapid spreading death penalty imposed on Socrates in 399 B.C., carried out by of bacterial resistances and the emergence of multiresistant the forced ingestion of the proverbial cup of hemlock. pathogenic strains, which poses severe clinical problems in the treatment of infectious diseases. This Thematic Series on the These traditional and historical examples of the usage of biosynthesis and function of secondary metabolites deals with bioactive natural products all originated in the ancient cultures, the discovery of new biologically active compounds from all without any knowledge about the underlying chemistry. This kinds of sources, including plants, bacteria, and fungi, and also 1620 Beilstein J. Org. Chem. 2011, 7, 1620–1621. with their biogenesis. Biosynthetic aspects are closely related to functional investigations, because a deep understanding of License and Terms metabolic pathways to natural products, not only on a chemical, This is an Open Access article under the terms of the but also on a genetic and enzymatic level, allows for the expres- Creative Commons Attribution License sion of whole biosynthetic gene clusters in heterologous hosts. (http://creativecommons.org/licenses/by/2.0), which This technique can make interesting, new secondary metabol- permits unrestricted use, distribution, and reproduction in ites available from unculturable microorganisms, or may be any medium, provided the original work is properly cited. used to optimise their availability by fermentation, for further research and also for production in the pharmaceutical industry. The license is subject to the Beilstein Journal of Organic Especially fascinating is the intrinsic logic of the polyketide and Chemistry terms and conditions: nonribosomal peptide biosynthetic machineries, which is (http://www.beilstein-journals.org/bjoc) strongly correlated with the logic of fatty acid biosynthesis as part of the primary metabolism. Insights into the mechanisms of The definitive version of this article is the electronic one modular polyketide and nonribosomal peptide assembly lines which can be found at: open up the possibility for direct modifications, e.g., of oxi- doi:10.3762/bjoc.7.190 dation states of the natural product’s carbon backbone by simple domain knockouts within the responsible megasyn- thases, or the introduction of a variety of alternative biosyn- thetic starters by mutasynthesis approaches, thus leading to new variants of known metabolites, which may have improved prop- erties for therapeutic use. Another interesting aspect is the usage of enzymes in chemical transformations, which can provide synthetic organic chemists with an efficient access route to typically chiral building blocks that may otherwise be difficult to obtain. It is my great pleasure to thank all of the contributors to this Thematic Series, the staff of the Beilstein-Institut, and my esteemed colleague and teacher Prof. Henning Hopf (Braunschweig) for opening the opportunity to guest-edit the present issue. Enjoy reading it! Jeroen S. Dickschat Braunschweig, October 2011 1621 Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes Jan-Christoph Kehr, Douglas Gatte Picchi and Elke Dittmann* Review Open Access Address: Beilstein J. Org. Chem. 2011, 7, 1622–1635. University of Potsdam, Institute for Biochemistry and Biology, doi:10.3762/bjoc.7.191 Karl-Liebknecht-Str. 24/25, 14476 Potsdam-Golm, Germany Received: 22 July 2011 Email: Accepted: 19 September 2011 Jan-Christoph Kehr - [email protected]; Douglas Gatte Picchi - Published: 05 December 2011 [email protected]; Elke Dittmann* - [email protected] This article is part of the Thematic Series "Biosynthesis and function of * Corresponding author secondary metabolites". Keywords: Guest Editor: J. S. Dickschat cyanobacteria; natural products; NRPS; PKS; ribosomal peptides © 2011 Kehr et al; licensee Beilstein-Institut. License and terms: see end of document. Abstract Cyanobacteria are prolific producers of natural products. Investigations into the biochemistry responsible for the formation of these compounds have revealed fascinating mechanisms that are not, or only rarely, found in other microorganisms. In this article, we survey the biosynthetic pathways of cyanobacteria isolated from freshwater, marine and terrestrial habitats. We especially empha- size modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathways and highlight the unique enzyme mechanisms that were elucidated or can be anticipated for the individual products. We further include ribosomal natural products and UV-absorbing pigments from cyanobacteria. Mechanistic insights obtained from the biochemical studies of cyanobacterial pathways can inspire the development of concepts for the design of bioactive compounds by synthetic-biology approaches in the future. Introduction The role of cyanobacteria in natural product research Cyanobacteria flourish in diverse ecosystems and play an enor- [2] (Figure 1). Other cyanobacteria show a strong tendency for mous role in the biogeochemical cycles on earth. They are mass developments during summer months, so-called blooms found in marine, freshwater and terrestrial environments and [3] (Figure 1). Cyanobacteria do not belong to the established even populate such extreme habitats as the Antarctic or hot sources of natural products and are only incidentally screened springs [1]. Due to their capability to fix nitrogen from the by pharmaceutical industries. For a long time, natural product atmosphere some species are attractive partners in symbioses research on cyanobacteria was mostly focused on toxins, in par- 1622 Beilstein J. Org. Chem. 2011, 7, 1622–1635. Figure 1: Cyanobacteria proliferate in diverse habitats. A) Bloom-forming freshwater cyanobacteria of the genus Microcystis. B) Roots of cyanobacte- rial symbiosis host Cycas circinalis. C) Terrestrial cyanobacteria living in corraloid
Recommended publications
  • Investigating the Initial Steps in the Biosynthesis of Cyanobacterial Sunscreen Scytonemin

    Investigating the Initial Steps in the Biosynthesis of Cyanobacterial Sunscreen Scytonemin

    Investigating the Initial Steps in the Biosynthesis of Cyanobacterial Sunscreen Scytonemin The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Balskus, Emily P., and Christopher T. Walsh. 2008. “Investigating the Initial Steps in the Biosynthesis of Cyanobacterial Sunscreen Scytonemin.” Journal of the American Chemical Society 130 (46) (November 19): 15260–15261. Published Version doi:10.1021/ja807192u Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:12153245 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Open Access Policy Articles, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#OAP NIH Public Access Author Manuscript J Am Chem Soc. Author manuscript; available in PMC 2009 November 19. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: J Am Chem Soc. 2008 November 19; 130(46): 15260±15261. doi:10.1021/ja807192u. Investigating the Initial Steps in the Biosynthesis of Cyanobacterial Sunscreen Scytonemin Emily P. Balskus and Christopher T. Walsh Contribution from the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115 Photosynthetic cyanobacteria have evolved a variety of strategies for coping with exposure to damaging solar UV radiation,1 including DNA repair processes,2 UV avoidance behavior,3 and the synthesis of radiation-absorbing pigments.4 Scytonemin (1) is the most widespread and extensively characterized cyanobacterial sunscreen.5 This lipid soluble alkaloid accumulates in the extracellular sheaths of cyanobacteria upon exposure to UV-A light, where 6 it absorbs further incident radiation λmax = 384 nm).
  • Bacteria Increase Arid-Land Soil Surface Temperature Through the Production of Sunscreens

    Bacteria Increase Arid-Land Soil Surface Temperature Through the Production of Sunscreens

    Lawrence Berkeley National Laboratory Recent Work Title Bacteria increase arid-land soil surface temperature through the production of sunscreens. Permalink https://escholarship.org/uc/item/0gm2g8mx Journal Nature communications, 7(1) ISSN 2041-1723 Authors Couradeau, Estelle Karaoz, Ulas Lim, Hsiao Chien et al. Publication Date 2016-01-20 DOI 10.1038/ncomms10373 Peer reviewed eScholarship.org Powered by the California Digital Library University of California ARTICLE Received 9 Jun 2015 | Accepted 3 Dec 2015 | Published 20 Jan 2016 DOI: 10.1038/ncomms10373 OPEN Bacteria increase arid-land soil surface temperature through the production of sunscreens Estelle Couradeau1, Ulas Karaoz2, Hsiao Chien Lim2, Ulisses Nunes da Rocha2,w, Trent Northen3, Eoin Brodie2,4 & Ferran Garcia-Pichel1,3 Soil surface temperature, an important driver of terrestrial biogeochemical processes, depends strongly on soil albedo, which can be significantly modified by factors such as plant cover. In sparsely vegetated lands, the soil surface can be colonized by photosynthetic microbes that build biocrust communities. Here we use concurrent physical, biochemical and microbiological analyses to show that mature biocrusts can increase surface soil temperature by as much as 10 °C through the accumulation of large quantities of a secondary metabolite, the microbial sunscreen scytonemin, produced by a group of late-successional cyanobacteria. Scytonemin accumulation decreases soil albedo significantly. Such localized warming has apparent and immediate consequences for the soil microbiome, inducing the replacement of thermosensitive bacterial species with more thermotolerant forms. These results reveal that not only vegetation but also microorganisms are a factor in modifying terrestrial albedo, potentially impacting biosphere feedbacks on past and future climate, and call for a direct assessment of such effects at larger scales.
  • Small Organic Molecules As Tunable Tools for Biology

    Small Organic Molecules As Tunable Tools for Biology

    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2015 Small Organic Molecules as Tunable Tools for Biology Unzue Lopez, Andrea Abstract: Drug discovery and development is a very challenging interdisciplinary endeavor that needs the contribution of medical doctors, biologists, chemists, X-ray crystallographers, and computer scientists, among many others, in order to be successful. The first part of this Ph. D. thesis focuses onthe development of EphB4 receptor tyrosine kinase inhibitors. EphB4 has been linked to angiogenesis, which involves the formation of new blood vessels supplying tumor cells with the necessary nutrients. Protein kinases play a key role in cell signaling by phosphorylating specific proteins and thus, the inhibition of their enzymatic activity by small organic molecules has been widely explored in drug design. In this work, the biological properties of an EphB4 inhibitor identified by computer simulations were improved bythe synthesis of several analogues. Their binding affinities were characterized by an array of biochemical and cell based assays, concluding with the validation of one of the most promising derivatives in an in vivo cancer xenograft model. The second part of the thesis deals with the development of novel bromodomain ligands starting from a micromolar potent in silico discovered hit. Bromodomain proteins are epigenetic readers that constitute an emerging topic in the field of drug discovery and are thus considered asvery attractive targets for the development of novel therapeutic drugs. A careful, structure-based design of analogues resulted in the discovery of nanomolar potent CREBBP ligands with an unprecedented selectivity profile among the bromodomain protein family.
  • Thi Thu Tram NGUYEN

    Thi Thu Tram NGUYEN

    ANNÉE 2014 THÈSE / UNIVERSITÉ DE RENNES 1 sous le sceau de l’Université Européenne de Bretagne pour le grade de DOCTEUR DE L’UNIVERSITÉ DE RENNES 1 Mention : Chimie Ecole doctorale Sciences De La Matière Thi Thu Tram NGUYEN Préparée dans l’unité de recherche UMR CNRS 6226 Equipe PNSCM (Produits Naturels Synthèses Chimie Médicinale) (Faculté de Pharmacie, Université de Rennes 1) Screening of Thèse soutenue à Rennes le 19 décembre 2014 mycosporine-like devant le jury composé de : compounds in the Marie-Dominique GALIBERT Professeur à l’Université de Rennes 1 / Examinateur Dermatocarpon genus. Holger THÜS Conservateur au Natural History Museum Londres / Phytochemical study Rapporteur Erwan AR GALL of the lichen Maître de conférences à l’Université de Bretagne Occidentale / Rapporteur Dermatocarpon luridum Kim Phi Phung NGUYEN Professeur à l’Université des sciences naturelles (With.) J.R. Laundon. d’Hô-Chi-Minh-Ville Vietnam / Examinateur Marylène CHOLLET-KRUGLER Maître de conférences à l’Université de Rennes1 / Co-directeur de thèse Joël BOUSTIE Professeur à l’Université de Rennes 1 / Directeur de thèse Remerciements En premier lieu, je tiens à remercier Monsieur le Dr Holger Thüs et Monsieur le Dr Erwan Ar Gall d’avoir accepté d’être les rapporteurs de mon manuscrit, ainsi que Madame la Professeure Marie-Dominique Galibert d’avoir accepté de participer à ce jury de thèse. J’exprime toute ma gratitude au Dr Marylène Chollet-Krugler pour avoir guidé mes pas dès les premiers jours et tout au long de ces trois années. Je la remercie particulièrement pour sa disponibilité et sa grande gentillesse, son écoute et sa patience.
  • Cultural Heritage Series

    Cultural Heritage Series

    VOLUME 4 PART 2 MEMOIRS OF THE QUEENSLAND MUSEUM CULTURAL HERITAGE SERIES 17 OCTOBER 2008 © The State of Queensland (Queensland Museum) 2008 PO Box 3300, South Brisbane 4101, Australia Phone 06 7 3840 7555 Fax 06 7 3846 1226 Email [email protected] Website www.qm.qld.gov.au National Library of Australia card number ISSN 1440-4788 NOTE Papers published in this volume and in all previous volumes of the Memoirs of the Queensland Museum may be reproduced for scientific research, individual study or other educational purposes. Properly acknowledged quotations may be made but queries regarding the republication of any papers should be addressed to the Editor in Chief. Copies of the journal can be purchased from the Queensland Museum Shop. A Guide to Authors is displayed at the Queensland Museum web site A Queensland Government Project Typeset at the Queensland Museum CHAPTER 4 HISTORICAL MUA ANNA SHNUKAL Shnukal, A. 2008 10 17: Historical Mua. Memoirs of the Queensland Museum, Cultural Heritage Series 4(2): 61-205. Brisbane. ISSN 1440-4788. As a consequence of their different origins, populations, legal status, administrations and rates of growth, the post-contact western and eastern Muan communities followed different historical trajectories. This chapter traces the history of Mua, linking events with the family connections which always existed but were down-played until the second half of the 20th century. There are four sections, each relating to a different period of Mua’s history. Each is historically contextualised and contains discussions on economy, administration, infrastructure, health, religion, education and population. Totalai, Dabu, Poid, Kubin, St Paul’s community, Port Lihou, church missions, Pacific Islanders, education, health, Torres Strait history, Mua (Banks Island).
  • Health Effects Support Document for Perfluorooctanoic Acid (PFOA)

    Health Effects Support Document for Perfluorooctanoic Acid (PFOA)

    United States Office of Water EPA 822-R-16-003 Environmental Protection Mail Code 4304T May 2016 Agency Health Effects Support Document for Perfluorooctanoic Acid (PFOA) Perfluorooctanoic Acid – May 2016 i Health Effects Support Document for Perfluorooctanoic Acid (PFOA) U.S. Environmental Protection Agency Office of Water (4304T) Health and Ecological Criteria Division Washington, DC 20460 EPA Document Number: 822-R-16-003 May 2016 Perfluorooctanoic Acid – May 2016 ii BACKGROUND The Safe Drinking Water Act (SDWA), as amended in 1996, requires the Administrator of the U.S. Environmental Protection Agency (EPA) to periodically publish a list of unregulated chemical contaminants known or anticipated to occur in public water systems and that may require regulation under SDWA. The SDWA also requires the Agency to make regulatory determinations on at least five contaminants on the Contaminant Candidate List (CCL) every 5 years. For each contaminant on the CCL, before EPA makes a regulatory determination, the Agency needs to obtain sufficient data to conduct analyses on the extent to which the contaminant occurs and the risk it poses to populations via drinking water. Ultimately, this information will assist the Agency in determining the most appropriate course of action in relation to the contaminant (e.g., developing a regulation to control it in drinking water, developing guidance, or deciding not to regulate it). The PFOA health assessment was initiated by the Office of Water, Office of Science and Technology in 2009. The draft Health Effects Support Document for Perfluoroctanoic Acid (PFOA) was completed in 2013 and released for public comment in February 2014.
  • Marine Natural Products: a Source of Novel Anticancer Drugs

    Marine Natural Products: a Source of Novel Anticancer Drugs

    marine drugs Review Marine Natural Products: A Source of Novel Anticancer Drugs Shaden A. M. Khalifa 1,2, Nizar Elias 3, Mohamed A. Farag 4,5, Lei Chen 6, Aamer Saeed 7 , Mohamed-Elamir F. Hegazy 8,9, Moustafa S. Moustafa 10, Aida Abd El-Wahed 10, Saleh M. Al-Mousawi 10, Syed G. Musharraf 11, Fang-Rong Chang 12 , Arihiro Iwasaki 13 , Kiyotake Suenaga 13 , Muaaz Alajlani 14,15, Ulf Göransson 15 and Hesham R. El-Seedi 15,16,17,18,* 1 Clinical Research Centre, Karolinska University Hospital, Novum, 14157 Huddinge, Stockholm, Sweden 2 Department of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE 106 91 Stockholm, Sweden 3 Department of Laboratory Medicine, Faculty of Medicine, University of Kalamoon, P.O. Box 222 Dayr Atiyah, Syria 4 Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr el Aini St., P.B. 11562 Cairo, Egypt 5 Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, 11835 New Cairo, Egypt 6 College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China 7 Department of Chemitry, Quaid-i-Azam University, Islamabad 45320, Pakistan 8 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudingerweg 5, 55128 Mainz, Germany 9 Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, 12622 Giza, Egypt 10 Department of Chemistry, Faculty of Science, University of Kuwait, 13060 Safat, Kuwait 11 H.E.J. Research Institute of Chemistry,
  • The Transactions Session 1894-95

    The Transactions Session 1894-95

    No. 11. THE TRANSACTIONS JOURNAL OF PROCEEDINGS DUMFRIESSHIRE AND GALLOWAY Natural Hislory & Anfiquarian Sociely. FOUNDED NOVEMBER, 1862. SESSION 1894-95 PRINTED AT THE COURIER AND HERALD OFFICES, DUMFRIES. 1 896. ®l*^*^**5**8»»5*»t*»J***^5**********^5^*^^ No. 11. THE TRANSACTIONS JOURNAL OF PROCEEDINGS DUMFRIESSHIRE AND GALLOWAY Natural Hislory & Antiquarian Society. \^ ^ - "•' FOUNDED NOVEMBER, 1862. V/> ^,^^' SESSION 1894-9 5 PRINTED AT THECOT'KIKR AND HERALD OFFICES, DUMFRIES. 1896. O O XJ IT C I H.- Sir JAMES CRICHTON-BROWNE, M.D., LL.D., F.R.S. THOMAS M'KIE, F.S.A., Advocate. WILLIAM JARDINE MAXWELL, M.A., Advocate. .TAMES GIBSON HAMILTON STARKE, M.A., Advocate. PHILIP SULLEY, F.R. His. Soc. EDWARD .T. CHINNOCK, LL.D.. M.A., LL.B. S!ivea»uvev. JOHN A. MOODIE, Solicitor. Sxbvaviatf. JAMES LENNOX, F.S.A. (Lurator of Sevbatriutn. GEORGE F. SCOTT.ELLIOT, M.A., B.Sc, F.L.S., assisted by the Misses HANNAY. Curator of ^u»eunt. PETER GRAY. (Qt^ec '^exnbev9. Rev. WILLIAM ANDSON. JAMES BARBOUR, Architect. JAMES DAVIDSON, F.I.C. JAMES C. R. MACDONALD, M.A„ W.S. ROBERT MURRAY. JOHN NEILSON, M.A. GEORGE H. ROBB, M.A. JAMES MAXWELL ROSS, M.A., M.B. JAMES S. THOMSON. JAMES WATT, COnSTTEnSTTS- Pagt'. Secretary's Reixirt ... .. 1 . • 2 Treasurer's RejKirt . .. ... The Home of Annie Laurie. Rev. Sir E. Laurie . 3 Botanical Notes for 1894. J. M'Andrew 10 Kirkbean Folklore. S. Arnott . 11 Dumfrie.s Sixty Years ago. R. H. Taylor IS Antiquities of Dunscore. Rev. R. Simpson . 27 Colvend during Fifty Years. Rev. J.
  • Supplementary File 2A Revised

    Supplementary File 2A Revised

    Supplementary file 2A. Differentially expressed genes in aldosteronomas compared to all other samples, ranked according to statistical significance. Missing values were not allowed in aldosteronomas, but to a maximum of five in the other samples. Acc UGCluster Name Symbol log Fold Change P - Value Adj. P-Value B R99527 Hs.8162 Hypothetical protein MGC39372 MGC39372 2,17 6,3E-09 5,1E-05 10,2 AA398335 Hs.10414 Kelch domain containing 8A KLHDC8A 2,26 1,2E-08 5,1E-05 9,56 AA441933 Hs.519075 Leiomodin 1 (smooth muscle) LMOD1 2,33 1,3E-08 5,1E-05 9,54 AA630120 Hs.78781 Vascular endothelial growth factor B VEGFB 1,24 1,1E-07 2,9E-04 7,59 R07846 Data not found 3,71 1,2E-07 2,9E-04 7,49 W92795 Hs.434386 Hypothetical protein LOC201229 LOC201229 1,55 2,0E-07 4,0E-04 7,03 AA454564 Hs.323396 Family with sequence similarity 54, member B FAM54B 1,25 3,0E-07 5,2E-04 6,65 AA775249 Hs.513633 G protein-coupled receptor 56 GPR56 -1,63 4,3E-07 6,4E-04 6,33 AA012822 Hs.713814 Oxysterol bining protein OSBP 1,35 5,3E-07 7,1E-04 6,14 R45592 Hs.655271 Regulating synaptic membrane exocytosis 2 RIMS2 2,51 5,9E-07 7,1E-04 6,04 AA282936 Hs.240 M-phase phosphoprotein 1 MPHOSPH -1,40 8,1E-07 8,9E-04 5,74 N34945 Hs.234898 Acetyl-Coenzyme A carboxylase beta ACACB 0,87 9,7E-07 9,8E-04 5,58 R07322 Hs.464137 Acyl-Coenzyme A oxidase 1, palmitoyl ACOX1 0,82 1,3E-06 1,2E-03 5,35 R77144 Hs.488835 Transmembrane protein 120A TMEM120A 1,55 1,7E-06 1,4E-03 5,07 H68542 Hs.420009 Transcribed locus 1,07 1,7E-06 1,4E-03 5,06 AA410184 Hs.696454 PBX/knotted 1 homeobox 2 PKNOX2 1,78 2,0E-06
  • Response of Desert Biological Soil Crusts to Alterations in Precipitation Frequency

    Response of Desert Biological Soil Crusts to Alterations in Precipitation Frequency

    Oecologia (2004) 141: 306–316 DOI 10.1007/s00442-003-1438-6 PULSE EVENTS AND ARID ECOSYSTEMS Jayne Belnap . Susan L. Phillips . Mark E. Miller Response of desert biological soil crusts to alterations in precipitation frequency Received: 15 May 2003 / Accepted: 20 October 2003 / Published online: 19 December 2003 # Springer-Verlag 2003 Abstract Biological soil crusts, a community of cyano- treatment. The crusts dominated by the soil lichen bacteria, lichens, and mosses that live on the soil surface, Collema, being dark and protruding above the surface, occur in deserts throughout the world. They are a critical dried the most rapidly, followed by the dark surface component of desert ecosystems, as they are important cyanobacterial crusts (Nostoc-Scytonema-Microcoleus), contributors to soil fertility and stability. Future climate and then by the light cyanobacterial crusts (Microcoleus). scenarios predict alteration of the timing and amount of This order reflected the magnitude of the observed precipitation in desert environments. Because biological response: crusts dominated by the lichen Collema showed soil crust organisms are only metabolically active when the largest decline in quantum yield, chlorophyll a, and wet, and as soil surfaces dry quickly in deserts during late protective pigments; crusts dominated by Nostoc-Scytone- spring, summer, and early fall, the amount and timing of ma-Microcoleus showed an intermediate decline in these precipitation is likely to have significant impacts on the variables; and the crusts dominated by Microcoleus physiological functioning of these communities. Using the showed the least negative response. Most previous studies three dominant soil crust types found in the western of crust response to radiation stress have been short-term United States, we applied three levels of precipitation laboratory studies, where organisms were watered and frequency (50% below-average, average, and 50% above- kept under moderate temperatures.
  • FMB Ch05-Gerwick.Indd

    FMB Ch05-Gerwick.Indd

    PB Marine Cyanobacteria Ramaswamy et al. 175 5 The Secondary Metabolites and Biosynthetic Gene Clusters of Marine Cyanobacteria. Applications in Biotechnology Aishwarya V. Ramaswamy, Patricia M. Flatt, Daniel J. Edwards, T. Luke Simmons, Bingnan Han and William H. Gerwick* Abstract Marine cyanobacteria have proven to be one of the most versatile marine producers of secondary metabolites. Many of these metabolites demonstrate antiproliferative activity (e.g. curacin A, dolastatins), acute cytotoxic activity (e.g. apratoxin, hectochlorin) or have specific neurotoxic activity (e.g. kalkitoxin, antillatoxin), making them invaluable as potential therapeutic leads or pharmacological tools. The predominant biogenetic theme in cyanobacterial natural products chemistry is the integration of polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS) along with a variety of unusual tailoring or modifying enzymes, and accounts for the tremendous structural diversity of their metabolites. Only recently has the genetic architecture of several cyanobacterial biosynthetic gene clusters been determined, and studies to understand and exploit this biosynthentic machinery present an exciting new frontier. This chapter will summarize the properties of several notable metabolites from marine cyanobacteria that have clinical or pharmacological applications followed by a detailed account of their biosyntheses at the molecular genetic level and their potential applications in biotechnology. 1. Introduction Cyanobacteria, also known as blue-green algae, are ancient (ca. 2 x 109 years) photosynthetic prokaryotes which inhabit a wide diversity of habitats including *For correspondence email [email protected] 176 Marine Cyanobacteria Ramaswamy et al. 177 open oceans, tropical reefs, shallow water environments, terrestrial substrates, aerial environments such as in trees and rock faces, and fresh water ponds, streams and puddles (Whitton and Potts, 2000) .
  • Molecular Architectures of Benzoic Acid-Specific Type III Polyketide Synthases

    Molecular Architectures of Benzoic Acid-Specific Type III Polyketide Synthases

    research papers Molecular architectures of benzoic acid-specific type III polyketide synthases ISSN 2059-7983 Charles Stewart Jr,a,b* Kate Woods,a Greg Macias,a Andrew C. Allan,c,d Roger P. Hellensc,e and Joseph P. Noela aHoward Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA, bMacromolecular Received 11 July 2017 X-ray Crystallography Facility, Office of Biotechnology, Iowa State University, 0202 Molecular Biology Building, 2437 c Accepted 17 November 2017 Pammel Drive, Ames, IA 50011, USA, The New Zealand Institute for Plant and Food Research Limited (PFR), Auckland, New Zealand, dSchool of Biological Sciences, University of Auckland, Auckland, New Zealand, and eQueensland University of Technology, Brisbane, Queensland 4001, Australia. *Correspondence e-mail: [email protected] Edited by A. Berghuis, McGill University, Canada Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct clade of type III polyketide synthases (PKSs) that use benzoic acid- Keywords: chalcone synthase; biphenyl derived substrates to produce defense metabolites in plants. The use of benzoyl- synthase; benzophenone synthase; polyketide CoA as an endogenous substrate is unusual for type III PKSs. Moreover, synthase; thiolase; benzoyl-CoA. sequence analyses indicate that the residues responsible for the functional diversification of type III PKSs are mutated in benzoic acid-specific type III PDB references: benzophenone synthase, 5uco; chalcone synthase, 5uc5; biphenyl synthase, PKSs. In order to gain a better understanding of structure–function relationships 5w8q; biphenyl synthase, complex with within the type III PKS family, the crystal structures of biphenyl synthase from benzoyl-CoA, 5wc4 Malus  domestica and benzophenone synthase from Hypericum androsaemum were compared with the structure of an archetypal type III PKS: chalcone Supporting information: this article has synthase from Malus  domestica.