研究者データベース

研究者情報

マスター

アカウント(マスター)

  • 氏名

    URIA AGUSTINUS ROBERT(ウリア アグステイヌス ロベルト), ウリア アグステイヌス ロベルト

所属(マスター)

  • 薬学研究院 創薬科学研究教育センター

所属(マスター)

  • 薬学研究院 創薬科学研究教育センター

researchmap

プロフィール情報

プロフィール情報

  • ウリア
  • アグステイヌス ロベルト
  • ID各種

    202001010812339062

業績リスト

経歴

  • 2020年06月 - 現在 北海道大学
  • 2017年05月 - 2020年05月 北海道大学 薬学部
  • 2015年02月 - 2017年04月 Indonesian Ministry of Marine Affairs and Fisheries Research Center for Marine and Fisheries Product Processing and Biotechnology
  • 2013年02月 - 2015年01月 ETH Zurich - Swiss Federal Institute of Technology Institute of Microbiology

学歴

  • 2007年10月 - 2012年12月   The University of Bonn
  • 2002年09月 - 2004年02月   Wageningen University
  • 1994年09月 - 1999年07月   Sam Ratulangi University

論文

  • Inneke F. M. Rumengan, Vera I. Y. Roring, Jabal R. Haedar, Mayse S. Siby, Aldian H. Luntungan, Beivy J. Kolondam, Agustinus R. Uria, Toshiyuki Wakimoto
    Symbiosis 2021年04月22日 [査読有り]
  • Agustinus Robert Uria, Toshiyuki Wakimoto
    Topics in Heterocyclic Chemistry 2020年 [査読有り]
  • Agustinus R. Uria, Jörn Piel, Toshiyuki Wakimoto
    Methods in Enzymology 604 287 - 330 2018年01月01日 [査読有り][通常論文]
     
    © 2018 Elsevier Inc. Microbial symbionts are recognized as the important sources of numerous sponge-derived metabolites with potent biological activities. The limitation to cultivate the majority of potential symbionts has hampered attempts to explore and exploit their natural products for further development toward medical applications. Metagenomics-guided approaches have enabled cloning of natural product biosynthesis genes from uncultured microbial symbionts. Subsequent activation of biosynthesis genes in easily culturable bacteria could lead to the sustainable production of rare sponge-derived compounds. In this chapter, we highlight metagenomic strategies to reveal natural product biosynthetic pathways in sponge metagenomes based on the calyculin and misakinolide polyketides. Techniques to identify the compound producer are briefly discussed. We further describe examples of functional studies of the biosynthetic pathways of these two compound types with a special emphasis on the general experimental protocols for the activity assays of key proteins involved in their biosynthesis.
  • Duncan R.M. Smith, Agustinus R. Uria, Eric J.N. Helfrich, Daniela Milbredt, Karl Heinz Van Pée, Jörn Piel, Rebecca J.M. Goss
    ACS Chemical Biology 12 5 1281 - 1287 2017年05月19日 [査読有り][通常論文]
     
    © 2017 American Chemical Society. Uncultured bacteria from sponges have been demonstrated to be responsible for the generation of many potent, bioactive natural products including halogenated metabolites.1 The identification of gene clusters from the metagenomes of such bacterial communities enables the discovery of enzymes that mediate new and useful chemistries and allows insight to be gained into the biogenesis of potentially pharmacologically important natural products. Here we report a new pathway to the keramamides (krm); the first functional evidence for the existence of a distinct producer in the Theonella swinhoei WA chemotype is revealed, and a key enzyme on the pathway, a unique flavin-dependent halogenase with a broad substrate specificity, with potential as a useful new biocatalytic tool, is described.
  • Nia M. Kurnia, Agustinus R. Uria, Yudi Kusnadi, Lidia Dinawati, Dewi S. Zilda, Tri A. Hadi, Siswa Setyahadi, Feliatra Felix
    HAYATI Journal of Biosciences 24 1 6 - 15 2017年01月 [査読有り][通常論文]
     
    © 2017 Institut Pertanian Bogor There has been emerging evidence that the bacteria associated with marine sponges are the key producers of many complex bioactive compounds. The as-yet uncultured candidate bacterial genus “Candidatus Entotheonella” of the marine sponge Theonella swinhoei from Japan have recently been recognized as the source of numerous pharmacologically relevant polyketides and modified peptides, as previously reported by the Piel group (Wilson et al. 2014). This work reported the presence of “Candidatus Entotheonella sp.” in the highly complex microbiome of an Indonesian marine sponge from Kapoposang Island, South Sulawesi. We further identified the Kapoposang sponge specimen used in this work as Rhabdastrella sp. based on the integrated morphological, histological, and cytochrome oxidase subunit I (COI) gene analyses. To detect the polyketide biosynthetic machinery called type I polyketide synthase (PKS) in this Indonesian Rhabdastrella sp., we amplified and cloned the ketosynthase-encoding DNA regions of approximately 700 bp from the uncultured sponge's microbiome. Further sequencing and analysis of several randomly chosen clones indicated that all of them are mostly likely involved in the biosynthesis of methyl-branched fatty acids. However, employing a PKS-targeting primer designed in this work led to the isolation of four positive clones. BlastX search and subsequent phylogenetic analysis showed that one of the positive clones, designed as RGK32, displayed high homology with ketosynthase domains of many type I PKS systems and may belong to the subclass cis-AT PKS group.
  • A.R. Uria, D.S. Zilda
    Advances in Food and Nutrition Research (Elsevier) 78 1 - 26 2016年 [査読有り][招待有り]
     
    © 2016 Elsevier Inc. Marine microorganisms are a rich reservoir of highly diverse and unique biocatalysts that offer potential applications in food, pharmaceutical, fuel, and cosmetic industries. The fact that only less than 1% of microbes in any marine habitats can be cultured under standard laboratory conditions has hampered access to their extraordinary biocatalytic potential. Metagenomics has recently emerged as a powerful and well-established tool to investigate the vast majority of hidden uncultured microbial diversity for the discovery of novel industrially relevant enzymes from different types of environmental samples, such as seawater, marine sediment, and symbiotic microbial consortia. We discuss here in this review about approaches and methods in metagenomics that have been used and can potentially be used to mine commercially useful biocatalysts from uncultured marine microbes.
  • Agustinus R. Uria
    Squalen Bulletin of Marine and Fisheries Postharvest and Biotechnology 2015年10月13日 [査読有り][通常論文]
     
    Symbiotic bacteria associated with marine sponges have frequently been proposed as the true producer of many bioactive natural products with potent anticancer activities. However, the majority of these complex symbiotic bacteria cannot be cultivated under laboratory conditions, hampering efforts to access and develop their potent compounds for therapeutic applications. Metagenome mining is a powerful cultivation-independent tool that can be used to search for new natural product biosynthetic pathways from highly complex bacterial consortia. Some notable examples of natural products, in which their biosynthetic pathways have been cloned by metagenome mining are onnamide A, psymberin, polytheonamides, calyculin, and misakinolide A. Subsequent expression of the pathways in easily culturable bacteria, such as Escherichia coli, could lead to the sustainable production of rare promising natural products. This review discusses principles of metagenome mining developed to gain access to natural product biosynthetic pathways from uncultured symbiotic bacteria of marine sponges. This includes detecting biosynthetic genes in sponge metagenome, creating large metagenomic library, rapid screening of metagenomic library, and clone sequencing. For many natural products made by modular polyketide synthases (PKSs) and hybrids with non-ribosomal peptide synthetases (NRPSs), their biosynthetic pathways as well as structures of final products can be predicted with high accuracy through bioinformatic analysis and sometimes combined with functional proof. Further metagenome sequencing integrated with single-cell analysis and chemical studies could provide insights into the remarkable biosynthetic capacity of uncultivated bacterial symbionts, thereby facilitating the discovery and sustainable production of a wide diversity of sponge-derived complex compounds.
  • Reiko Ueoka, Agustinus R. Uria, Silke Reiter, Tetsushi Mori, Petra Karbaum, Eike E. Peters, Eric J.N. Helfrich, Brandon I. Morinaka, Muriel Gugger, Haruko Takeyama, Shigeki Matsunaga, Jörn Piel
    Nature Chemical Biology 11 9 705 - 712 2015年09月20日 [査読有り][通常論文]
     
    Actin-targeting macrolides comprise a large, structurally diverse group of cytotoxins isolated from remarkably dissimilar micro- and macroorganisms. In spite of their disparate origins and structures, many of these compounds bind actin at the same site and exhibit structural relationships reminiscent of modular, combinatorial drug libraries. Here we investigate biosynthesis and evolution of three compound groups: misakinolides, scytophycin-type compounds and luminaolides. For misakinolides from the sponge Theonella swinhoei WA, our data suggest production by an uncultivated 'Entotheonella' symbiont, further supporting the relevance of these bacteria as sources of bioactive polyketides and peptides in sponges. Insights into misakinolide biosynthesis permitted targeted genome mining for other members, providing a cyanobacterial luminaolide producer as the first cultivated source for this dimeric compound family. The data indicate that this polyketide family is bacteria-derived and that the unusual macrolide diversity is the result of combinatorial pathway modularity for some compounds and of convergent evolution for others.
  • Micheal C. Wilson, Tetsushi Mori, Christian Rückert, Agustinus R. Uria, Maximilian J. Helf, Kentaro Takada, Christine Gernert, Ursula A.E. Steffens, Nina Heycke, Susanne Schmitt, Christian Rinke, Eric J.N. Helfrich, Alexander O. Brachmann, Cristian Gurgui, Toshiyuki Wakimoto, Matthias Kracht, Max Crüsemann, Ute Hentschel, Ikuro Abe, Shigeki Matsunaga, Jörn Kalinowski, Haruko Takeyama, Jörn Piel
    Nature 506 7486 58 - 62 2014年 [査読有り][通常論文]
     
    Cultivated bacteria such as actinomycetes are a highly useful source of biomedically important natural products. However, such 'talented' producers represent only a minute fraction of the entire, mostly uncultivated, prokaryotic diversity. The uncultured majority is generally perceived as a large, untapped resource of new drug candidates, but so far it is unknown whether taxa containing talented bacteria indeed exist. Here we report the single-cell-and metagenomics-based discovery of such producers. Two phylotypes of the candidate genus 'Entotheonella' with genomes of greater than 9 megabases and multiple, distinct biosynthetic gene clusters co-inhabit the chemically and microbially rich marine sponge Theonella swinhoei. Almost all bioactive polyketides and peptides known from this animal were attributed to a single phylotype. 'Entotheonella' spp. are widely distributed in sponges and belong to an environmental taxon proposed here as candidate phylum 'Tectomicrobia'. The pronounced bioactivities and chemical uniqueness of 'Entotheonella' compounds provide significant opportunities for ecological studies and drug discovery. © 2014 Macmillan Publishers Limited. All rights reserved.
  • Micheal C. Wilson, Tetsushi Mori, Christian Rückert, Agustinus R. Uria, Maximilian J. Helf, Kentaro Takada, Christine Gernert, Ursula A.E. Steffens, Nina Heycke, Susanne Schmitt, Christian Rinke, Eric J.N. Helfrich, Alexander O. Brachmann, Cristian Gurgui, Toshiyuki Wakimoto, Matthias Kracht, Max Crüsemann, Ute Hentschel, Ikuro Abe, Shigeki Matsunaga, Jörn Kalinowski, Haruko Takeyama, Jörn Piel
    Nature 507 7491 262  2014年 [査読有り][通常論文]
  • Investigating natural product biosynthesis in uncultivated symbiotic bacteria of the marine sponge Theonella swinhoei.
    Uria A.R
    Doctoral Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn (Advisor: Joern Piel) 2013年
  • Michael F. Freeman, Cristian Gurgui, Maximilian J. Helf, Brandon I. Morinaka, Agustinus R. Uria, Neil J. Oldham, Hans Georg Sahl, Shigeki Matsunaga, Jörn Piel
    Science 338 6105 387 - 390 2012年10月19日 [査読有り][通常論文]
     
    It is held as a paradigm that ribosomally synthesized peptides and proteins contain only L-amino acids. We demonstrate a ribosomal origin of the marine sponge - derived polytheonamides, exceptionally potent, giant natural-product toxins. Isolation of the biosynthetic genes from the sponge metagenome revealed a bacterial gene architecture. Only six candidate enzymes were identified for 48 posttranslational modifications, including 18 epimerizations and 17 methylations of nonactivated carbon centers. Three enzymes were functionally validated, which showed that a radical S-adenosylmethionine enzyme is responsible for the unidirectional epimerization of multiple and different amino acids. Collectively, these complex alterations create toxins that function as unimolecular minimalistic ion channels with near-femtomolar activity. This study broadens the biosynthetic scope of ribosomal systems and creates new opportunities for peptide and protein bioengineering.
  • Agustinus Uria, Jörn Piel
    Phytochemistry Reviews 8 2 401 - 414 2009年06月 [査読有り][通常論文]
     
    Sessile marine animals like sponges, tunicates, and bryozoans are a rich source of bioactive natural products, many of which exhibit potent anticancer activities. However, most of these substances are available in very limited amounts only, which has prohibited further drug development. Recent evidence suggests that symbiotic bacteria might be the true producers of many animal-derived metabolites. In addition to revealing fascinating perspectives for research in marine chemical ecology, these findings suggest new solutions to the supply problem. Although most symbionts remain uncultivated, bacterial production systems might be created by isolating biosynthetic genes from marine metagenomes, and expressing them in culturable bacterial hosts. This review discusses cell-sorting, natural product visualization, and phylogenetic approaches to identify symbiotic producers. In addition, strategies to isolate genes and gene clusters from marine species consortia are described. These techniques have provided insights into the bacterial origin and biosynthesis of polyketides like the onnamides, swinholides, and bryostatins, of peptides including the patellamides, chlorinated dipeptides, and theopalauamide as well as of brominated biphenylethers. © 2009 Springer Science+Business Media B.V.
  • Ronnie Machielsen, Agustinus R. Uria, Servé W.M. Kengen, John Van Der Oost
    Applied and Environmental Microbiology 72 1 233 - 238 2006年01月 [査読有り][通常論文]
     
    The gene encoding a novel alcohol dehydrogenase that belongs to the aldo-keto reductase superfamily has been identified in the hyperthermophilic archaeon Pyrococcus furiosus. The gene, referred to as adhD, was functionally expressed in Escherichia coli and subsequently purified to homogeneity. The enzyme has a monomeric conformation with a molecular mass of 32 kDa. The catalytic activity of the enzyme increases up to 100°C, and a half-life value of 130 min at this temperature indicates its high thermostability. AdhD exhibits a broad substrate specificity with, in general, a preference for the reduction of ketones (pH optimum, 6.1) and the oxidation of secondary alcohols (pH optimum, 8.8). Maximal specific activities were detected with 2,3-butanediol (108.3 U/mg) and diacetyl-acetoin (22.5 U/mg) in the oxidative and reductive reactions, respectively. Gas chromatrography analysis indicated that AdhD produced mainly (S)-2-pentanol (enantiomeric excess, 89%) when 2-pentanone was used as substrate. The physiological role of AdhD is discussed. Copyright © 2006, American Society for Microbiology. All Rights Reserved.

MISC

  • EL Ginting, K Kemer, S Wullur, AR Uria Geomicrobiology Journal 37 (1) 50 -58 2020年01月02日 [査読有り]
  • DS Zilda, YN Fawzya, AR Uria Squalen Bulletin of Marine and Fisheries Postharvest and Biotechnology 13 (3) 101 -101 2018年12月30日 [査読有り]
     
    Proteases or peptidases is known as a largest group of hydrolytic enzymes and have been applied in various industries such as food, pharmacy, leather, detergent and waste treatment. Although they are also produced by plants and animals, microbes remain the main source of proteases in the world market which mostly derived from Bacillus sp. Aims of this research were to identify isolate BII-1 and study its protease. Analysis of 16Sr RNA sequencing showed the identity of BII-1 as Bacillus subtilis (99% similarity with the same species in GenBank). It was found that protease from BII-1 exhibited optimal temperature and pH of 50 oC and 8-9, respectively. It was activated by Li2+, Na2+, Mg2+ and K+. The degenerated primer for protease gene was designed, and a partial protease gene was amplified from BII-1. The sequencing result showed that this amplified gene shared 100 and 99% similarity with those from Geobacillus thermophiles and Bacillus subtilis in the GenBank, respectively.Keywords: protease, bacteria, Bacillus subtilis, Geobacillus thermophylus
  • S Seprianto, DS Zilda, YN Fawzya, S Suharsono, P Lisdiyanti, AR Uria Squalen Bulletin of Marine and Fisheries Postharvest and Biotechnology 11 (1) 31 -31 2016年05月19日 [査読有り]
     
    Microbial Transglutaminase (MTGase, EC 2.3.2.13) is an enzyme that catalyzes the transfer of acyl group. Many microbial strains that produce MTGase belong to Streptomyces members. This research was aimed at cloning of a MTGase gene. PCR–based screening of ten MTGase-producing streptomyces isolates from soil in West Nusa Tenggara led to detection of one potential isolate, designated as TTA 02 SDS 14. The partial  MTGase-encoding gene (470 bp)  was amplified by PCR and sequenced. The sequence result indicate its similarity of 93 % with that of Streptomyces cinnamoneus. The 16S rRNA gene analysis showed its identity as Streptomyces thioleteus. Fosmid-based construction of a genomic library from the isolate  and subsequent screening led to the isolation of  a ~40-Kb fosmid harboring a MTGase gene.
  • Marine Natural Products: prospects and impacts on the sustainable development in Indonesia
    Dewi A.S, Tarman K, Uria A.R Conf. paper in the Proceedings ISSM - Indonesian student scientific meeting on sustainable development in Indonesia: An interdisciplinary approach (May 13-15, 2008 at Delft University of Technology) 2008年05月 [査読有り]
  • Alcohol dehydrogenases from marine hyperthermophilic microorganisms and their importance to the pharmaceutical industry
    Uria A.R, Machielsen R, Dutilh B.E, Huynen M.A, van der Oost J Conf. paper in the Proceedings International seminar and workshop on marine biodiversity & their potential for developing bio-pharmaceutical industry in Indonesia (May 17-18, 2006 in Jakarta) 2006年05月 [査読有り][通常論文]
  • Properties of chitinase from a bacterial strain associated with marine sponge
    Uria A.R, Chasanah E Conf. paper in the Proceedings ASEAN Biochemistry seminar and workshop on enzymes: industrial and medical prospects (February 6-7, 2006 at Airlangga University, Surabaya) 2006年02月 [査読有り][通常論文]

講演・口頭発表等

  • Understanding natural product biosynthesis in uncultivated marine bacteria towards the development of sustainable production systems  [招待講演]
    Webinar Nasional Kefarmasian (Pharmacy National Webinar) organized by Malahayati University 2020年11月 口頭発表(基調)
  • When metagenomics meets synthetic biology: new opportunities and potential applications in the digital era.  [招待講演]
    Uria, A.R.
    International Webinar of Mathematics, Natural Sciences, and Learning in the New Normal Order - IWMANSELEN 2020 2020年10月 口頭発表(基調)
  • Biosynthetic potential of rare marine bacteria isolated from Okinawan sponges  [通常講演]
    Uria A.R, Haedar J.R, Jomori T, Matsuda K, Wakimoto T
    The 12th Marine Biotechnology Conference held in Shizuoka 2019年09月 ポスター発表
  • Investigating spongistatin biosynthesis in complex sponge-bacteria association  [招待講演]
    Uria, A.R, Matsuda K, Wakimoto, T
    The 3rd International Symposium on Sponge Microbiology (ISSM), Shanghai (China) 2018年10月
  • Investigating natural product biosynthesis in complex marine sponge-bacteria association  [招待講演]
    Uria A.R, Matsuda K, Wakimoto T
    Young Researchers Symposium on Redesigning Biosynthetic Machineries, Otaki (Japan) 2018年05月 口頭発表(招待・特別)
  • Investigating natural product biosynthetic pathways in highly complex symbiotic bacterial assemblages of marine sponges  [招待講演]
    The 2nd International Microbial Biotechnology (IMBC2) at Atma Jaya Catholic University of Indonesia, Jakarta, November 15-16, 2016 2016年10月 口頭発表(基調)
  • Investigating the biosynthetic pathways of defensive compounds in uncultured microbiome of marine sponges  [招待講演]
    The 6th Indonesian Biotechnology Conference (IBC IV): “Enhancing industrial competitiveness through biotechnology innovation”, in Solo, Surakarta, September 6-8, 2016, organized by Indonesian Biotechnology Consortium. 2016年09月 口頭発表(招待・特別)
  • Phylogeny-guided identification of type I polyketide synthase in uncultured microbiome of a marine sponge from Kapoposang Island  [通常講演]
    N.M. Kurnia, Y. Kusnadi, L. Dinawati, D.S. Zilda, Tri A. Hadi, S. Setyahadi, F. Felix, A.R. Uria
    ASEAN Microbial Biotechnology Conference held in Bali on August 3-4, 2016 2016年07月 口頭発表(一般)
  • Revealing the biosynthetic capacity of uncultured symbiotic bacteria
    A.R. Uria, C. Ruckert, J. Kalinowksi, S. Matsunaga, J. Piel
    International VAAM Workshop on Sept. 28-30, 2011 in Bonn, Germany 2011年09月 ポスター発表
  • Analyzing the drug potential of uncultivated symbionts of the sponge Theonella swinhoei
    BMBF GenBioCom cluster-meeting in Freudenstadt-Lauterbad, Schwarzwald, Germany, on October 21-22, 2010. 2010年10月 口頭発表(招待・特別)
  • Biosynthesis of the antitumor polyketide misakinolide A by an uncultivated symbiont of the marine sponge Theonella swinhoei
    A.R. Uria, S. Matsunaga, J. Piel
    VAAM symposium on symbiotic interaction, on October 7-8, 2010 at Wurzburg University, Germany 2010年10月 ポスター発表
  • Insights into the secondary metabolism of an unusual uncultured symbiont of marine sponges  [招待講演]
    Die 39. Doktorandenworkshop, Naturstoffe: Chemie, Biologie und Okologie in Jena, Germany, April 16, 2010 2010年04月 口頭発表(一般)
  • Insight into the secondary metabolism of Entotheonella sp., an uncultivated symbiont of marine sponges
    A.R. Uria, S. Matsunaga, and J. Piel
    Die 22. Irseer Naturstofftage, Aktuelle Entwicklungen in der Naturstoff-Forschung, February 22-24, 2010 in Irsee, Germany 2010年02月 ポスター発表

担当経験のある科目(授業)

  • 天然物化学北海道大学

所属学協会

  • SBJ - The Society for Biotechnology, Japan   AFOB - Asian Federation of Biotechnology   FEMS - Federation of European Microbiological Societies   IMBA - International Marine Biotechnology Association   

共同研究・競争的資金等の研究課題

  • Investigating natural product biosynthetic pathways in the microbiomes associated with long-lived aquatic vertebrates
    日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2021年07月 -2024年03月
  • Biosynthetic studies of secondary metabolites derived from microbiomes of marine sponges

産業財産権

  • US Patent US20140234903A1:Biosynthetic gene cluster for the production of peptid/protein analogues  2014年
    Piel, J, Gurgui, C, Freeman, M.F, Uria, A.R, Helf, M.J  ETH Zurich

社会貢献活動

  • What inspired me to pursue a career in science?
    期間 : 2018年07月09日
    役割 : 講師
    主催者・発行元 : Japan Society for the Promotion of Science (JSPS), and Akebi Secondary School in Noboribetsu, Hokkaido
    イベント・番組・新聞雑誌名 : Science Dialogue Program


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