Skip to Main Content

INFORMATION FOR

Scott Strobel, PhD

Provost and Henry Ford II Professor of Molecular Biophysics and Biochemistry and Professor of Chemistry; Howard Hughes Medical Institute Professor

Contact Information

Scott Strobel, PhD

Research Summary

Our research explores 1) hydrocarbon production by novel fungi as alternative fuel source and 2) RNA biochemistry. The first area focuses on endophytic fungus isolated from Northern Patagonia that produces and excretes a broad spectrum of fuel related hydrocarbons. The second area employs biochemistry and structural biology to study the ribosome reaction mechanism, RNA catalysis, and RNA small molecule interactions that regulate riboswitches.

Specialized Terms: Antibiotics; Nucleic Acid Bioorganic Chemistry; Ribosome; Ribozyme; RNA Catalysis; RNA-Protein Interaction; Translation; Riboswitches, Biofuels; Endophytes; Natural Product Discovery

Extensive Research Description

Research in the Strobel laboratory focuses on RNA catalysis and biofuel production.

Direct Conversion of Cellulose to Biofuel by a novel fungus.

This is the newest project in the lab and a new research direction for our group closely related to the undergraduate Rainforest Expedition program supported by HHMI. This project involves an emerging biotechnology for the production of hydrocarbons from cellulose-based waste feedstock with a low-carbon footprint that is chemically equivalent to jet fuel. Gliocladium roseum (NRRL 50072) is an endophytic fungus recently isolated from Northern Patagonia that produces and excretes a broad spectrum of straight and branched medium chain-length hydrocarbons, including heptane, octane, undecane, dodecane and hexadecane, when grown in an sealed vessel. G. roseum can also generate and release these products when grown on cellulose, the world's most abundant natural organic compound. This organism has the potential to produce desirable biofuels via a fermentation process that is nearly carbon neutral. It is a basic science observation with clear implications for energy production and utilization.

The goals of this project are to characterize the biosynthetic basis of hydrocarbon production and release by G. roseum, to isolate the enzymes responsible for hydrocarbon synthesis and transport, and to use this information to optimize the yields of biofuel output. Overproduction will be achieved either by biological engineering of keys genes in the pathway, or transfer of the biosynthetic pathway to organisms used in standard fermentation processes. The hydrocarbon products and their derivatives will be subjected to chemical analysis and combustion studies. Realization of these goals will transform this basic science observation into real world applications that could transform the source and long-term availability of petroleum fuels.

We also have several ongoing projects in the area of RNA biochemistry.

Protein Synthesis.

Crystallographic studies reveal that the ribosomal peptidyl transferase center is composed exclusively of rRNA, i.e., that the ribosome is a ribozyme. We aim to determine how this biologically fundamental reaction is catalyzed. We are taking several approaches to understand this enzyme, including: (i) synthesis and characterization of transition state inhibitors; (ii) preparation of modified A-site and P-site tRNA substrates to test for substrate assisted catalysis of peptide bond formation by enzyme kinetic analysis; (iii) purification of mutant ribosomes to assess the role of rRNA functional groups; (iv) investigating the reaction transition state by kinetic isotope effect analysis and by determining the Brønsted coefficient for the ester aminolysis reaction.

Intron Splicing.

The discovery of the RNA self-splicing group I intron provided the first demonstration that not all enzymes are proteins. We recently reported the X-ray crystal structure of a catalytically active group I intron splicing intermediate. This is the first splicing complex of any kind to include a complete intron, both exons and an organized active site occupied with metal ions. The exon ligation is chemically equivalent for pre-mRNA splicing by the spliceosome. As a result, the chemical themes of splice site selection, exon alignment, and catalytic metal ion positioning, which are manifest in this splicing intermediate complex, are likely to find parallels in pre-mRNA splicing. We are now undertaking several additional structural and biochemical studies to characterize the entire RNA splicing pathway. The overriding goals of these studies are to: (i) understand the mechanism of RNA splicing, (ii) explain how RNA tertiary structure is formed and active sites created in the absence of proteins, (iii) reveal how metal ions contribute to RNA catalysis, and (iv) visualize the nature of the transition state of the phosphoryl transfer reaction promoted during exon ligation.

Coauthors

Research Interests

Biochemistry; Biophysics; Chemistry; Ribosomes; Biofuels; Endophytes; Chemicals and Drugs; Technology, Industry, Agriculture

Selected Publications

  • Biatriospora (Ascomycota: Pleosporales) is an ecologically diverse genus including facultative marine fungi and endophytes with biotechnological potentialKolařík M, Spakowicz D, Gazis R, Shaw J, Kubátová A, Nováková A, Chudíčková M, Forcina G, Kang K, Kelnarová I, Skaltsas D, Portero C, Strobel S, Narváez-Trujillo A. Biatriospora (Ascomycota: Pleosporales) is an ecologically diverse genus including facultative marine fungi and endophytes with biotechnological potential Plant Systematics And Evolution 2016, 303: 35-50. DOI: 10.1007/s00606-016-1350-2.
  • Stelliosphaerols A and B, sesquiterpene-polyol conjugates from an Ecuadorian fungal endophyteForcina G, Castro A, Bokesch H, Kucera K, McMahon J, Gustafson K, Strobel S. Stelliosphaerols A and B, sesquiterpene-polyol conjugates from an Ecuadorian fungal endophyte Planta Medica 2015, 81 DOI: 10.1055/s-0035-1556389.
  • Corrigendum to “Xyolide, a bioactive nonenolide from an Amazonian endophytic fungus, Xylaria feejeensis” [Tetrahedron Lett. 54 (2013) 4058–4060]Baraban E, Morin J, Phillips G, Phillips A, Strobel S, Handelsman J. Corrigendum to “Xyolide, a bioactive nonenolide from an Amazonian endophytic fungus, Xylaria feejeensis” [Tetrahedron Lett. 54 (2013) 4058–4060] Tetrahedron Letters 2014, 55: 3126. DOI: 10.1016/j.tetlet.2014.04.012.
  • ChemInform Abstract: The Bacterial Second Messenger C‐di‐GMP: Probing Interactions with Protein and RNA Binding Partners Using Cyclic Dinucleotide Analogues.Shanahan C, Strobel S. ChemInform Abstract: The Bacterial Second Messenger C‐di‐GMP: Probing Interactions with Protein and RNA Binding Partners Using Cyclic Dinucleotide Analogues. ChemInform 2013, 44: no-no. DOI: 10.1002/chin.201317261.
  • Endophyte Strain NRRL 50072 producing volatile organics is a species of AscocoryneStrobel G, Tomsheck A, Geary B, Spakowicz D, Strobel S, Mattner S, Mann R. Endophyte Strain NRRL 50072 producing volatile organics is a species of Ascocoryne Mycology: An International Journal On Fungal Biology 2010, 1: 187-194. DOI: 10.1080/21501203.2010.510122.
  • ChemInform Abstract: The Synthesis of RNA Containing the Modified Nucleotides N2‐Methylguanosine and N6,N6‐Dimethyladenosine.Rife J, Cheng C, Moore P, Strobel S. ChemInform Abstract: The Synthesis of RNA Containing the Modified Nucleotides N2‐Methylguanosine and N6,N6‐Dimethyladenosine. ChemInform 2010, 30: no-no. DOI: 10.1002/chin.199916227.
  • Aurosphaeria, a novel coelomycetous genusLee S, Strobel G, Eisenman K, Geary B, Vargas P, Strobel S. Aurosphaeria, a novel coelomycetous genus Mycotaxon 2009, 107: 463-472. DOI: 10.5248/107.463.
  • 89: Fungal endophytes as a platform for discovery of novel therapeutic strategies to inhibit pathogenic processes relevant for preterm birthLee S, Strobel S, Eisenman K, Dulay A, Boulanger L, Zhao G, Strobel G, Incarvito C, Buhimschi C, Buhimschi I. 89: Fungal endophytes as a platform for discovery of novel therapeutic strategies to inhibit pathogenic processes relevant for preterm birth American Journal Of Obstetrics And Gynecology 2008, 199: s39. DOI: 10.1016/j.ajog.2008.09.116.
  • ChemInform Abstract: Catalytic Strategies of Self‐Cleaving RibozymesCochrane J, Strobel S. ChemInform Abstract: Catalytic Strategies of Self‐Cleaving Ribozymes ChemInform 2008, 39: no-no. DOI: 10.1002/chin.200848274.
  • Present at the Flood: A First Person Guided Tour through the Early Literature in Structural Biology Richard E.DickersonPresent at the Flood: How Structural Molecular Biology Came About2006Sinauer Associates, Inc.Sunderland, MA307 pp. $34.95Strobel S. Present at the Flood: A First Person Guided Tour through the Early Literature in Structural Biology Richard E.DickersonPresent at the Flood: How Structural Molecular Biology Came About2006Sinauer Associates, Inc.Sunderland, MA307 pp. $34.95 Structure 2006, 14: 809-810. DOI: 10.1016/j.str.2006.05.004.
  • Biopolymers Exploring biological function through chemical manipulation of biopolymersStrobel S, Muir T. Biopolymers Exploring biological function through chemical manipulation of biopolymers Current Opinion In Chemical Biology 2005, 9: 545-547. DOI: 10.1016/j.cbpa.2005.10.017.
  • Synthesis of isotopically labeled puromycin derivatives for kinetic isotope effect analysis of ribosome catalyzed peptide bond formationOkuda K, Seila A, Strobel S. Synthesis of isotopically labeled puromycin derivatives for kinetic isotope effect analysis of ribosome catalyzed peptide bond formation Tetrahedron 2004, 60: 12101-12112. DOI: 10.1016/j.tet.2004.10.023.
  • Crystal structure of an intact group I self-splicing intron in complex with both intronsAdams P, Stahley M, Kosek A, Wang J, Strobel S. Crystal structure of an intact group I self-splicing intron in complex with both introns Acta Crystallographica Section A: Foundations And Advances 2004, 60: s144-s144. DOI: 10.1107/s0108767304097168.
  • ERRATUMMUTH G, CHEN L, KOSEK A, STROBEL S. ERRATUM RNA 2002, 8: 261-261. DOI: 10.1017/s1355838202019994.
  • Self‐Splicing IntronsStrobel S. Self‐Splicing Introns 2002 DOI: 10.1002/047120918x.emb1395.
  • 11 Ribozyme EnzymologyStrauss-Soukup J, Strobel S. 11 Ribozyme Enzymology 2001, 187-206. DOI: 10.1016/b978-008043408-7/50032-0.
  • Biochemical Detection of Cytidine Protonation within RNAOyelere A, Strobel S. Biochemical Detection of Cytidine Protonation within RNA Journal Of The American Chemical Society 2000, 122: 10259-10267. DOI: 10.1021/ja001918t.
  • Direct Detection of Monovalent Metal Ion Binding to a DNA G-quartet by 205Tl NMRBasu S, Szewczak A, Cocco M, Strobel S. Direct Detection of Monovalent Metal Ion Binding to a DNA G-quartet by 205Tl NMR Journal Of The American Chemical Society 2000, 122: 3240-3241. DOI: 10.1021/ja993614g.
  • 6.10 Ribozyme EnzymologyStrauss-Soukup J, Strobel S. 6.10 Ribozyme Enzymology 1999, 149-168. DOI: 10.1016/b978-0-08-091283-7.00164-8.
  • The Synthesis of RNA Containing the Modified Nucleotides N 2-Methylguanosine and N 6, N 6-DimethyladenosineRife J, Cheng C, Moore P, Strobel S. The Synthesis of RNA Containing the Modified Nucleotides N 2-Methylguanosine and N 6, N 6-Dimethyladenosine Nucleosides Nucleotides & Nucleic Acids 1998, 17: 2281-2288. DOI: 10.1080/07328319808004317.
  • The structure and biological activity of cercosporamide from Cercosporidium henningsiiSugawara F, Strobel S, Strobel G, Larsen R, Berglund D, Gray G, Takahashi N, Coval S, Stout T, Clardy J. The structure and biological activity of cercosporamide from Cercosporidium henningsii The Journal Of Organic Chemistry 1991, 56: 909-910. DOI: 10.1021/jo00003a002.
  • New anti-inflammatory pseudopterosins from the marine octocoral Pseudopterogorgia elisabethaeRoussis V, Wu Z, Fenical W, Strobel S, Van Duyne G, Clardy J. New anti-inflammatory pseudopterosins from the marine octocoral Pseudopterogorgia elisabethae The Journal Of Organic Chemistry 1990, 55: 4916-4922. DOI: 10.1021/jo00303a030.
  • Palmosalides A-C, new sesquiterpenoids from the indian ocean telestacean octocoral Coelogorgia palmosaWiemer D, Wolfe L, Fenical W, Strobel S, Clardy J. Palmosalides A-C, new sesquiterpenoids from the indian ocean telestacean octocoral Coelogorgia palmosa Tetrahedron Letters 1990, 31: 1973-1976. DOI: 10.1016/s0040-4039(00)88892-9.
  • ChemInform Abstract: Triticones A and B, Novel Phytotoxins from the Plant Pathogenic Fungus Drechslera tritici‐repentisSUGAWARA F, TAKAHASHI N, STROBEL G, STROBEL S, LU H, CLARDY J. ChemInform Abstract: Triticones A and B, Novel Phytotoxins from the Plant Pathogenic Fungus Drechslera tritici‐repentis ChemInform 1988, 19: no-no. DOI: 10.1002/chin.198839319.
  • Triticones A and B, novel phytotoxins from the plant pathogenic fungus Drechslera tritici-repentisSugawara F, Takahashi N, Strobel G, Strobel S, Lu H, Clardy J. Triticones A and B, novel phytotoxins from the plant pathogenic fungus Drechslera tritici-repentis Journal Of The American Chemical Society 1988, 110: 4086-4087. DOI: 10.1021/ja00220a085.
  • PC69 UNUSUAL SPIROCYCLIC γ-LACTAMS, TRITICONES A AND B, NOVEL PHYTOTOXINS FROM THE PLANT PATHOGENIC FUNGI DRECHSLERA TRITICIREPENTIS AND D. CATENARIUMSugawara F, Samsoedin R, Takahashi N, Strobel G, Strobel S, Liu H, Clardy J. PC69 UNUSUAL SPIROCYCLIC γ-LACTAMS, TRITICONES A AND B, NOVEL PHYTOTOXINS FROM THE PLANT PATHOGENIC FUNGI DRECHSLERA TRITICIREPENTIS AND D. CATENARIUM 1988, 525. DOI: 10.24496/intnaturalprod.1988.0_525.
  • Flow cytometry as a method for assaying the biological activity of phytotoxinsBerglund D, Strobel S, Sugawara F, Strobel G. Flow cytometry as a method for assaying the biological activity of phytotoxins Plant Science 1988, 56: 183-188. DOI: 10.1016/0168-9452(88)90033-7.
  • Bissetone, a unique antimicrobial pyranone from the gorgonian Briareu polyanthesCardellina J, Hendrickson R, Manfredi K, Strobel S, Clardy J. Bissetone, a unique antimicrobial pyranone from the gorgonian Briareu polyanthes Tetrahedron Letters 1987, 28: 727-730. DOI: 10.1016/s0040-4039(01)80973-4.