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Donald Stierle

Research Professor

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Personal Summary

After completing a B.S. in Chemistry at Southern Methodist University, Don Stierle earned a PhD in Chemistry at the University of California at Riverside. Following a two year postdoctoral appointment at Scripps Institution of Oceanography, Don took a position at Montana Tech of the University of Montana as the Organic Chemistry/Biochemistry Professor. Don was a tenured, full professor and in 2000 was unanimously granted Montana Tech’s first endowed chair in Mathematics and the Sciences, the Rose and Anna Busch Professorship, an honor he held until his departure from Tech in 2009. After 29 years of teaching and research at Montana Tech, Don joined the Department of Biomedical and Pharmaceutical Sciences at UM-Missoula as a Research Professor.

Research Interests

The Stierle Research Lab is dedicated to the isolation and structural characterization of compounds with potent, selected biological activity from both macro- and microorganisms.  These include both traditional medicinal plants and microbes isolated from unusual ecological niches. We are currently studying two very different populations of microbes: those isolated from an acid mine waste lake in Butte, Montana, and those isolated from the human microbiome. We are also studying the bioactive components of Ayurvedic plants, and the biotransformation of those components by human gut microbes.  Whatever the organism, plant or microbe or a combination of the two, it is extracted in organic solvents and a series of bioassays are used to determine the potential biological activities of these extracts. Signal transduction enzyme inhibition assays have been developed to target activity against specific disease conditions. Of particular interest are those diseases with a connection to chronic inflammation. These include many cancers, Alzheimer’s disease and autoimmune disorders. Using enzyme inhibition as a fractionation guide, we have isolated and elucidated several novel molecules that have shown potent, selective activity against specific cancers – ovarian, non-small lung and leukemia -- in the NIH 60 human cell-line assay.

We are also interested in targeting the antibiotic potential of these metabolites. We use a series of standard disk assays to guide the isolation of compounds with antifungal and antibacterial activity. The rising incidence of immunocompromised individuals has generated an array of emerging infectious diseases in critical need of prophylaxis. Of particular interest are those compounds with antifungal activity, as opportunistic mycoses are a growing problem in immunocompromised individuals, including AIDS patients and patients on immunosuppressive therapy. We are also collaborating with Dr. Allen Harmsen at Montana State University in the search for compounds with specific activity against Pneumocystis jirnoveci (formerly carinii). This unusual microbe was formerly classified as a protozoan but is now classified as a fungus. It is the causative agent of Pneumocystis carinii pneumonia, an insidious opportunistic infection in immunocompromised patients.

The Stierle lab is also looking at the potential of the Berkeley Pit Lake microbes to participate in the remediation of this 40 billion gallon acid mine waste lake that graces the northeast corner of Butte, Montana. These efforts have led to the isolation of an unusual yeast that sorbs metals even at pH 2.3.

The Stierle lab has long studied endosymbiotic microbes isolated from marine sponges and the inner bark of trees – notably the Northwest Pacific yew tree. The Stierles found that many compounds reported from sponge extracts might actually have been produced by their microbial symbionts. This work led to the discovery of a unique compound from a Bermudian sponge endosymbioticbacterium that showed activity against both pathogenic bacteria and the AIDS virus. The Stierles will work with collaborators at UM to determine how this compound affects the AIDS virus.

In the early 90’s The Stierles also searched for a fungal source of the drug taxol (paclitaxel), an anticancer agent which showed promise in clinical trials against refractory breast and ovarian cancers. Unfortunately the source organism of taxol, the northwest Pacific yew tree, had been clear-cut to the point of endangerment and could not supply the growing demands for taxol. It was clear that additional sources of taxol were necessary. Andrea isolated over 300 fungi from the inner bark and needles of yew trees in Montana, Washington, Idaho and Oregon. In 1993, the team published a report of a fungus isolated from the bark of the Pacific yew tree, Taxus brevifolia Nutt, which could produce taxol in de novo fashion. This unique fungus – Taxomyces andreanae - was named after Andrea, its discoverer. The Stierles hope to compare the production of taxol by the tree and the fungus.

Selected Publications

Selected Publications – last ten years

A Stierle, D  Stierle  2016  Secondary Metabolites of Acid Mine Waste Fungi. In "Topics in Biodiversity and Conservation", D Hawksworth, RRM Patterson (Eds), Springer, in press

Azaphilones from an Acid Mine Extremophile Strain of a Pleurostomophora sp  Stierle AA, Stierle DB, Girtsman T, Mou TC, Antczak C, Djaballah H.  J Nat Prod. 2015 Dec 24;78(12):2917-23

Bioactive Secondary Metabolites Produced by the Fungal Endophytes of Conifers. Stierle AA, Stierle DB.  Nat Prod Commun. 2015 Oct;10(10):1671-82.

Crystal structure and absolute configuration of preaustinoid A1 Stierle A, Stierle D, Decato D. . Acta Crystallogr E Crystallogr Commun. 2015 Jul 22;71(Pt 8):o596-7. Free full text Related citations

Redetermination and absolute configuration of berkeleydione  Stierle A, Stierle D, Decato D. Acta Crystallogr E Crystallogr Commun. 2015 Mar 21;71(Pt 4):o248. Free full text Related citations

Bioactive secondary metabolites from acid mine waste extremophiles.Stierle AA, Stierle DB.  Nat Prod Commun. 2014 Jul;9(7):1037-44.  Related citations

Phomopsolides and related compounds from the alga-associated fungus, Penicillium  clavigerum.. Stierle AA, Stierle DB, Mitman GG, Snyder S, Antczak C, Djaballah H.  Nat Prod Commun. 2014 Jan;9(1):87-90. Related citations

Bioprospecting in the Berkeley Pit: the Use of Signal Transduction Enzyme Inhibition Assays to Isolate Bioactive Secondary Metabolites from the Extremophilic Fungi of an Acid Mine Waste Lake. Andrea Stierle and Donald Stierle.  2013. In: “Bioactive Natural Products”  Atta-Ur-Rahman, Ed.; Elsevier Science Publishers: Amsterdam.  pp. 1-47.

Caspase-1 inhibitors from an extremophilic fungus that target specific leukemia cell lines  Stierle AA, Stierle DB, Girtsman T. J Nat Prod. 2012 Mar 23;75(3):344-50. Free full text Related citations

Caspase-1 and -3 inhibiting drimane sesquiterpenoids from the extremophilic fungus Penicillium solitum . Stierle DB, Stierle AA, Girtsman T, McIntyre K, Nichols J. J Nat Prod. 2012 Feb 24;75(2):262-6. Free full text Cited in PMC Related citations

Berkeleyones and related meroterpenes from a deep water acid mine waste fungus that inhibit the production of interleukin 1-β from induced inflamma-somes. Stierle DB, Stierle AA, Patacini B, McIntyre K, Girtsman T, Bolstad E. J Nat Prod. 2011 Oct 28;74(10):2273-7. Free full text Cited in PMC Related citations

Anticancer compounds derived from fungal endo-phytes: their importance and future challenges. Kharwar RN, Mishra A, Gond SK, Stierle A, Stierle D Nat Prod Rep. 2011 Jul;28(7):1208-28. Cited in PMC Related citations

The berkeleyamides, amides from the acid lake fungus Penicillum rubrum.  Stierle AA, Stierle DB, Patacini B. J Nat Prod. 2008 May;71(5):856-60.  Cited in PMC Related citations

The berkeleyacetals, three meroterpenes from a deep water acid mine waste Penicillium . Stierle DB, Stierle AA, Patacini B. J Nat Prod. 2007 Nov;70(11):1820-3. Epub 2007 Oct 31. Free full text Cited in PMC Related citations

Berkelic acid, a novel spiroketal with selective anticancer activity from an acid mine waste fungal extremophile.  Stierle AA, Stierle DB, Kelly K.  J Org Chem. 2006 Jul 7;71(14):5357-60. Cited in PMC Related citations

Andrea Stierle and Donald Stierle.  Bioprospecting in the Berkeley Pit: Bioactive Metabolites from Acid Mine Waste Extremophiles.  In: “Bioactive Natural Products”, Volume 32, Atta-Ur-Rahman, Ed.; Elsevier Science Publishers: Amsterdam. 2005

Novel sesquiterpenoid matrix metalloproteinase-3 inhibitors from an acid mine waste extremophile. Stierle AA, Stierle DB, Kemp K.  J Nat Prod. 2004 Aug;67(8):1392-5. Cited in PMC Related citations

Berkeleydione and berkeleytrione, new bioactive metabolites from an acid mine organism . Stierle DB, Stierle AA, Hobbs JD, Stokken J, Clardy J. Org Lett. 2004 Mar 18;6(6):1049-52.   Cited in PMC Related citations

 

Publications

All Publications

 A Stierle, D  Stierle  2016  Secondary Metabolites of Acid Mine Waste Fungi. In "Topics in Biodiversity and Conservation", D Hawksworth, RRM Patterson (Eds), Springer, in press

Azaphilones from an Acid Mine Extremophile Strain of a Pleurostomophora sp  Stierle AA, Stierle DB, Girtsman T, Mou TC, Antczak C, Djaballah H.  J Nat Prod. 2015 Dec 24;78(12):2917-23

Bioactive Secondary Metabolites Produced by the Fungal Endophytes of Conifers. Stierle AA, Stierle DB.  Nat Prod Commun. 2015 Oct;10(10):1671-82.

Crystal structure and absolute configuration of preaustinoid A1 Stierle A, Stierle D, Decato D. . Acta Crystallogr E Crystallogr Commun. 2015 Jul 22;71(Pt 8):o596-7. Free full text Related citations

Redetermination and absolute configuration of berkeleydione  Stierle A, Stierle D, Decato D. . Acta Crystallogr E Crystallogr Commun. 2015 Mar 21;71(Pt 4):o248. Free full text Related citations

Bioactive secondary metabolites from acid mine waste extremophiles.Stierle AA, Stierle DB.  Nat Prod Commun. 2014 Jul;9(7):1037-44.  Related citations

Phomopsolides and related compounds from the alga-associated fungus, Penicillium  clavigerum.. Stierle AA, Stierle DB, Mitman GG, Snyder S, Antczak C, Djaballah H.  Nat Prod Commun. 2014 Jan;9(1):87-90. Related citations

Caspase-1 inhibitors from an extremophilic fungus that target specific leukemia cell lines  Stierle AA, Stierle DB, Girtsman T. . J Nat Prod. 2012 Mar 23;75(3):344-50. Free full text Related citations

Caspase-1 and -3 inhibiting drimane sesquiterpenoids from the extremophilic fungus Penicillium solitum . Stierle DB, Stierle AA, Girtsman T, McIntyre K, Nichols J. . J Nat Prod. 2012 Feb 24;75(2):262-6. Free full text Cited in PMC Related citations

Berkeleyones and related meroterpenes from a deep water acid mine waste fungus that inhibit the production of interleukin 1-β from induced inflammasomes. Stierle DB, Stierle AA, Patacini B, McIntyre K, Girtsman T, Bolstad E. . J Nat Prod. 2011 Oct 28;74(10):2273-7. Free full text Cited in PMC Related citations

Anticancer compounds derived from fungal endophytes: their importance and future challenges. Kharwar RN, Mishra A, Gond SK, Stierle A, Stierle D Nat Prod Rep. 2011 Jul;28(7):1208-28. Cited in PMC Related citations

The berkeleyamides, amides from the acid lake fungus Penicillum rubrum.  Stierle AA, Stierle DB, Patacini B. J Nat Prod. 2008 May;71(5):856-60.  Cited in PMC Related citations

The berkeleyacetals, three meroterpenes from a deep water acid mine waste Penicillium . Stierle DB, Stierle AA, Patacini B. J Nat Prod. 2007 Nov;70(11):1820-3. Epub 2007 Oct 31. Free full text Cited in PMC Related citations

Berkelic acid, a novel spiroketal with selective anticancer activity from an acid mine waste fungal extremophile.  Stierle AA, Stierle DB, Kelly K.  J Org Chem. 2006 Jul 7;71(14):5357-60. Cited in PMC Related citations

Novel sesquiterpenoid matrix metalloproteinase-3 inhibitors from an acid mine waste extremophile. Stierle AA, Stierle DB, Kemp K.  J Nat Prod. 2004 Aug;67(8):1392-5. Cited in PMC Related citations

Berkeleydione and berkeleytrione, new bioactive metabolites from an acid mine organism . Stierle DB, Stierle AA, Hobbs JD, Stokken J, Clardy J. Org Lett. 2004 Mar 18;6(6):1049-52.   Cited in PMC Related citations

Sequoiamonascins: novel antitumor metabolites of the redwood endophyte, Aspergillus parasiticus. Donald B. Stierle, Andrea Stierle, Timothy Bugni. 2003.     J.Org. Chem.  68: 4966-4967

A Novel 5-HT Receptor Ligand and Related Cytotoxic Compounds from an Acid Mine Waste Extremophile. AA. Stierle, DB. Stierle, K Parker, E Goldstein, T Bugni, C Baarson, J Gress, D Blake. 2003.   J.Nat.Prod., 66: 1097-1100.

Sequoiatones C-f, constituents of the redwood endophyte Aspergillus parasiticus.  Stierle AA, Stierle DB, Bugni T. J Nat Prod. 2001 Oct;64(10):1350-3. Cited in PMC Related citations

Bioactive compounds from four  endophytic Penicillium sp. isolated from the northwest Pacific yew tree. AA. Stierle, DB. Stierle. In:   “Bioactive Natural  Products”, Atta-Ur-Rahman, Ed.; Elsevier Science Publishers: Amsterdam. Vol. 24. 2000, pp 933-978.

Isolation of two highly methylated polyketide derivatives from a yew-associated penicillium species Stierle DB, Stierle AA, Ganser BK. J Nat Prod. 1999 Aug;62(8):1147-50. Related citations

Sequoiatones A and B: Novel Antitumor Metabolites Isolated from a Redwood Endophyte.  Stierle AA, Stierle DB, Bugni T.  J Org Chem. 1999 Jul 23;64(15):5479-5484. Cited in PMC Related citations

Dihydroramulosin from Botrytis sp Stierle DB, Stierle AA, Kunz A. . J Nat Prod. 1998 Oct;61(10):1277-8. Cited in PMCRelated citations

Gloeolactone, a New Epoxy Lactone from a Blue-Green Alga.  Stierle DB, Stierle AA, Bugni T, Loewen G.  J Nat Prod. 1998 Feb 27;61(2):251-2. Related citations

New phomopsolides from a Penicillium sp. Stierle DB, Stierle AA, Ganser B.  J Nat Prod. 1997 Nov;60(11):1207-9. Related citations

The search for a taxol-producing microorganism among the endophytic fungi of the Pacific yew, Taxus brevifolia. Stierle A, Strobel G, Stierle D, Grothaus P, Bignami G.  J Nat Prod. 1995 Sep;58(9):1315-24. Cited in PMC Related citations

Bioactive metabolites of the endophytic fungi of Pacific yew, Taxus brevifolia: paclitaxel, taxanes, and other bioactve compounds.  A Stierle, D Stierle, G Strobel, G Bgnami, P Grothaus.  In “Taxane Anticancer Agents: Basic Science and Current Status”. Eds., G.I.Georg; T.T.Chen; I.Ojima and D.M.Vyas.  ACS Symposium Series 583, Washington, DC, 1995, 81-97.

Investigation of endophytic fungi of Pacific yew. A Stierle, D Stierle, G Strobel, G Bignami, P Grothausin "Bioregulators and Natural Products".  Ed., P.Hedin, ACS Symposium Series 557, Washington, DC, 1994, 64-77.

Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Stierle A, Strobel G, Stierle D.  Science. 1993 Apr 9;260(5105):214-6. Cited in PMC Related citations

Taxomyces andreanae, a proposed new taxon for a bulbilliferous hyphomycete associated with Pacific Yew (Taxus brevifolia). G.A. Strobel, A. Stierle and D. Stierle. 1993 Mycotaxon 47:71.

D.B. Stierle and A.A. Stierle. Pseudomonic acid derivatives from a marine bacterium. Experientia 48(11-12), 1165-1169 (1992).

Analytical Methods for Phytotoxins . A. Stierle, G.A. Strobel, D Stierle and Fumio Sugawara. .  In "Methods of Plant Analysis"; Eds., H.F. Linskens and J.F. Jackson. Springer Verlag Press: Berlin, 1992,  1-32.

Antimicrobial N-methylpyridinium salts related to the xestamines from the Caribbean sponge Calyx podatypa.Stierle DB, Faulkner DJ.  J Nat Prod. 1991 Jul-Aug;54(4):1134-6. Related citations

Two New Pyrroloquinoline Alkaloids From the Sponge Dramiria Sp. DB Stierle, DJ Faulkner.  J.Nat. Prod54, 1131 (1991)

D. B. Stierle, E. H. Biehl, and P. C. Reeves. Cyclobutadieneiron tricarbonyl Carboxylic Acids:  Synthesis and Acidity. J. Organometal. Chem., 72, 221 (1974).

D. B. Stierle, R. M. Wing and J. J. Sims. Marine Natural Products XI:  Costatone and Costatolide, New Halogenated Monoterpenes from the Red Seaweed Plocamium costatum. Tetrahedron Letters 4455 (1976).

D. B. Stierle and J. J. Sims. Marine Natural Products XV:  Polyhalogenated Cyclic Monoterpenes from the Red Alga Plocamium cartilagineum of Antarctica. Tetrahedron 35, 1261 (1979).D. B. Stierle, R. N. Wing and J. J. Sims. Marine Natural Products XVI:  Polyhalogenated Acyclic Monoterpenes from the Red Alga Plocamium of Antarctica.  Tetrahedron 35, 2855 (1979).

D. B. Stierle and D. J. Faulkner.  Metabolites of the Marine Sponge Chondrosia collectrixJ. Org. Chem. 44, 964 (1979).

W. C. M. C. Kokke, C. Tarchine, D. B. Stierle, and C. Djerassi.  Isolation, Structure Elucidation and Partial Synthesis of Xestosterol, a Biosynthetically Significant Sterol from the Sponge Xestospongia mutaJOrg. Chem. 44, 3385 (1979).

D. J. Faulkner, R. W. Armstrong, P. Djura, D. B. Stierle and S. J. Wratten.  Some Chemical Constituents of Caribbean Sponges, Colloq. Int. C. N. R. S. 291, 401 (1979).

P. Djura, D. B. Stierle, B. Sullivan and D. J. Faulkner.  Some Metabolites of the Marine Sponges Smenospongia aurea and Smenospongia (Polyfibrospongia) echinaJ. Org. Chem. 45, 1435 (1980).

D.B.Stierle, B. Carte, D.J. Faulkner, B.Tagle and J.Clardy.  The Asbestinins, a novel class of Diterpenes from the Gorgonian Briareum asbestinin. J.Am.Chem.Soc. 102, 5988 (1980).

D. B. Stierle and D. J. Faulkner.  Metabolites of three Marine Sponges of the Genus PlakortisJ. Org. Chem. 45, 3396 (1980).

D. B. Stierle and D. J. Faulkner.  Interesting New Cyanohydrins from the Marine Sponge LaxosuberitesJ. Org. Chem. 45, 4980 (1980).

R. R. Izac, D. B. Stierle and J. J. Sims.  Sulfur and N-methylforamide from the Red Alga Erythrophyllum delesseriodes. Phytochemistry 21, 229 (1982).

D. B. Stierle and J. J. Sims.  Plocamenone:  A Unique Halogenated Monoterpene from PlocamiumTetrahedron Letters 153 (1984).

D. B. Stierle. Germacranolides from Chaenactis douglasii. Phytochemistry 25, 743 (1986).

A. M. S. Mayer, L. Krotz, R. D. Bonfil, O. D. Bustuoabad, J. F. Groisman, R. M. de Lederkremer and D. B. Stierle.  Biological Activity in Macrocystis pyrifera from Argentina.  Hydrobiologia, 151/152, 483 (1987).

D. B. Stierle, A. A. Stierle and R. D. Larsen.  The Constituents of Polemonium viscosumPhytochemistry, 27, 517 (1988).

R. R. West, J. H. Cardellina and D. B. Stierle.  Metal Bioaccumulation in Sponges.  Proceedings of the Montana Academy of Sciences, 50, 121 (1990).

D. B. Stierle and D. J. Faulkner.  Two New Pyrroloquinoline Alkaloids From the Sponge Dramiria Sp., J.Nat. Prod, 54, 1131 (1991).