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Dr David Miller
(e/fe)
MA (Oxon), PhD (Soton), MRSC, CChem, SFHEA
- Ar gael fel goruchwyliwr ôl-raddedig
Timau a rolau for David Miller
Uwch Ddarlithydd mewn Cemeg Organig a Biolegol. Cydlynydd PGT, Adran Cemeg ac Arweinydd Profiad Myfyrwyr PGT, Ysgol y Gwyddorau Ffisegol, Cemegol ac Amgylcheddol
Trosolwyg
Mae gen i ddiddordeb yn y defnydd o gemeg organig synthetig fel y'i cymhwysir i ddatrys problemau biolegol ac i'r gwrthwyneb. Yn aml, gellir ymchwilio i'r ddealltwriaeth o sut mae macromolecwlau natur fel proteinau a DNA yn gweithio a rhyngweithio â'i gilydd trwy ddefnyddio moleciwlau organig bach. Yn aml, nid yw moleciwlau o'r fath ar gael o'r pwll naturiol ac felly mae'r cemegydd synthetig yn ganolog i ddatrys problemau o'r fath. Yn yr un modd, gall cemeg synthetig er ei bod yn gallu paratoi'r moleciwlau mwyaf cymhleth a chymhleth yn aml ond wneud hynny ar draul fawr o amser ac adnoddau. Mae systemau naturiol, os cânt eu harneisio'n gywir yn cynnig cyfle i adeiladu moleciwlau o gymhlethdod o'r fath yn llawer cyflymach ac yn fwy effeithlon.
Rwy'n cynnig prosiectau BSc mewn ymchwil addysg.
Cyhoeddiad
2026
- Srivastava, P. L. , Miller, D. J. and Allemann, R. K. 2026. Designed water capture in terpene synthase catalysis. ChemBioChem 27 (5) e70265. (10.1002/cbic.70265)
2024
- González Requena, V. et al. 2024. Single point mutation abolishes water capture in germacradien‐4‐ol synthase. ChemBioChem 25 (23) e202400290. (10.1002/cbic.202400290)
- Srivastava, P. L. et al. 2024. Simulation-guided engineering enables a functional switch in selinadiene synthase toward hydroxylation. ACS Catalysis 14 (14), pp.11034–11043. (10.1021/acscatal.4c02032)
- Srivastava, P. L. et al. 2024. Production of non-natural terpenoids through chemoenzymatic synthesis using substrate analogs. In: Rudolf, J. ed. Methods in Enzymology. Elsevier. , pp.207-230. (10.1016/bs.mie.2024.03.015)
2023
- Srivastava, P. et al. 2023. Active site loop engineering abolishes water capture in hydroxylating sesquiterpene synthases. ACS Catalysis 13 (21), pp.14199-14204. (10.1021/acscatal.3c03920)
2021
- Srivastava, P. L. et al. 2021. Redesigning the molecular choreography to prevent hydroxylation in Germacradien-11-ol synthase catalysis. ACS Catalysis 11 (3), pp.1033–1041. (10.1021/acscatal.0c04647)
2020
- Cresser-Brown, J. et al. 2020. An unexpected co-crystal structure of the calpain PEF(S) domain with Hfq reveals a potential chaperone function of Hfq. Acta Crystallographica Section F: Structural Biology Communications 76 (2), pp.81-85. (10.1107/S2053230X20001181)
2019
- Demiray, M. , Miller, D. J. and Allemann, R. K. 2019. Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids. Beilstein Journal of Organic Chemistry 15 , pp.2184-2190. (10.3762/bjoc.15.215)
- Loizzi, M. , Miller, D. J. and Allemann, R. K. 2019. Silent catalytic promiscuity in the high-fidelity terpene cyclase δ-cadinene synthase. Organic & Biomolecular Chemistry 17 (5), pp.1206-1214. (10.1039/C8OB02821D)
2018
- Kalash, L. et al., 2018. Structure-based design of allosteric calpain-1 inhibitors populating a novel bioactivity space. European Journal of Medicinal Chemistry 157 , pp.1264-1275. (10.1016/j.ejmech.2018.08.049)
- Huynh, F. et al. 2018. Sesquiterpene synthase-catalysed formation of a new medium-sized cyclic terpenoid ether from farnesyl diphosphate analogues. Chembiochem 19 (17), pp.1834-1838. (10.1002/cbic.201800218)
- Loizzi, M. et al. 2018. Nucleophilic water capture or proton loss: single amino acid switch converts δ-Cadinene synthase into germacradien-4-ol synthase. Chembiochem 19 (1), pp.100-105. (10.1002/cbic.201700531)
- Yaldizli, Ö. et al., 2018. Response to the commentary of Yates RL and DeLuca GC on the study: HLA-DRB1*1501 associations with magnetic resonance imaging measures of grey matter pathology in multiple sclerosis. Multiple Sclerosis and Related Disorders 19 , pp.168-170. (10.1016/j.msard.2016.08.006)
2015
- Adams, S. et al., 2015. Conformationally restricted calpain inhibitors. Chemical Science 6 (12), pp.6865-6871. (10.1039/c5sc01158b)
- Touchet, S. et al., 2015. Novel olfactory ligands via terpene synthases. Chemical Communications 51 (35), pp.7550-7553. (10.1039/C5CC01814E)
2014
- Adams, S. E. et al. 2014. The structural basis of differential inhibition of human calpain by indole and phenyl α--mercaptoacrylic acids. Journal of Structural Biology 187 (3), pp.236-241. (10.1016/j.jsb.2014.07.004)
2013
- Li, J. et al., 2013. Rational engineering of plasticity residues of sesquiterpene synthases from Artemisia annua: Product specificity and catalytic efficiency. Biochemical Journal 451 (3), pp.417-426. (10.1042/BJ20130041)
- Miller, D. J. et al. 2013. Calpain-1 inhibitors for selective treatment of rheumatoid arthritis: what is the future?. Future Medicinal Chemistry 5 (17), pp.2057-2074. (10.4155/fmc.13.172)
2012
- Adams, S. E. et al. 2012. Potent inhibition of Ca2+-dependent activation of calpain-1 by novel mercaptoacrylates. MedChemComm 3 (5), pp.566-570. (10.1039/c2md00280a)
- Cascón, O. et al. 2012. Chemoenzymatic preparation of germacrene analogues. Chemical Communications 48 (78), pp.9702-9704. (10.1039/c2cc35542f)
- Faraldos, J. A. et al. 2012. A 1,6-ring closure mechanism for (+)-δ-cadinene synthase?. Journal of the American Chemical Society 134 (13), pp.5900-5908. (10.1021/ja211820p)
- Miller, D. J. and Allemann, R. K. 2012. Sesquiterpene synthases: Passive catalysts or active players?. Natural Product Reports 29 (1), pp.60-71. (10.1039/c1np00060h)
- Yoosuf-Aly, Z. et al. 2012. Chemoenzymatic synthesis of the alarm pheromone (+)-verbenone from geranyl diphosphate. Chemical Communications 48 , pp.7040-7042. (10.1039/c2cc32883f)
2009
- Gennadios, H. A. et al., 2009. Crystal structure of (+)-δ-cadinene synthase from Gossypium arboreum and evolutionary divergence of metal binding motifs for catalysis. Biochemistry 48 (26), pp.6175-6183. (10.1021/bi900483b)
- Miller, D. J. et al. 2009. 6- and 14-Fluoro farnesyl diphosphate: mechanistic probes for the reaction catalysed by aristolochene synthase. Organic & Biomolecular Chemistry 7 (5), pp.962-975. (10.1039/b817194g)
2008
- Miller, D. J. et al. 2008. Stereochemistry of eudesmane cation formation during catalysis by aristolochene synthase from Penicillium roqueforti. Organic & Biomolecular Chemistry 6 (13), pp.2346-2354. (10.1039/b804198a)
- Miller, D. J. , Yu, F. and Allemann, R. K. 2008. FLUO 14-Study of sesquiterpene cyclization reactions using fluorinated farnesyl diphosphate analogs. Abstracts of Papers of the American Chemical Society 236
- Shishova, E. Y. et al., 2008. X-ray crystallographic studies of substrate binding to aristolochene synthase suggest a metal ion binding sequence for catalysis. Journal of Biological Chemistry 283 (22), pp.15431-15439. (10.1074/jbc.M800659200)
2007
- Miller, D. J. , Yu, F. and Allemann, R. K. 2007. Aristolochene synthase-catalyzed cyclization of 2-fluorofarnesyl-diphosphate to 2-fluorogermacrene A. Chembiochem 8 (15), pp.1819-1825. (10.1002/cbic.200700219)
- Miller, D. J. et al. 2007. Competitive inhibition of aristolochene synthase by phenyl-substituted farnesyl diphosphates: evidence of active site plasticity. Organic & Biomolecular Chemistry 5 (20), pp.3287-3298. (10.1039/b713301b)
- Yu, F. , Miller, D. J. and Allemann, R. K. 2007. Probing the reaction mechanism of aristolochene synthase with 12,13-difluorofarnesyl diphosphate. Chemical Communications- Royal Society of Chemistry (40), pp.4155-4157. (10.1039/b709562g)
2006
- Nicoll, A. J. et al., 2006. Designed high affinity Cu2+ -Binding α-Helical foldamer. Journal of the American Chemical Society 128 (28), pp.9187-9193. (10.1021/ja061513u)
2004
- Miller, D. J. et al. 2004. Removal of the phosphate group in mechanism-based inhibitors of inositol monophosphatase leads to unusual inhibitory activity. Organic & Biomolecular Chemistry 2 (5), pp.671-688. (10.1039/b312808c)
2003
- Bashir-Uddin Surfraz, M. et al., 2003. Product-like inhibitors of inositol monophosphatase. Tetrahedron Letters 44 (41), pp.7677-7679. (10.1016/S0040-4039(03)01878-1)
2000
- Miller, D. J. et al. 2000. The 6-OH Group of D -Inositol 1-PhosphateServes as an H-Bond Donor in the Catalytic Hydrolysis of the Phosphate Ester by Inositol Monophosphatase. ChemBioChem 1 (4), pp.262-271. (10.1002/1439-7633(20001117)1:4%3C262::AID-CBIC262%3E3.0.CO;2-%23)
1998
- Andersen, J. M. et al., 1998. Preparation and catalytic properties of resin bound binuclear rhodium tetracarboxylate complexes. Tetrahedron Letters 39 (42), pp.7815-7818. (10.1016/S0040-4039(98)01709-2)
- Miller, D. J. et al. 1998. Aminoalkylphosphinate inhibitors of D-Ala-D-Ala adding enzyme. Journal of the Chemical Society, Perkin Transactions 1 (1), pp.131-132. (10.1039/a704097k)
- Stones, D. et al., 1998. A method for the quantification of resin loading using 19F gel phase NMR spectroscopy and a new method for benzyl ether linker cleavage in solid phase chemistry. Tetrahedron Letters 39 (27), pp.4875-4878. (10.1016/S0040-4039(98)00883-1)
Adrannau llyfrau
- Srivastava, P. L. et al. 2024. Production of non-natural terpenoids through chemoenzymatic synthesis using substrate analogs. In: Rudolf, J. ed. Methods in Enzymology. Elsevier. , pp.207-230. (10.1016/bs.mie.2024.03.015)
Erthyglau
- Srivastava, P. L. , Miller, D. J. and Allemann, R. K. 2026. Designed water capture in terpene synthase catalysis. ChemBioChem 27 (5) e70265. (10.1002/cbic.70265)
- González Requena, V. et al. 2024. Single point mutation abolishes water capture in germacradien‐4‐ol synthase. ChemBioChem 25 (23) e202400290. (10.1002/cbic.202400290)
- Srivastava, P. L. et al. 2024. Simulation-guided engineering enables a functional switch in selinadiene synthase toward hydroxylation. ACS Catalysis 14 (14), pp.11034–11043. (10.1021/acscatal.4c02032)
- Srivastava, P. et al. 2023. Active site loop engineering abolishes water capture in hydroxylating sesquiterpene synthases. ACS Catalysis 13 (21), pp.14199-14204. (10.1021/acscatal.3c03920)
- Srivastava, P. L. et al. 2021. Redesigning the molecular choreography to prevent hydroxylation in Germacradien-11-ol synthase catalysis. ACS Catalysis 11 (3), pp.1033–1041. (10.1021/acscatal.0c04647)
- Cresser-Brown, J. et al. 2020. An unexpected co-crystal structure of the calpain PEF(S) domain with Hfq reveals a potential chaperone function of Hfq. Acta Crystallographica Section F: Structural Biology Communications 76 (2), pp.81-85. (10.1107/S2053230X20001181)
- Demiray, M. , Miller, D. J. and Allemann, R. K. 2019. Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids. Beilstein Journal of Organic Chemistry 15 , pp.2184-2190. (10.3762/bjoc.15.215)
- Loizzi, M. , Miller, D. J. and Allemann, R. K. 2019. Silent catalytic promiscuity in the high-fidelity terpene cyclase δ-cadinene synthase. Organic & Biomolecular Chemistry 17 (5), pp.1206-1214. (10.1039/C8OB02821D)
- Kalash, L. et al., 2018. Structure-based design of allosteric calpain-1 inhibitors populating a novel bioactivity space. European Journal of Medicinal Chemistry 157 , pp.1264-1275. (10.1016/j.ejmech.2018.08.049)
- Huynh, F. et al. 2018. Sesquiterpene synthase-catalysed formation of a new medium-sized cyclic terpenoid ether from farnesyl diphosphate analogues. Chembiochem 19 (17), pp.1834-1838. (10.1002/cbic.201800218)
- Loizzi, M. et al. 2018. Nucleophilic water capture or proton loss: single amino acid switch converts δ-Cadinene synthase into germacradien-4-ol synthase. Chembiochem 19 (1), pp.100-105. (10.1002/cbic.201700531)
- Yaldizli, Ö. et al., 2018. Response to the commentary of Yates RL and DeLuca GC on the study: HLA-DRB1*1501 associations with magnetic resonance imaging measures of grey matter pathology in multiple sclerosis. Multiple Sclerosis and Related Disorders 19 , pp.168-170. (10.1016/j.msard.2016.08.006)
- Adams, S. et al., 2015. Conformationally restricted calpain inhibitors. Chemical Science 6 (12), pp.6865-6871. (10.1039/c5sc01158b)
- Touchet, S. et al., 2015. Novel olfactory ligands via terpene synthases. Chemical Communications 51 (35), pp.7550-7553. (10.1039/C5CC01814E)
- Adams, S. E. et al. 2014. The structural basis of differential inhibition of human calpain by indole and phenyl α--mercaptoacrylic acids. Journal of Structural Biology 187 (3), pp.236-241. (10.1016/j.jsb.2014.07.004)
- Li, J. et al., 2013. Rational engineering of plasticity residues of sesquiterpene synthases from Artemisia annua: Product specificity and catalytic efficiency. Biochemical Journal 451 (3), pp.417-426. (10.1042/BJ20130041)
- Miller, D. J. et al. 2013. Calpain-1 inhibitors for selective treatment of rheumatoid arthritis: what is the future?. Future Medicinal Chemistry 5 (17), pp.2057-2074. (10.4155/fmc.13.172)
- Adams, S. E. et al. 2012. Potent inhibition of Ca2+-dependent activation of calpain-1 by novel mercaptoacrylates. MedChemComm 3 (5), pp.566-570. (10.1039/c2md00280a)
- Cascón, O. et al. 2012. Chemoenzymatic preparation of germacrene analogues. Chemical Communications 48 (78), pp.9702-9704. (10.1039/c2cc35542f)
- Faraldos, J. A. et al. 2012. A 1,6-ring closure mechanism for (+)-δ-cadinene synthase?. Journal of the American Chemical Society 134 (13), pp.5900-5908. (10.1021/ja211820p)
- Miller, D. J. and Allemann, R. K. 2012. Sesquiterpene synthases: Passive catalysts or active players?. Natural Product Reports 29 (1), pp.60-71. (10.1039/c1np00060h)
- Yoosuf-Aly, Z. et al. 2012. Chemoenzymatic synthesis of the alarm pheromone (+)-verbenone from geranyl diphosphate. Chemical Communications 48 , pp.7040-7042. (10.1039/c2cc32883f)
- Gennadios, H. A. et al., 2009. Crystal structure of (+)-δ-cadinene synthase from Gossypium arboreum and evolutionary divergence of metal binding motifs for catalysis. Biochemistry 48 (26), pp.6175-6183. (10.1021/bi900483b)
- Miller, D. J. et al. 2009. 6- and 14-Fluoro farnesyl diphosphate: mechanistic probes for the reaction catalysed by aristolochene synthase. Organic & Biomolecular Chemistry 7 (5), pp.962-975. (10.1039/b817194g)
- Miller, D. J. et al. 2008. Stereochemistry of eudesmane cation formation during catalysis by aristolochene synthase from Penicillium roqueforti. Organic & Biomolecular Chemistry 6 (13), pp.2346-2354. (10.1039/b804198a)
- Miller, D. J. , Yu, F. and Allemann, R. K. 2008. FLUO 14-Study of sesquiterpene cyclization reactions using fluorinated farnesyl diphosphate analogs. Abstracts of Papers of the American Chemical Society 236
- Shishova, E. Y. et al., 2008. X-ray crystallographic studies of substrate binding to aristolochene synthase suggest a metal ion binding sequence for catalysis. Journal of Biological Chemistry 283 (22), pp.15431-15439. (10.1074/jbc.M800659200)
- Miller, D. J. , Yu, F. and Allemann, R. K. 2007. Aristolochene synthase-catalyzed cyclization of 2-fluorofarnesyl-diphosphate to 2-fluorogermacrene A. Chembiochem 8 (15), pp.1819-1825. (10.1002/cbic.200700219)
- Miller, D. J. et al. 2007. Competitive inhibition of aristolochene synthase by phenyl-substituted farnesyl diphosphates: evidence of active site plasticity. Organic & Biomolecular Chemistry 5 (20), pp.3287-3298. (10.1039/b713301b)
- Yu, F. , Miller, D. J. and Allemann, R. K. 2007. Probing the reaction mechanism of aristolochene synthase with 12,13-difluorofarnesyl diphosphate. Chemical Communications- Royal Society of Chemistry (40), pp.4155-4157. (10.1039/b709562g)
- Nicoll, A. J. et al., 2006. Designed high affinity Cu2+ -Binding α-Helical foldamer. Journal of the American Chemical Society 128 (28), pp.9187-9193. (10.1021/ja061513u)
- Miller, D. J. et al. 2004. Removal of the phosphate group in mechanism-based inhibitors of inositol monophosphatase leads to unusual inhibitory activity. Organic & Biomolecular Chemistry 2 (5), pp.671-688. (10.1039/b312808c)
- Bashir-Uddin Surfraz, M. et al., 2003. Product-like inhibitors of inositol monophosphatase. Tetrahedron Letters 44 (41), pp.7677-7679. (10.1016/S0040-4039(03)01878-1)
- Miller, D. J. et al. 2000. The 6-OH Group of D -Inositol 1-PhosphateServes as an H-Bond Donor in the Catalytic Hydrolysis of the Phosphate Ester by Inositol Monophosphatase. ChemBioChem 1 (4), pp.262-271. (10.1002/1439-7633(20001117)1:4%3C262::AID-CBIC262%3E3.0.CO;2-%23)
- Andersen, J. M. et al., 1998. Preparation and catalytic properties of resin bound binuclear rhodium tetracarboxylate complexes. Tetrahedron Letters 39 (42), pp.7815-7818. (10.1016/S0040-4039(98)01709-2)
- Miller, D. J. et al. 1998. Aminoalkylphosphinate inhibitors of D-Ala-D-Ala adding enzyme. Journal of the Chemical Society, Perkin Transactions 1 (1), pp.131-132. (10.1039/a704097k)
- Stones, D. et al., 1998. A method for the quantification of resin loading using 19F gel phase NMR spectroscopy and a new method for benzyl ether linker cleavage in solid phase chemistry. Tetrahedron Letters 39 (27), pp.4875-4878. (10.1016/S0040-4039(98)00883-1)
Ymchwil
I am interested in the use of synthetic organic chemistry as applied to the solution of biological problems and vice versa. The understanding of how Nature$acirc; s macromolecules such as proteins and DNA work and interact with one another can often be probed by use of small organic molecules. Such molecules are often not available from the natural pool and so the synthetic chemist is central to solving such problems. Similarly, synthetic chemistry although well capable of preparing the most complex and intricate of molecules can often only do so at great expense of time and resources. Natural systems, if harnessed correctly offer the opportunity to construct molecules of such complexity much more quickly and efficiently.
Inositol monophoshphatase.
Inositol monophosphatase is an enzyme that is involved in a crucial signal transduction pathway within our cells that has been implicated as a target for drugs that treat bipolar disorders. We are interested in the study of the mechanism of action of this enzyme and in the discovery of new inhibitors that may ultimately lead to better treatments for this debilitating condition.
mu-Calpain
Calpains are cysteine proteases that are activated by calcium ions. mu-Calpain is a member of this family of enzymes that appears to have a key role in cell-membrane expansion and hence motility of white blood cells (neutrophils). Development of potent and selective mu-calpain inhibitors may lead to a treatment for a variety of autoimmune diseases such as osteoarthritis.
Biosynthesis of terpenoids
Terpenes are the largest and most diverse group of natural products but originate from only a tiny group of prenyl diphosphate precursors. Diversity is generated in nature by the structurally similar terpene cyclases that form many different products from each prenyl diphosphate. By a combination of chemical synthesis, enzymology and molecular biology we seek to understand how such diversity can be created by enzymes that share a common fold.
Addysgu
CH5103 Sylfeini Cemeg Organig
CH5130 Cyflwyniad i Ddatblygu Cyffuriau
CH5306 Dulliau Newydd mewn Darganfod Cyffuriau
CH3317 Biosynthesis Peirianneg
CHT232 Sgiliau Allweddol
CHT3589 Biocatalysis ar gyfer Dyfodol Cynaliadwy
CHT550 Cymwysiadau dulliau ymchwil.
CHT327 Biosynthesis Peirianneg
Cemeg Craidd CHT600 ar gyfer Cynaliadwyedd
Bywgraffiad
MA mewn Cemeg gyda Chemeg Cwantwm Atodol, Coleg Oriel Rhydychen, 1989-1993., PhD, Prifysgol Southampton (o dan yr Athro T. D. H. Bugg) 1993-1997. Cynorthwyydd Ymchwil Ôl-ddoethurol, Prifysgol St. Andrews 1997-1998. Cynorthwy-ydd Ymchwil Ôl-ddoethurol, Prifysgol Birmingham 1998-2005. Cymrawd Ymchwil Ôl-ddoethurol, Prifysgol Caerdydd 2005-2007. Cymrawd ymchwil 2007-2015. Darlithydd 2015-2022. Uwch Ddarlithydd 2022.
Aelodaethau proffesiynol
MRSC, CCHem
Meysydd goruchwyliaeth
Prosiectau BSc Addysg a Llenyddiaeth
BSc Prosiectau Tîm Cemeg Meddyginiaethol
Cyd-oruchwyliwr gyda'r Athro R K Allemann a'r Athro J A Pickett ar gyfer myfyrwyr PhD mewn biosynthesis terpenoid, proejcts meddyginiaethol, emiochemcial ac agrocemegol
Contact Details
Themâu ymchwil
Arbenigeddau
- Biosynthesis
- cemeg fiolegol
- Cemeg organig
- Pheromones a Semiochemicals eraill
- Biocatalysis a thechnoleg ensym