![David Miller MA (Oxon), PhD (Soton), MRSC, CChem, SFHEA](https://profiles-cardiff.imgix.net/attachments/1503?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Dr David Miller
(he/him)
MA (Oxon), PhD (Soton), MRSC, CChem, SFHEA
- Available for postgraduate supervision
Teams and roles for David Miller
Senior Lecturer in Organic and Biological Chemistry. PGT Coordinator, Department of Chemistry and PGT Student Experience Lead, School of Physical, Chemical and Environmental Sciences
Overview
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'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.
I offer BSc projects in education research.
Publication
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)
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)
- 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)
Research
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'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.
Teaching
CH5103 Foundations of Organic Chemistry
CH5130 Introduction to Drug Development
CH5306 New Modalities in Drug Discovery
CH3317 Engineering Biosynthesis
CHT232 Key Skills
CHT3589 Biocatalysis for a Sustainable Future
CHT550 Applications of Research methods.
CHT327 Engineering Biosynthesis
CHT600 Core Chemistry for Sustainability
Biography
MA in Chemistry with Supplementary Quantum Chemistry, Oriel College Oxford, 1989-1993., PhD, Southampton University (under Prof. T. D. H. Bugg) 1993-1997. Postdoctoral Research Assistant, University of St. Andrews 1997-1998. Postdoctoral Research Assistant, Birmingham University 1998-2005. Postdoctoral Research Fellow, Cardiff University 2005-2007. Research fellow 2007-2015. Lecturer 2015-2022. Senior Lecturer 2022.
Professional memberships
MRSC, CCHem
Supervisions
BSc Education and Literature projects
BSc Medicinal Chemistry Team projects
Co-Supervisor with Prof R K Allemann and Prof J A Pickett for PhD students in terpenoid biosynthesis, medicinal, emiochemcial and agrochemical proejcts
Contact Details
Research themes
Specialisms
- biosynthesis
- biological chemistry
- Organic chemistry
- Pheromones and other Semiochemicals
- Biocatalysis and enzyme technology