Yr Athro Nigel Richards

Athro Cemeg Biolegol

: RichardsN14@caerdydd.ac.uk
: +44 29208 76208

The Richards laboratory studies the relationship between the structure and function of enzymes that either catalyze chemically interesting reactions or are potential targets for the development of drugs against cancer or tuberculosis. In addition, several projects aimed at creating new tools for synthetic biology are underway, with an emphasis on enzymes that can manipulate DNA and RNA containing expanded genetic alphabets both in vitro and in live cells. Our work relies on an interdisciplinary approach at the interface of chemistry, physical organic chemistry, biophysics, biochemistry, molecular and cellular biology and medicinal chemistry and involves a wide range of techniques. For more information, click on the 'Research' tab above.

Date
Type

2023

Richards, N. G. J., Bearne, S. L., Goto, Y. and Parker, E. J. 2023. Reactivity and mechanism in chemical and synthetic biology. Philosophical Transactions of the Royal Society B: Biological Sciences 378(1871), article number: 20220023. (10.1098/rstb.2022.0023)
Li, W., Girt, G. C., Radadiya, A., Stewart, J. J. P., Richards, N. G. J. and Naismith, J. H. 2023. Experimental and computational snapshots of C-C bond formation in a C-nucleoside synthase. Open Biology 13(1), article number: 220287. (10.1098/rsob.220287)

2022

Bijani, S. et al. 2022. Novel dihydropyrimidinone derivatives as potential P-glycoprotein modulators. ACS Omega 7(19), pp. 16278-16287. (10.1021/acsomega.1c05839)

2021

Riegert, A. S., Narindoshvili, T., Coricello, A., Richards, N. G. J. and Raushel, F. M. 2021. Functional characterization of two PLP-dependent enzymes involved in capsular polysaccharide biosynthesis from campylobacter jejuni. Biochemistry 60(37), pp. 2836–2843. (10.1021/acs.biochem.1c00439)

2020

Ouaray, Z., Benner, S. A., Georgiadis, M. M. and Richards, N. G. J. 2020. Building better polymerases: Engineering the replication of expanded genetic alphabets. Journal of Biological Chemistry 295(50), pp. 17046-17059. (10.1074/jbc.REV120.013745)
Radadiya, A., Zhu, W., Coricello, A., Alcaro, S. and Richards, N. G. J. 2020. Improving the treatment of acute lymphoblastic leukemia. Biochemistry 59(35), pp. 3193-3200. (10.1021/acs.biochem.0c00354)
Gao, S. et al. 2020. Uncovering the chemistry of C–C bond formation in C-nucleoside biosynthesis: crystal structure of a C-glycoside synthase/PRPP complex. Chemical Communications 56(55), pp. 7617-7620. (10.1039/D0CC02834G)
Eberlein, L. et al. 2020. Tautomeric equilibria of nucleobases in the hachimoji expanded genetic alphabet. Journal of Chemical Theory and Computation 16(4), pp. 2766-2777. (10.1021/acs.jctc.9b01079)
Zhu, W., Liu, X., Hughes, M., de Crécy-Lagard, V. and Richards, N. G. J. 2020. Whole-genome sequence of Streptomyces kaniharaensis Shomura and Niida SF-557. Microbiology Resource Announcements 9(14), article number: e01434-19. (10.1128/MRA.01434-19)
Ouaray, Z., Singh, I., Georgiadis, M. M. and Richards, N. G. J. 2020. Building better enzymes: molecular basis of improved non-natural nucleobase incorporation by an evolved DNA polymerase. Protein Science 29(2) (10.1002/pro.3762)

2015

Hettmer, S. et al. 2015. Functional genomic screening reveals asparagine dependence as a metabolic vulnerability in sarcoma. eLife 4, article number: e09436. (10.7554/eLife.09436)
Georgiadis, M. M., Singh, I., Kellett, W. F., Hoshika, S., Benner, S. A. and Richards, N. G. J. 2015. Structural basis for a six nucleotide genetic alphabet. Journal of the American Chemical Society 137(21), pp. 6947-6955. (10.1021/jacs.5b03482)
Molt Jr., R. W., Lecher, A. M., Clark, T., Bartlett, R. J. and Richards, N. G. J. 2015. Facile Csp2-Csp2 bond cleavage in oxalic acid-derived radicals. Journal of the American Chemical Society 137(9), pp. 3248-3252. (10.1021/ja510666r)
Twahir, U. T., Stedwell, C. N., Lee, C. T., Richards, N. G. J., Polfer, N. C. and Angerhofer, A. 2015. Observation of superoxide production during catalysis of Bacillus subtilis oxalate decarboxylase at pH 4. Free Radical Biology and Medicine 80, pp. 59. (10.1016/j.freeradbiomed.2014.12.012)

2014

Miao, J., Richards, N. and Ge, H. 2014. Rhodium-catalyzed direct synthesis of unprotected NH-sulfoximines from sulfoxides. Chemical Communications- Royal Society of Chemistry 50(68), pp. 9687-9689. (10.1039/c4cc04349a)
Brunk, E., Kellett, W., Richards, N. and Rothlisberger, U. 2014. A mechanochemical switch to control radical intermediates. Biochemistry 53(23), pp. 3830-3838. (10.1021/bi500050k)
Campomanes, P. et al. 2014. Assigning the EPR fine structure parameters of the Mn(II) centers in bacillus subtilis oxalate decarboxylase by site-directed mutagenesis and DFT/MM calculations. Journal of the American Chemical Society 136(6), pp. 2313-2323. (10.1021/ja408138f)

Computational Biology

Our group uses computational methods in order to complement experimental studies into enzyme catalysis and evolution, synthetic biology and medicinal chemistry. Advanced quantum mechanical (QM) methods, including coupled-cluster, DFT and QM/MM calculations, are used to model the structure and electronic properties of a variety of systems, including novel nucleobases used in expanded genetic alphabets, enzyme reaction mechanisms and transition state structures, and how protein environments modulate transition metal reactivity. We also force field-based classical molecular dynamics (MD) simulations and enhanced sampling methods to explore the dynamical properties of DNA and RNA molecules containing non-standard nucleobases, and the free energy of interaction in enzyme/inhibitor and protein/nucleic acid complexes.

Fundamental Studies of Enzyme Catalysis and Enzyme Evolution

The molecular basis by which enzymes, particularly those that are transition metal-dependent, catalyze chemically unusual transformations are studied in a multi-disciplinary approach. The goal of current projects is to examine how metals generate substrate-based radicals, which can then undergo reactions for which there is no organic chemical precedent.

Synthetic Biology

Synthetic Biology capitalizes on advances in genomics and proteomics and new insights from chemical and physical studies into the molecular mechanisms by which biological molecules perform their cellular function. Our projects aim to understand the structure and properties of DNA and RNA containing additional nucleobases, and to develop novel reagents (endonucleases and polymerases) by which non-standard nucleobases can be manipulated. In addition, we are involved in reengineering several enzymes in order to obtain variants that can be introduced into cells and used for the synthesis of important chemicals and synthetic intermediates.

Medicinal Chemistry/Synthesis.

Small molecule chemistry together with mechanistic studies of enzymes for the development of selective inhibitors that can be used to treat (i) sarcoma and breast cancer, and (ii) bacterial infections, with a particular emphasis on Mycobacterium tuberculosis (the causative agent of tuberculosis).

CH2317 Chemical Biology III: Biosynthetic Approach to Natural Products

CHT214 Biocatalysis I: Modern Approaches to Biocatalysts

B.Sc. (Hons.), Imperial College, University of London (1980), PhD Cambridge University (1980-83).

Commonwealth Foundation (Harkness) Postdoctoral Research Fellow, Columbia University, New York (1983-1985), University Lecturer Department of Chemistry, University of Southampton (1985-1990), Assistant Professor in Chemistry, University of Florida (1990-1996), Associate Professor in Chemistry, University of Florida (1996-2003), Full Professor in Chemistry, University of Florida (2003-2012), Fellow of the American Association for the Advancement of Science (2010), Full Professor and Chair, Department of Chemistry & Chemical Biology, Indiana University Purdue University Indianapolis (2012-2015). Since 2015: Professor of Biological Chemistry, Cardiff School of Chemistry.