Cooperative Institute for Research in Environmental Sciences at the University of Colorado Boulder

Shelley D. Copley

Research Interests

My lab studies the molecular evolution of enzymes and metabolic pathways. Metabolic enzymes are superb catalysts, accelerating chemical reactions by up to 20 orders of magnitude. Many, and probably all, also catalyze adventitious secondary reactions due to the highly reactive nature of their active sites. Although these “promiscuous” activities are often inefficient, they provide a repertoire of activities that can be drawn upon if conditions change and catalysis of a secondary reaction becomes important for fitness. Since most bacteria have 1000-2000 enzymes, and each enzyme probably has several promiscuous activities, bacteria can access many thousands of catalytic activities when a new enzyme is needed to enhance fitness or even to enable survival.

Current Research

Evolution of a New Enzyme by Gene Duplication and Divergence

New enzymes often evolve from promiscuous activities of previously existing enzymes by a process of gene duplication/amplification and divergence. Previous studies of this process have focused solely on mutations in the gene undergoing duplication /amplification and divergence.  We are taking a genome-wide approach to studying all of the mutations that contribute to fitness in the face of a novel evolutionary challenge.

ArgC (N-acetyl-L-g-glutamylphosphate reductase) is essential for growth of E. coli on glucose because it is required for arginine synthesis. However, a point mutation in proA allows ProA (glutamylphosphate reductase) to serve both functions, albeit poorly. We refer to this enzyme as ProA*. ProA* is the “weak-link” in metabolism; hence, cells are under strong selective pressure to increase its catalytic activity. We evolved eight lineages of a strain lacking ArgC and carrying ProA* under selection for improved synthesis of arginine (Figure 1). As expected, the region surrounding proA* amplifies to several copies. A mutation in proA* was detected only in population 3. In the other populations, we observed genomic mutations that increase arginine synthesis by either pushing or pulling material through the compromised biosynthetic pathway. This work demonstrates that evolution of a new enzyme by gene duplication and divergence is inextricably intertwined with genomic mutations that improve fitness by other mechanisms.

Promiscuity, Serendipity and Metabolic Innovation

Promiscuous enzymes can serve as the starting point for evolution of new enzyme activities. However, their evolutionary potential goes further; multiple promiscuous activities can be patched together to generate novel metabolic pathways. We call these pathways “serendipitous” because their assembly relies upon the fortuitous combination of available promiscuous activities, which can differ substantially in different organisms, or in the same organism under different environmental conditions.

We are studying the emergence of serendipitous pathways in a model system in which we have deleted a gene (pdxB) that is required for synthesis of the essential cofactor pyridoxal 5-phosphate (PLP, a.k.a. vitamin B6). We have succeeded in restoring robust growth of ∆pdxB E. coli within as few as 150 generations by a novel four-step serendipitous pathway.  Each step of the serendipitous pathway is catalyzed by a promiscuous enzyme that normally serves another function. This work demonstrates the potential for evolution of novel metabolic pathways that resides within the proteome of a bacterium.

We discovered that a strikingly different suite of mutations was found when the same strain was evolved under different environmental conditions, suggesting that either a different solution to the evolutionary challenge was found, or that the same solution emerged but by a different mechanism. Current work addresses how PLP synthesis can be restored in strains evolved under other environmental conditions.



a series of 8 graphs showing growth rate changes by strain, conditions

Changes in growth rate and proA* copy number during evolution of ∆argC proAE. coli  on glucose + proline to select for improved synthesis of arginine. The parental strain also carried a previously identified promoter mutation. Ch. = chamber in the turbidostat used for the evolution experiment

chemical synthesis pathyways

A serendipitous pathway (pink) that restores growth of a strain of E. coli that lacks an essential gene (PdxB) in the PLP synthesis pathway (cyan). Red denotes promiscuous functions of enzymes that normally serve other functions.   

View Publications

  • Mikkonen, A, K Ylaranta, M Tiirola, LAL Dutra, P Salmi, M Romantschuk, S Copley, J Ikaheimo and A Sinkkonen (2018), Successful aerobic bioremediation of groundwater contaminated with higher chlorinated phenols by indigenous degrader bacteria. Water Res. Version: 1 138 118-128, issn: 0043-1354, ids: GF2DA, doi: 10.1016/j.watres.2018.03.033, PubMed ID: 29574199
  • Kristofich, J, AB Morgenthaler, WR Kinney, CC Ebmeier, DJ Snyder, WM Old, VS Cooper and SD Copley (2018), Synonymous mutations make dramatic contributions to fitness when growth is limited by a weak-link enzyme. PLoS Genet. Version: 1 14 (8) , Art. No. e1007615, issn: 1553-7404, ids: GS2OB, doi: 10.1371/journal.pgen.1007615, PubMed ID: 30148850
  • Flood, JJ; Copley, SD (2018), Genome-Wide Analysis of Transcriptional Changes and Genes That Contribute to Fitness during Degradation of the Anthropogenic Pollutant Pentachlorophenol by Sphingobium chlorophenolicum. Version: 1 MSYSTEMS 3 (6) , Art. No. e00275-18, issn: 2379-5077, doi: 10.1128/mSystems.00275-18, PubMed ID: 30505947
  • Copley, SD (2017), Shining a light on enzyme promiscuity. Curr. Opin. Struct. Biol. Version: 1 47 167-175, issn: 0959-440X, ids: FR9SP, doi: 10.1016/j.sbi.2017.11.001, PubMed ID: 29169066
  • Kershner, JP, SY McLoughlin, J Kim, A Morgenthaler, CC Ebmeier, WM Old and SD Copley (2016), A Synonymous Mutation Upstream of the Gene Encoding a Weak-Link Enzyme Causes an Ultrasensitive Response in Growth Rate. J. Bacteriol. Version: 1 198 (20) 2853-2863, issn: 0021-9193, ids: DX4JQ, doi: 10.1128/JB.00262-16, PubMed ID: 27501982
  • Thiaville, JJ, J Flood, S Yurgel, L Prunetti, M Elbadawi-Sidhu, G Hutinet, F Forouhar, XS Zhang, V Ganesan, P Reddy, O Fiehn, JA Gerlt, JF Hunt, SD Copley and V de Crecy-Lagard (2016), Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite. ACS Chem. Biol. Version: 1 11 (8) 2304-2311, issn: 1554-8929, ids: DT9UL, doi: 10.1021/acschembio.6b00279, PubMed ID: 27294475
  • Khanal, A, SY McLoughlin, JP Kershner and SD Copley (2015), Differential Effects of a Mutation on the Normal and Promiscuous Activities of Orthologs: Implications for Natural and Directed Evolution. Mol. Biol. Evol. Version: 1 32 (1) 100-108, issn: 0737-4038, ids: CC0TR, doi: 10.1093/molbev/msu271, PubMed ID: 25246702
  • Copley, SD (2015), An evolutionary biochemists perspective on promiscuity. Trends Biochem.Sci. Version: 1 40 (2) 72-78, issn: 0968-0004, ids: CB4GR, doi: 10.1016/j.tibs.2014.12.004, PubMed ID: 25573004
  • Kim, J, AM Webb, JP Kershner, S Blaskowski and SD Copley (2014), A versatile and highly efficient method for scarless genome editing in Escherichia coli and Salmonella enterica. BMC Biotechnol. Version: 1 14 , Art. No. 84, issn: 1472-6750, ids: AR6FF, doi: 10.1186/1472-6750-14-84, PubMed ID: 25255806
  • Copley, SD (2014), An evolutionary perspective on protein moonlighting. Biochem. Soc. Trans. Version: 1 42 1684-1691, issn: 0300-5127, ids: AU2DT, doi: 10.1042/BST20140245, PubMed ID: 25399590
  • Rokicki, J, D Knox, RD Dowell and SD Copley (2014), CodaChrome: a tool for the visualization of proteome conservation across all fully sequenced bacterial genomes. BMC Genomics Version: 1 15 , Art. No. 65, issn: 1471-2164, ids: AA5DG, doi: 10.1186/1471-2164-15-65, PubMed ID: 24460813
  • Rudolph, J, AH Erbse, LS Behlen and SD Copley (2014), A Radical Intermediate in the Conversion of Pentachlorophenol to Tetrachlorohydroquinone by Sphingobium chlorophenolicum. Biochemistry Version: 1 53 (41) 6539-6549, issn: 0006-2960, ids: AR5RC, doi: 10.1021/bi5010427, PubMed ID: 25238136
  • Novikov, Y and SD Copley (2013), Reactivity landscape of pyruvate under simulated hydrothermal vent conditions. Proc. Natl. Acad. Sci. U. S. A. Version: 1 110 (33) 13283-13288, issn: 0027-8424, ids: 200LA, doi: 10.1073/pnas.1304923110, PubMed ID: 23872841
  • Kim, J and SD Copley (2013), The Orphan Protein Bis-gamma-glutamylcystine Reductase Joins the Pyridine Nucleotide Disulfide Reductase Family. Biochemistry Version: 1 52 (17) 2905-2913, issn: 0006-2960, ids: 136AZ, doi: 10.1021/bi4003343, PubMed ID: 23560638
  • Yadid, I, J Rudolph, K Hlouchova and SD Copley (2013), Sequestration of a highly reactive intermediate in an evolving pathway for degradation of pentachlorophenol. Proc. Natl. Acad. Sci. U. S. A. Version: 1 110 (24) E2182-E2190, issn: 0027-8424, ids: 171LM, doi: 10.1073/pnas.1214052110, PubMed ID: 23676275
  • Copley, SD, J Rokicki, P Turner, H Daligault, M Nolan and M Land (2012), The Whole Genome Sequence of Sphingobium chlorophenolicum L-1: Insights into the Evolution of the Pentachlorophenol Degradation Pathway. Genome Biol. Evol. Version: 1 4 (2) 184-198, issn: 1759-6653, ids: 914VJ, doi: 10.1093/gbe/evr137, PubMed ID: 22179583
  • Copley, SD (2012), Toward a Systems Biology Perspective on Enzyme Evolution. J. Biol. Chem. Version: 1 287 (1) 3-10, issn: 0021-9258, ids: 870PW, doi: 10.1074/jbc.R111.254714, PubMed ID: 22069330
  • Kim, J and SD Copley (2012), Inhibitory cross-talk upon introduction of a new metabolic pathway into an existing metabolic network. Proc. Natl. Acad. Sci. U. S. A. Version: 1 109 (42) E2856-E2864, issn: 0027-8424, ids: 029SK, doi: 10.1073/pnas.1208509109, PubMed ID: 22984162
  • Hlouchova, K, J Rudolph, JMH Pietari, LS Behlen and SD Copley (2012), Pentachlorophenol Hydroxylase, a Poorly Functioning Enzyme Required for Degradation of Pentachlorophenol by Sphingobium chlorophenolicum. Biochemistry Version: 1 51 (18) 3848-3860, issn: 0006-2960, ids: 936ZG, doi: 10.1021/bi300261p, PubMed ID: 22482720
  • Copley, SD (2012), Moonlighting is mainstream: Paradigm adjustment required. Bioessays Version: 1 34 (7) 578-588, issn: 0265-9247, ids: 958KG, doi: 10.1002/bies.201100191, PubMed ID: 22696112
  • Chumachenko, N, Y Novikov, RK Shoemaker and SD Copley (2011), A Dimethyl Ketal-Protected Benzoin-Based Linker Suitable for Photolytic Release of Unprotected Peptides. J. Org. Chem. Version: 1 76 (22) 9409-9416, issn: 0022-3263, ids: 844NN, doi: 10.1021/jo2017263, PubMed ID: 21950361
  • Novikov, Y, SD Copley and BE Eaton (2011), A simple route for synthesis of 4-phospho-D-erythronate. Tetrahedron Lett. Version: 1 52 (16) 1913-1915, issn: 0040-4039, ids: 765YV, doi: 10.1016/j.tetlet.2011.02.045, PubMed ID: 22200980
  • Kim, JH, JP Kershner, Y Novikov, RK Shoemaker and SD Copley (2010), Three serendipitous pathways in E. coli can bypass a block in pyridoxal-5 -phosphate synthesis. Mol. Syst. Biol. Version: 1 6 , Art. No. 436, issn: 1744-4292, ids: 691GI, doi: 10.1038/msb.2010.88, PubMed ID: 21119630
  • Rudolph, J, J Kim and SD Copley (2010), Multiple Turnovers of the Nicotino-Enzyme PdxB Require alpha-Keto Acids as Cosubstrates. Biochemistry Version: 1 49 (43) 9249-9255, issn: 0006-2960, ids: 670GL, doi: 10.1021/bi101291d, PubMed ID: 20831184
  • Copley, SD (2010), Evolution and the Enzyme. Version: 1 COMPREHENSIVE NATURAL PRODUCTS II: CHEMISTRY AND BIOLOGY, VOL 8: ENZYMES AND ENZYME MECHANISMS 9-46, Ed. Mander, L; Liu, HW, ids: BA5BC, isbn: 978-0-08-045382-8
  • Copley, SD (2009), Evolution of efficient pathways for degradation of anthropogenic chemicals. Nat. Chem. Biol. Version: 1 5 (8) 560-567, issn: 1552-4450, ids: 473LV, doi: 10.1038/nchembio.197, PubMed ID: 19620997
  • Hamady, M, J Widmann, SD Copley and R Knight (2008), MotifCluster: an interactive online tool for clustering and visualizing sequences using shared motifs. Genome Biol. Version: 1 9 (8) , Art. No. R128, issn: 1474-760X, ids: 355IA, doi: 10.1186/gb-2008-9-8-r128, PubMed ID: 18706079
  • Warner, JR, LS Behlen and SD Copley (2008), A trade-off between catalytic power and substrate inhibition in TCHQ dehalogenase. Biochemistry Version: 1 47 (10) 3258-3265, issn: 0006-2960, ids: 270NG, doi: 10.1021/bi702431n, PubMed ID: 18275157
  • McLoughlin, SY and SD Copley (2008), A compromise required by gene sharing enables survival: Implications for evolution of new enzyme activities. Proc. Natl. Acad. Sci. U. S. A. Version: 1 105 (36) 13497-13502, issn: 0027-8424, ids: 349AR, doi: 10.1073/pnas.0804804105, PubMed ID: 18757760
  • Warner, JR and SD Copley (2007), Pre-steady-state kinetic studies of the reductive dehalogenation catalyzed by tetrachlorohydroquinone dehalogenase. Biochemistry Version: 1 46 (45) 13211-13222, issn: 0006-2960, ids: 228XT, doi: 10.1021/bi701069n, PubMed ID: 17956123
  • Warner, JR and SD Copley (2007), Mechanism of the severe inhibition of tetrachlorohydroquinone dehalogenase by its aromatic substrates. Biochemistry Version: 1 46 (14) 4438-4447, issn: 0006-2960, ids: 152OD, doi: 10.1021/bi0620104, PubMed ID: 17355122
  • Copley, SD, E Smith and HJ Morowitz (2007), The origin of the RNA world: Co-evolution of genes and metabolism. Bioorganic Chem. Version: 1 35 (6) 430-443, issn: 0045-2068, ids: 237GV, doi: 10.1016/j.bioorg.2007.08.001, PubMed ID: 17897696
  • Kim, J and SD Copley (2007), Why metabolic enzymes are essential or nonessential for growth of Escherichia coli k12 on glucose. Biochemistry Version: 1 46 (44) 12501-12511, issn: 0006-2960, ids: 226FA, doi: 10.1021/bi7014629, PubMed ID: 17935357
  • Warner, JR, SL Lawson and SD Copley (2005), A mechanistic investigation of the thiol-disulfide exchange step in the reductive dehalogenation catalyzed by tetrachlorohydroquinone dehalogenase. Biochemistry Version: 1 44 (30) 10360-10368, issn: 0006-2960, ids: 950TG, doi: 10.1021/bi050666b, PubMed ID: 16042413
  • Copley, SD, E Smith and HJ Morowitz (2005), A mechanism for the association of amino acids with their codons and the origin of the genetic code. Proc. Natl. Acad. Sci. U. S. A. Version: 1 102 (12) 4442-4447, issn: 0027-8424, ids: 909IY, doi: 10.1073/pnas.0501049102, PubMed ID: 15764708
  • Cleland, CE and SD Copley (2005), The possibility of alternative microbial life on Earth. Int. J. Astrobiol. Version: 1 4 (4-Mar) 165-173, issn: 1473-5504, ids: V28BK, doi: 10.1017/S147355040500279X
  • Dai, MH, S Ziesman, T Ratcliffe, RT Gill and SD Copley (2005), Visualization of protoplast fusion and quantitation of recombination in fused protoplasts of auxotrophic strains of Escherichia coli. Metab. Eng. Version: 1 7 (1) 45-52, issn: 1096-7176, ids: 904LI, doi: 10.1016/j.ymben.2004.09.002, PubMed ID: 15974564
  • Dai, MH and SD Copley (2004), Genome shuffling improves degradation of the anthropogenic pesticide pentachlorophenol by Sphingobium chlorophenolicum ATCC 39723. Appl. Environ. Microbiol. Version: 1 70 (4) 2391-2397, issn: 0099-2240, ids: 811SS, doi: 10.1128/AEM.70.4.2391-2397.2004, PubMed ID: 15066836
  • Copley, SD, WRP Novak and PC Babbitt (2004), Divergence of function in the thioredoxin fold suprafamily: Evidence for evolution of peroxiredoxins from a thioredoxin-like ancestor. Biochemistry Version: 1 43 (44) 13981-13995, issn: 0006-2960, ids: 868UV, doi: 10.1021/bi048947r, PubMed ID: 15518547
  • Dai, MH, JB Rogers, JR Warner and SD Copley (2003), A previously unrecognized step in pentachlorophenol degradation in Sphingobium chlorophenolicum is catalyzed by tetrachlorobenzoquinone reductase (PcpD). J. Bacteriol. Version: 1 185 (1) 302-310, issn: 0021-9193, ids: 629LJ, doi: 10.1128/JB.185.1.302-310.2003, PubMed ID: 12486067
  • Copley, SD (2003), Enzymes with extra talents: moonlighting functions and catalytic promiscuity. Curr. Opin. Chem. Biol. Version: 1 7 (2) 265-272, issn: 1367-5931, ids: 676FB, doi: 10.1016/S1367-5931(03)00032-2, PubMed ID: 12714060
  • Kiefer, PM, DL McCarthy and SD Copley (2002), The reaction catalyzed by tetrachlorohydroquinone dehalogenase does not involve nucleophilic aromatic substitution. Biochemistry Version: 1 41 (4) 1308-1314, issn: 0006-2960, ids: 517LM, doi: 10.1021/bi0117495, PubMed ID: 11802731
  • Kiefer, PM and SD Copley (2002), Characterization of the initial steps in the reductive dehalogenation catalyzed by tetrachlorohydroquinone dehalogenase. Biochemistry Version: 1 41 (4) 1315-1322, issn: 0006-2960, ids: 517LM, doi: 10.1021/bi0117504, PubMed ID: 11802732
  • Copley, SD, K Anandarajah and PJ Kiefer (2001), A tale of two enzymes: tetrachlorohydroquinone dehalogenase and maleylacetoacetate isomerase. Chem.-Biol. Interact. Version: 1 International Conference on Glutathione Transferases 133 (3-Jan) 200-203, UPPSALA, SWEDEN, MAY 19-23, 2000, issn: 0009-2797, ids: 424QY
  • Anandarajah, K, PM Kiefer, BS Donohoe and SD Copley (2000), Recruitment of a double bond isomerase to serve as a reductive dehalogenase during biodegradation of pentachlorophenol. Biochemistry Version: 1 39 (18) 5303-5311, issn: 0006-2960, ids: 312PD, doi: 10.1021/bi9923813, PubMed ID: 10820000
  • Fall, R and SD Copley (2000), Bacterial sources and sinks of isoprene, a reactive atmospheric hydrocarbon. Environ. Microbiol. Version: 1 2 (2) 123-130, issn: 1462-2912, ids: 315HE, doi: 10.1046/j.1462-2920.2000.00095.x, PubMed ID: 11220299
  • Copley, SD (2000), Evolution of a metabolic pathway for degradation of a toxic xenobiotic: the patchwork approach. Trends Biochem.Sci. Version: 1 25 (6) 261-265, issn: 0968-0004, ids: 322UU, doi: 10.1016/S0968-0004(00)01562-0, PubMed ID: 10838562
  • Xu, L, K Resing, SL Lawson, PC Babbitt and SD Copley (1999), Evidence that pcpA encodes 2,6-dichlorohydroquinone dioxygenase, the ring cleavage enzyme required for pentachlorophenol degradation in Sphingomonas chlorophenolica strain ATCC 39723. Biochemistry Version: 1 38 (24) 7659-7669, issn: 0006-2960, ids: 208XB, doi: 10.1021/bi990103y, PubMed ID: 10387005
  • Copley, SD (1998), Microbial dehalogenases: enzymes recruited to convert xenobiotic substrates. Curr. Opin. Chem. Biol. Version: 1 2 (5) 613-617, issn: 1367-5931, ids: 135YT, doi: 10.1016/S1367-5931(98)80092-6, PubMed ID: 9818187
  • Copley, SD (1997), Diverse mechanistic approaches to difficult chemical transformations: Microbial dehalogenation of chlorinated aromatic compounds. Chem. Biol. Version: 1 4 (3) 169-174, issn: 1074-5521, ids: WV743, doi: 10.1016/S1074-5521(97)90285-4, PubMed ID: 9115409
  • McCarthy, DL, AA Claude and SD Copley (1997), In vivo levels of chlorinated hydroquinones in a pentachlorophenol-degrading bacterium. Appl. Environ. Microbiol. Version: 1 63 (5) 1883-1888, issn: 0099-2240, ids: WX361, PubMed ID: 9143119
  • McCarthy, DL, DF Louie and SD Copley (1997), Identification of a covalent intermediate between glutathione and cysteine13 formed during catalysis by tetrachlorohydroquinone dehalogenase. J. Am. Chem. Soc. Version: 1 119 (46) 11337-11338, issn: 0002-7863, ids: YG901, doi: 10.1021/ja9726365
  • McCarthy, DL, S Navarrete, WS Willett, PC Babbitt and SD Copley (1996), Exploration of the relationship between tetrachlorohydroquinone dehalogenase and the glutathione S-transferase superfamily. Biochemistry Version: 1 35 (46) 14634-14642, issn: 0006-2960, ids: VU224, doi: 10.1021/bi961730f, PubMed ID: 8931562
  • Willett, WS and SD Copley (1996), Identification and localization of a stable sulfenic acid in peroxide-treated tetrachlorohydroquinone dehalogenase using electrospray mass spectrometry. Chem. Biol. Version: 1 3 (10) 851-857, issn: 1074-5521, ids: VR145, PubMed ID: 8939704
  • CROOKS, GP, L XU, RM BARKLEY and SD COPLEY (1995), EXPLORATION OF POSSIBLE MECHANISMS FOR 4-CHLOROBENZOYL COA DEHALOGENASE - EVIDENCE FOR AN ARYL-ENZYME INTERMEDIATE. J. Am. Chem. Soc. Version: 1 117 (44) 10791-10798, issn: 0002-7863, ids: TD410, doi: 10.1021/ja00149a001
  • CROOKS, GP and SD COPLEY (1994), PURIFICATION AND CHARACTERIZATION OF 4-CHLOROBENZOYL COA DEHALOGENASE FROM ARTHROBACTER SP STRAIN 4-CB1. Biochemistry Version: 1 33 (38) 11645-11649, issn: 0006-2960, ids: PJ293, doi: 10.1021/bi00204a028, PubMed ID: 7918379
  • CROOKS, GP and SD COPLEY (1993), A SURPRISING EFFECT OF LEAVING GROUP ON THE NUCLEOPHILIC AROMATIC-SUBSTITUTION REACTION CATALYZED BY 4-CHLOROBENZOYL-COA DEHALOGENASE. J. Am. Chem. Soc. Version: 1 115 (14) 6422-6423, issn: 0002-7863, ids: LT173, doi: 10.1021/ja00067a072
  • COPLEY, SD and GP CROOKS (1992), ENZYMATIC DEHALOGENATION OF 4-CHLOROBENZOYL COENZYME-A IN ACINETOBACTER SP STRAIN 4-CB1. Appl. Environ. Microbiol. Version: 1 58 (4) 1385-1387, issn: 0099-2240, ids: HM121, PubMed ID: 16348702
  • COPLEY, SD, E FRANK, WM KIRSCH and TH KOCH (1992), DETECTION AND POSSIBLE ORIGINS OF AMINOMALONIC ACID IN PROTEIN HYDROLYSATES. Anal. Biochem. Version: 1 201 (1) 152-157, issn: 0003-2697, ids: HE336, doi: 10.1016/0003-2697(92)90188-D, PubMed ID: 1621954
  • COPLEY, SD and JR KNOWLES (1987), THE CONFORMATIONAL EQUILIBRIUM OF CHORISMATE IN SOLUTION - IMPLICATIONS FOR THE MECHANISM OF THE NONENZYMATIC AND THE ENZYME-CATALYZED REARRANGEMENT OF CHORISMATE TO PREPHENATE. J. Am. Chem. Soc. Version: 1 109 (16) 5008-5013, issn: 0002-7863, ids: J5208, doi: 10.1021/ja00250a040
  • GUILFORD, WJ, SD COPLEY and JR KNOWLES (1987), ON THE MECHANISM OF THE CHORISMATE MUTASE REACTION. J. Am. Chem. Soc. Version: 1 109 (16) 5013-5019, issn: 0002-7863, ids: J5208, doi: 10.1021/ja00250a041
  • COPLEY, SD and JR KNOWLES (1985), THE UNCATALYZED CLAISEN REARRANGEMENT OF CHORISMATE TO PREPHENATE PREFERS A TRANSITION-STATE OF CHAIRLIKE GEOMETRY. J. Am. Chem. Soc. Version: 1 107 (18) 5306-5308, issn: 0002-7863, ids: AQE67, doi: 10.1021/ja00304a064
  • GRIMSHAW, CE, SG SOGO, SD COPLEY and JR KNOWLES (1984), SYNTHESIS OF STEREOSELECTIVELY LABELED [9-H-2,H-3] CHORISMATE AND THE STEREOCHEMICAL COURSE OF "5-ENOLPYRUVOYLSHIKIMATE-3-PHOSPHATE SYNTHETASE. J. Am. Chem. Soc. Version: 1 106 (9) 2699-2700, issn: 0002-7863, ids: SP772, doi: 10.1021/ja00321a037
  • KOVACHY, RJ, SD COPLEY and RH ALLEN (1983), RECOGNITION, ISOLATION, AND CHARACTERIZATION OF RAT-LIVER D-METHYLMALONYL COENZYME-A HYDROLASE. J. Biol. Chem. Version: 1 258 (18) 1415-1421, issn: 0021-9258, ids: RH492, PubMed ID: 6885824