Influence of water and enzyme SpnF on the dynamics and energetics of the ambimodal [6+4]/[4+2] cycloaddition

Proceedings of the National Academy of Sciences of the United States of America

Volumn 115, Issue 5, 2018, Pages E848-E855

  Yang, Zhongyue ^a   Yang, Song ^a   Yu, Peiyuan ^a   Li, Yanwei ^a,b   Doubleday, Charles ^c   Park, Jiyong ^a,d   Patel, Ashay ^a,e   Jeon, Byung sun ^f,g   Russell, William K ^h   Liu, Hung wen ^f,g   Russell, David H ^h   Houk, Kendall N ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b SHANDONG UNIVERSITY   (China)

^c Och Spine at New York Presbyterian Hospitals   (United States)

^d Institute for Basic Science   (South Korea)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^g The University of Texas at Austin   (United States)

^h TEXAS A AND M UNIVERSITY   (United States)

Author keywords

Environment perturbed; Potential energy surface bifurcation; SpnF enzyme; Time resolved mechanism; Transition state sampling

Indexed keywords

ENZYME; SPNF ENZYME; UNCLASSIFIED DRUG; WATER; BACTERIAL PROTEIN; MACROLIDE; SPINOSYN A;

ARTICLE; CATALYSIS; CONFORMATIONAL TRANSITION; CYCLOADDITION; DIELS ALDER REACTION; ENERGY TRANSFER; HYDROGEN BOND; HYDROPHOBICITY; MOLECULAR DYNAMICS; PHASE TRANSITION; PRIORITY JOURNAL; QUANTUM MECHANICS; CHEMICAL MODEL; CHEMICAL PHENOMENA; CHEMISTRY; CONFORMATION; ENZYMOLOGY; KINETICS; METABOLISM; QUANTUM THEORY; SACCHAROPOLYSPORA; SOFTWARE;

BACTERIAL PROTEINS; CATALYSIS; CYCLOADDITION REACTION; HYDROGEN BONDING; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; KINETICS; MACROLIDES; MODELS, CHEMICAL; MOLECULAR CONFORMATION; MOLECULAR DYNAMICS SIMULATION; QUANTUM THEORY; SACCHAROPOLYSPORA; SOFTWARE; WATER;

EID: 85041217103     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1719368115     Document Type: Article

References (42)

1. Kim HJ, Ruszczycky MW, Choi S-H, Liu Y-N, Liu HW (2011) Enzyme-catalysed [4+2] cycloaddition is a key step in the biosynthesis of spinosyn A. Nature 473:109–112.
2. Patel A, et al. (2016) Dynamically complex [6+4] and [4+2] cycloadditions in the biosynthesis of spinosyn A. J Am Chem Soc 138:3631–3634.
3. Yu P, Patel A, Houk KN (2015) Transannular [6 + 4] and ambimodal cycloaddition in the biosynthesis of heronamide A. J Am Chem Soc 137:13518–13523.
4. Carpenter BK (1995) Dynamic matching: The cause of inversion of configuration in the [1, 3] sigmatropic migration? J Am Chem Soc 117:6336–6344.
5. Lourderaj U, Park K, Hase WL (2008) Classical trajectory simulations of post-transition state dynamics. Int Rev Phys Chem 27:361–403.
6. Diels O, Alder K (1928) Synthesen in der hydroaromatischen reihe. Justus Liebigs Ann Chem 460:98–122.
7. Nicolaou KC, Snyder SA, Montagnon T, Vassilikogiannakis G (2002) The Diels–Alder reaction in total synthesis. Angew Chem Int Ed Engl 41:1668–1698.
8. Jeon BS, Wang S-A, Ruszczycky MW, Liu HW (2017) Natural [4 + 2]-cyclases. Chem Rev 117:5367–5388.
9. Oikawa H, Tokiwano T (2004) Enzymatic catalysis of the Diels-Alder reaction in the biosynthesis of natural products. Nat Prod Rep 21:321–352.
10. Minami A, Oikawa H (2016) Recent advances of Diels-Alderases involved in natural product biosynthesis. J Antibiot (Tokyo) 69:500–506.
11. Fage CD, et al. (2015) The structure of SpnF, a standalone enzyme that catalyzes [4 + 2] cycloaddition. Nat Chem Biol 11:256–258.
12. Cheng GJ, Zhang X, Chung LW, Xu L, Wu YD (2015) Computational organic chemistry: Bridging theory and experiment in establishing the mechanisms of chemical reactions. J Am Chem Soc 137:1706–1725.
13. Houk KN, Liu F (2017) Holy grails for computational organic chemistry and biochemistry. Acc Chem Res 50:539–543.
14. Lu X, et al. (2016) QM/MM free energy simulations: Recent progress and challenges. Mol Simul 42:1056–1078.
15. Byrne MJ, et al. (2016) The catalytic mechanism of a natural Diels–Alderase revealed in molecular detail. J Am Chem Soc 138:6095–6098.
16. Kneipp K, et al. (1997) Single molecule detection using surface-enhanced Raman scattering (SERS). Phys Rev Lett 78:1667–1670.
17. Lu HP, Xun L, Xie XS (1998) Single-molecule enzymatic dynamics. Science 282: 1877–1882.
18. Ess DH, et al. (2008) Bifurcations on potential energy surfaces of organic reactions. Angew Chem Int Ed Engl 47:7592–7601.
19. Yang Z, Yu P, Houk KN (2016) Molecular dynamics of dimethyldioxirane C–H oxidation. J Am Chem Soc 138:4237–4242.
20. Nieves-Quinones Y, Singleton DA (2016) Dynamics and the regiochemistry of nitration of toluene. J Am Chem Soc 138:15167–15176.
21. Yu P, et al. (2017) Mechanisms and origins of periselectivity of the ambimodal [6 + 4] cycloadditions of tropone to dimethylfulvene. J Am Chem Soc 139:8251–8258.
22. Hong YJ, Tantillo DJ (2009) A potential energy surface bifurcation in terpene biosynthesis. Nat Chem 1:384–389.
23. Major DT, Weitman M (2012) Electrostatically guided dynamics–The root of fidelity in a promiscuous terpene synthase? J Am Chem Soc 134:19454–19462.
24. Warshel A, Levitt M (1976) Theoretical studies of enzymic reactions: Dielectric, electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme. J Mol Biol 103:227–249.
25. Senn HM, Thiel W (2009) QM/MM methods for biomolecular systems. Angew Chem Int Ed Engl 48:1198–1229.
26. Yang Z, Doubleday C, Houk KN (2015) QM/MM protocol for direct molecular dynamics of chemical reactions in solution: The water-accelerated Diels–Alder reaction. J Chem Theory Comput 11:5606–5612.
27. Medvedev MG, et al. (2017) Quantifying possible routes for SpnF-catalyzed formal Diels−Alder cycloaddition. J Am Chem Soc 139:3942–3945.
28. Noey EL, et al. (2015) Origins of stereoselectivity in evolved ketoreductases. Proc Natl Acad Sci USA 112:E7065–E7072.
29. Lin H, Truhlar DG (2007) QM/MM: What have we learned, where are we, and where do we go from here? Theor Chem Acc 117:185–199.
30. Masgrau L, Truhlar DG (2015) The importance of ensemble averaging in enzyme kinetics. Acc Chem Res 48:431–438.
31. Zheng Y, Thiel W (2017) Computational insights into an enzyme-catalyzed [4+2] cycloaddition. J Org Chem 82:13563–13571.
32. Jeon BS, et al. (2017) Investigation of the mechanism of the SpnF-catalyzed [4+2]-cycloaddition reaction in the biosynthesis of spinosyn A. Proc Natl Acad Sci USA 114: 10408–10413.
33. Blake JF, Jorgensen WL (1991) Solvent effects on a Diels–Alder reaction from computer simulations. J Am Chem Soc 113:7430–7432.
34. Gordeev EG, Ananikov VP (2015) Computational study of a model system of enzyme-mediated [4+2] cycloaddition reaction. PLoS One 10:e0119984.
35. Falzone CJ, Wright PE, Benkovic SJ (1994) Dynamics of a flexible loop in dihydrofolate reductase from Escherichia coli and its implication for catalysis. Biochemistry 33: 439–442.
36. Agarwal PK, Billeter SR, Rajagopalan PT, Benkovic SJ, Hammes-Schiffer S (2002) Network of coupled promoting motions in enzyme catalysis. Proc Natl Acad Sci USA 99:2794–2799.
37. Black K, Liu P, Xu L, Doubleday C, Houk KN (2012) Dynamics, transition states, and timing of bond formation in Diels-Alder reactions. Proc Natl Acad Sci USA 109:12860–12865.
38. Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113:6378–6396.
39. Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: Two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc 120:215–241.
40. Frisch MJ, et al. (2009) Gaussian 09 (Gaussian, Inc., Wallingford, CT).
41. Case DA, et al. (2014) Amber14 (University of California, San Francisco).
42. Truhlar DG, et al. (2002) The incorporation of quantum effects in enzyme kinetics modeling. Acc Chem Res 35:341–349.