异戊烯基转移酶NphB催化合成大麻萜酚机制的理论计算研究

[1] YANG Y X, WANG J X, WANG Q, et al. New chromane and chromene meroterpenoids from flowers of Rhododendron rubiginosum Franch. var. rubiginosum[J]. Fitoterapia, 2018, 127: 396-401.
[2] HAPPYANA N, AGNOLET S, MUNTENDAM R, et al. Analysis of cannabinoids in lasermicrodissected trichomes of medicinal Cannabis sativa using LCMS and cryogenic NMR[J]. Phytochemistry, 2013, 87: 51-59.
[3] BONINI S A, PREMOLI M, TAMBARO S, et al. Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history[J]. Journal of Ethnopharmacology, 2018, 227: 300-315.
[4] LI H L. An archaeological and historical account of cannabis in China[J]. Economic Botany, 1974, 28(4): 437-448.
[5] TOUW M. The religious and medicinal uses of Cannabis in China, India and Tibet[J]. Journal of Psychoactive Drugs, 1981, 13(1): 23-34.
[6] PILUZZA G, DELOGU G, CABRAS A, et al. Differentiation between fiber and drug types of hemp (Cannabis sativa L.) from a collection of wild and domesticated accessions[J]. Genetic Resources and Crop Evolution, 2013, 60: 2331-2342.
[7] GROTENHERMEN F. The toxicology of cannabis and cannabis prohibition[J]. Chemistry & Biodiversity, 2007, 4(8): 1744-1769.
[8] GAONI Y, MECHOULAM R. Isolation, structure, and partial synthesis of an active constituent of hashish[J]. Journal of the American Chemical Society, 1964, 86(8): 1646-1647.
[9] GERARD C, MOLLEREAU C, VASSART G, et al. Nucleotide sequence of a human cannabinoid receptor cDNA.[J]. Nucleic Acids Research, 1990, 18(23): 7142.
[10] MUNRO S, THOMAS K L, ABU-SHAAR M. Molecular characterization of a peripheral receptor for cannabinoids[J]. Nature, 1993, 365(6441): 61-65.
[11] ZOU S, KUMAR U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system[J]. International Journal of Molecular Sciences, 2018, 19(3): 833-855.
[12] DEVANE W A, HANUŠ L, BREUER A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor[J]. Science, 1992, 258(5090): 1946-1949.
[13] DI MARZO V, FONTANA A, CADAS H, et al. Formation and inactivation of endogenous cannabinoid anandamide in central neurons[J]. Nature, 1994, 372(6507): 686-691.
[14] PERTWEE R G. Cannabinoid pharmacology: the first 66 years[J]. British Journal of Pharmacology, 2006, 147(S1): S163-S171.
[15] EDERY H, GRUNFELD Y, BEN-ZVI Z, et al. Structural requirements for cannabinoid activity [J]. Annals of the New York Academy of Sciences, 1971, 191(1): 40-53.
[16] DUGGAN P J. The chemistry of cannabis and cannabinoids[J]. Australian Journal of Chemistry, 2021, 74(6): 369-387.
[17] ROMERO P, PERIS A, VERGARA K, et al. Comprehending and improving cannabis specialized metabolism in the systems biology era[J]. Plant Science, 2020, 298: 110571-110589.
[18] GÜLCK T, MØLLER B L. Phytocannabinoids: origins and biosynthesis[J]. Trends in Plant Science, 2020, 25(10): 985-1004.
[19] HANUŠ L O, MEYER S M, MUÑOZ E, et al. Phytocannabinoids: a unified critical inventory[J]. Natural Product Reports, 2016, 33(12): 1357-1392.
[20] ELSOHLY M A, SLADE D. Chemical constituents of marijuana: the complex mixture of natural cannabinoids[J]. Life Sciences, 2005, 78(5): 539-548.
[21] LINCIANO P, CITTI C, LUONGO L, et al. Isolation of a high-affinity cannabinoid for the human CB1 receptor from a medicinal Cannabis sativa variety: Δ9-tetrahydrocannabutol, the butyl homologue of Δ9-tetrahydrocannabinol[J]. Journal of Natural Products, 2019, 83(1): 88-98.
[22] STOUT J M, BOUBAKIR Z, AMBROSE S J, et al. The hexanoyl-CoA precursor for cannabinoid biosynthesis is formed by an acyl-activating enzyme in Cannabis sativa trichomes[J]. The Plant Journal, 2012, 71(3): 353-365.
[23] GAGNE S J, STOUT J M, LIU E, et al. Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides[J]. Proceedings of the National Academy of Sciences, 2012, 109(31): 12811-12816.
[24] FELLERMEIER M, EISENREICH W, BACHER A, et al. Biosynthesis of cannabinoids: Incorporation experiments with 13C-labeled glucoses[J]. European Journal of Biochemistry, 2001, 268(6): 1596-1604.
[25] FELLERMEIER M, ZENK M H. Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol[J]. FEBS Letters, 1998, 427(2): 283-285.
[26] LIM K J, LIM Y P, HARTONO Y D, et al. Biosynthesis of nature-inspired unnatural cannabinoids[J]. Molecules, 2021, 26(10): 2914-2943.
[27] TAURA F, SIRIKANTARAMAS S, SHOYAMA Y, et al. Cannabidiolic-acid synthase, the chemotype-determining enzyme in the fiber-type Cannabis sativa[J]. FEBS Letters, 2007, 581 (16): 2929-2934.
[28] MORENO-SANZ G. Can you pass the acid test? critical review and novel therapeutic perspectives of Δ9-tetrahydrocannabinolic acid A[J]. Cannabis and Cannabinoid Research, 2016, 1(1): 124-130.
[29] THAKUR G A, DUCLOS JR R I, MAKRIYANNIS A. Natural cannabinoids: templates for drug discovery[J]. Life Sciences, 2005, 78(5): 454-466.
[30] PERTWEE R. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin[J]. British Journal of Pharmacology, 2008, 153(2): 199-215.
[31] FEINBERG I, JONES R, WALKER J, et al. Effeets of marijuana extract and tetrahydrocannabinol on electroencephalographic sleep patterns[J]. Clinical Pharmacology & Therapeutics, 1976, 19(6): 782-794.
[32] HIPPALGAONKAR K, GUL W, ELSOHLY M A, et al. Enhanced solubility, stability, and transcorneal permeability of delta-8-tetrahydrocannabinol in the presence of cyclodextrins[J]. Aaps Pharmscitech, 2011, 12: 723-731.
[33] CASCIO M G, ZAMBERLETTI E, MARINI P, et al. The phytocannabinoid, Δ9-tetrahydrocannabivarin, can act through 5-HT1A receptors to produce antipsychotic effects[J]. British Journal of Pharmacology, 2015, 172(5): 1305-1318.
[34] JADOON K A, RATCLIFFE S H, BARRETT D A, et al. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study[J]. Diabetes Care, 2016, 39(10): 1777-1786.
[35] NADAL X, DEL RÍO C, CASANO S, et al. Tetrahydrocannabinolic acid is a potent PPAR𝛾 agonist with neuroprotective activity[J]. British Journal of Pharmacology, 2017, 174(23): 4263-4276.
[36] IBEAS BIH C, CHEN T, NUNN A V, et al. Molecular targets of cannabidiol in neurological disorders[J]. Neurotherapeutics, 2015, 12: 699-730.
[37] BUCHTOVA T, LUKAC D, SKROTT Z, et al. Drug–drug interactions of cannabidiol with standard-of-care chemotherapeutics[J]. International Journal of Molecular Sciences, 2023, 24(3): 2885-2910.
[38] RUSSO E B, MARCU J. Cannabis pharmacology: the usual suspects and a few promising leads[J]. Advances in Pharmacology, 2017, 80: 67-134.
[39] MALINOWSKA B, BARANOWSKA-KUCZKO M, KICMAN A, et al. Opportunities, challenges and pitfalls of using cannabidiol as an adjuvant drug in COVID-19[J]. International Journal of Molecular Sciences, 2021, 22(4): 1986-2027.
[40] NGUYEN L C, YANG D, NICOLAESCU V, et al. Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses[J]. Science Advances, 2022, 8(8): 6110-6127.
[41] ROCK E M, LIMEBEER C L, PARKER L A. Effect of cannabidiolic acid and Δ9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain[J]. Psychopharmacology, 2018, 235: 3259-3271.
[42] CLUNY N L, NAYLOR R J, WHITTLE B A, et al. The effects of cannabidiolic acid and cannabidiol on contractility of the gastrointestinal tract of Suncus murinus[J]. Archives of Pharmacal Research, 2011, 34: 1509-1517.
[43] PERTWEE R G, ROCK E M, GUENTHER K, et al. Cannabidiolic acid methyl ester, a stable synthetic analogue of cannabidiolic acid, can produce 5-HT1A receptor-mediated suppression of nausea and anxiety in rats[J]. British Journal of Pharmacology, 2018, 175(1): 100-112.
[44] POLLASTRO F, TAGLIALATELA-SCAFATI O, ALLARA M, et al. Bioactive prenylogous cannabinoid from fiber hemp (Cannabis sativa)[J]. Journal of Natural Products, 2011, 74(9): 2019-2022.
[45] BRIERLEY D I, SAMUELS J, DUNCAN M, et al. A cannabigerol-rich Cannabis sativa extract, devoid offf 9-tetrahydrocannabinol, elicits hyperphagia in rats[J]. Behavioural Pharmacology, 2017, 28(4): 280-284.
[46] CASCIO M G, GAUSON L A, STEVENSON L A, et al. Evidence that the plant cannabinoid cannabigerol is a highly potent 𝛼2-adrenoceptor agonist and moderately potent 5-HT1A receptor antagonist[J]. British Journal of Pharmacology, 2010, 159(1): 129-141.
[47] PAGANO E, MONTANARO V, DI GIROLAMO A, et al. Effect of non-psychotropic plantderived cannabinoids on bladder contractility: focus on cannabigerol[J]. Natural Product Communications, 2015, 10(6): 1009-1012.
[48] SMERIGLIO A, GIOFRÈ S V, GALATI E M, et al. Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol[J]. Fitoterapia, 2018, 127: 101-108.
[49] DE PETROCELLIS L, VELLANI V, SCHIANO-MORIELLO A, et al. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8[J]. Journal of Pharmacology and Experimental Therapeutics, 2008, 325(3): 1007-1015.
[50] ROMANO B, BORRELLI F, FASOLINO I, et al. The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis[J]. British Journal of Pharmacology, 2013, 169(1): 213-229.
[51] SHINJYO N, DI MARZO V. The effect of cannabichromene on adult neural stem/progenitor cells[J]. Neurochemistry International, 2013, 63(5): 432-437.
[52] RHEE M H, VOGEL Z, BARG J, et al. Cannabinol derivatives: binding to cannabinoid receptors and inhibition of adenylylcyclase[J]. Journal of Medicinal Chemistry, 1997, 40(20): 3228-3233.
[53] WONG H, CAIRNS B E. Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain[J]. Archives of Oral Biology, 2019, 104: 33-39.
[54] SALAMI S A, MARTINELLI F, GIOVINO A, et al. It is our turn to get cannabis high: Put cannabinoids in food and health baskets[J]. Molecules, 2020, 25(18): 4036-4059.
[55] BERLACH D M, SHIR Y, WARE M A. Experience with the synthetic cannabinoid nabilone in chronic noncancer pain[J]. Pain Medicine, 2006, 7(1): 25-29.
[56] ABU-SAWWA R, STEHLING C. Epidiolex (cannabidiol) primer: frequently asked questions for patients and caregivers[J]. The Journal of Pediatric Pharmacology and Therapeutics, 2020, 25(1): 75-77.
[57] AIZPURUA-OLAIZOLA O, SOYDANER U, ÖZTÜRK E, et al. Evolution of the cannabinoid and terpene content during the growth of Cannabis sativa plants from different chemotypes[J]. Journal of Natural Products, 2016, 79(2): 324-331.
[58] MARTINEZ A S, LANARIDI O, STAGEL K, et al. Extraction techniques for bioactive compounds of cannabis[J]. Natural Product Reports, 2023, 40: 676-717.
[59] WILKINSON S M, PRICE J, KASSIOU M. Improved accessibility to the desoxy analogues of Δ9-tetrahydrocannabinol and cannabidiol[J]. Tetrahedron Letters, 2013, 54(1): 52-54.
[60] MECHOULAM R, BEN-ZVI Z. Carboxylation of resorcinols with methylmagnesium carbonate. Synthesis of cannabinoid acids[J]. Journal of the Chemical Society D: Chemical Communications, 1969, 7: 343-344.
[61] NGUYEN G N, JORDAN E N, KAYSER O. Synthetic strategies for rare cannabinoids derived from Cannabis sativa[J]. Journal of Natural Products, 2022, 85(6): 1555-1568.
[62] BLATT-JANMAAT K, QU Y. The biochemistry of phytocannabinoids and metabolic engineering of their production in heterologous systems[J]. International Journal of Molecular Sciences, 2021, 22(5): 2454-2472.
[63] KUZUYAMA T, NOEL J P, RICHARD S B. Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products[J]. Nature, 2005, 435(7044): 983-987.
[64] BONITZ T, ALVA V, SALEH O, et al. Evolutionary relationships of microbial aromatic prenyltransferases[J]. PloS One, 2011, 6(11): 27336-27343.
[65] JOHNSON B P, SCULL E M, DIMAS D A, et al. Acceptor substrate determines donor specificity of an aromatic prenyltransferase: expanding the biocatalytic potential of NphB[J]. Applied Microbiology and Biotechnology, 2020, 104: 4383-4395.
[66] TSUTSUMI H, URANO N, KATSUYAMA Y, et al. Enzymatic synthesis of non-natural flavonoids by combining geranyl pyrophosphate C6-methyltransferase and aromatic prenyltransferase[J]. Bioscience, Biotechnology, and Biochemistry, 2022, 86(9): 1270-1275.
[67] BOUVIER F, RAHIER A, CAMARA B. Biogenesis, molecular regulation and function of plant isoprenoids[J]. Progress in Lipid Research, 2005, 44(6): 357-429.
[68] BRANDT W, BRÄUER L, GÜNNEWICH N, et al. Molecular and structural basis of metabolic diversity mediated by prenyldiphosphate converting enzymes[J]. Phytochemistry, 2009, 70(15): 1758-1775.
[69] WANG K C, OHNUMA S I. Isoprenyl diphosphate synthases[J]. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 2000, 1529(1): 33-48.
[70] WESSJOHANN L A, BRANDT W, THIEMANN T. Biosynthesis and metabolism of cyclopropane rings in natural compounds[J]. Chemical Reviews, 2003, 103(4): 1625-1648.
[71] BOTTA B, DELLE MONACHE G, MENENDEZ P, et al. Novel prenyltransferase enzymes as a tool for flavonoid prenylation[J]. Trends in Pharmacological Sciences, 2005, 26(12): 606-608.
[72] PALSULEDESAI C C, DISTEFANO M D. Protein prenylation: enzymes, therapeutics, and biotechnology applications[J]. ACS Chemical Biology, 2015, 10(1): 51-62.
[73] CHANG H Y, CHENG T H, WANG A H J. Structure, catalysis, and inhibition mechanism of prenyltransferase[J]. IUBMB Life, 2021, 73(1): 40-63.
[74] ZIRPEL B, STEHLE F, KAYSER O. Production of Δ9-tetrahydrocannabinolic acidfrom cannabigerolic acid by whole cells of Pichia (Komagataella) pastoris expressing Δ9-tetrahydrocannabinolic acid synthase from Cannabis sativa L.[J]. Biotechnology Letters, 2015, 37: 1869-1875.
[75] ZIRPEL B, DEGENHARDT F, MARTIN C, et al. Engineering yeasts as platform organisms for cannabinoid biosynthesis[J]. Journal of Biotechnology, 2017, 259: 204-212.
[76] LUO X, REITER M A, D’ESPAUX L, et al. Complete biosynthesis of cannabinoids and their unnatural analogues in yeast[J]. Nature, 2019, 567(7746): 123-126.
[77] TAN Z, CLOMBURG J M, GONZALEZ R. Synthetic pathway for the production of olivetolic acid in Escherichia coli[J]. ACS Synthetic Biology, 2018, 7(8): 1886-1896.
[78] QIAN S, CLOMBURG J M, GONZALEZ R. Engineering Escherichia coli as a platform for the in vivo synthesis of prenylated aromatics[J]. Biotechnology and Bioengineering, 2019, 116(5): 1116-1127.
[79] VALLIERE M A, KORMAN T P, WOODALL N B, et al. A cell-free platform for the prenylation of natural products and application to cannabinoid production[J]. Nature Communications, 2019, 10(1): 565-573.
[80] 彭思琪. 大麻二酚酸合成毕赤酵母菌株的构建及优化[D]. 广东: 华南理工大学发酵工程学科硕士学位论文, 2021: 15-88.
[81] CUI G, LI X, MERZ K M. Understanding the substrate selectivity and the product regioselectivity of Orf2-catalyzed aromatic prenylations[J]. Biochemistry, 2007, 46(5): 1303-1311.
[82] KUMANO T, RICHARD S B, NOEL J P, et al. Chemoenzymatic syntheses of prenylated aromatic small molecules using Streptomyces prenyltransferases with relaxed substrate specificities[J]. Bioorganic & Medicinal Chemistry, 2008, 16(17): 8117-8126.
[83] YANG Y, MIAO Y, WANG B, et al. Catalytic mechanism of aromatic prenylation by NphB[J]. Biochemistry, 2012, 51(12): 2606-2618.
[84] FISCHER E. Einfluss der configuration auf die wirkung der enzyme[J]. Berichte der Deutschen Chemischen Gesellschaft, 1894, 27(3): 2985-2993.
[85] KOSHLAND JR D E. The key–lock theory and the induced fit theory[J]. Angewandte Chemie International Edition in English, 1995, 33(23): 2375-2378.
[86] MA B, KUMAR S, TSAI C J, et al. Folding funnels and binding mechanisms[J]. Protein Engineering, 1999, 12(9): 713-720.
[87] GOODSELL D S, MORRIS G M, OLSON A J. Automated docking of flexible ligands: applications of AutoDock[J]. Journal of Molecular Recognition, 1996, 9(1): 1-5.
[88] OSHIRO C M, KUNTZ I D, DIXON J S. Flexible ligand docking using a genetic algorithm[J]. Journal of Computer-Aided Molecular Design, 1995, 9: 113-130.
[89] GOODSELL D S, OLSON A J. Automated docking of substrates to proteins by simulated annealing[J]. Proteins: Structure, Function, and Bioinformatics, 1990, 8(3): 195-202.
[90] HOU T, WANG J, CHEN L, et al. Automated docking of peptides and proteins by using a genetic algorithm combined with a tabu search[J]. Protein Engineering, 1999, 12(8): 639-648.
[91] VERLET L. Computer” experiments” on classical fluids. I. Thermodynamical properties of Lennard-Jones molecules[J]. Physical Review, 1967, 159(1): 98-103.
[92] BROOKS B R, BRUCCOLERI R E, OLAFSON B D, et al. CHARMM: a program formacromolecular energy, minimization, and dynamics calculations[J]. Journal of Computational Chemistry, 1983, 4(2): 187-217.
[93] CORNELL W D, CIEPLAK P, BAYLY C I, et al. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules[J]. Journal of the American Chemical Society, 1995, 117(19): 5179-5197.
[94] OTT K H, MEYER B. Parametrization of GROMOS force field for oligosaccharides and assessment of efficiency of molecular dynamics simulations[J]. Journal of Computational Chemistry, 1996, 17(8): 1068-1084.
[95] THOMPSON A P, AKTULGA H M, BERGER R, et al. LAMMPS-a flexible simulation tool for particle-based materials modeling at the atomic, meso, and continuum scales[J]. Computer Physics Communications, 2022, 271: 108171-108204.
[96] SMITH W, YONG C, RODGER P. DL_POLY: Application to molecular simulation[J]. Molecular Simulation, 2002, 28(5): 385-471.
[97] GALE J D, ROHL A L. The general utility lattice program (GULP)[J]. Molecular Simulation, 2003, 29(5): 291-341.
[98] VAN DER SPOEL D, LINDAHL E, HESS B, et al. GROMACS: fast, flexible, and free[J]. Journal of Computational Chemistry, 2005, 26(16): 1701-1718.
[99] CASE D A, CHEATHAM III T E, DARDEN T, et al. The Amber biomolecular simulation programs[J]. Journal of Computational Chemistry, 2005, 26(16): 1668-1688.
[100] PHILLIPS J C, BRAUN R, WANG W, et al. Scalable molecular dynamics with NAMD[J]. Journal of Computational Chemistry, 2005, 26(16): 1781-1802.
[101] BROOKS B R, BROOKS III C L, MACKERELL JR A D, et al. CHARMM: the biomolecular simulation program[J]. Journal of Computational Chemistry, 2009, 30(10): 1545-1614.
[102] KIRKWOOD J G. Statistical mechanics of fluid mixtures[J]. The Journal of Chemical Physics, 1935, 3(5): 300-313.
[103] KITA Y, ARAKAWA T, LIN T Y, et al. Contribution of the surface free energy perturbation to protein-solvent interactions[J]. Biochemistry, 1994, 33(50): 15178-15189.
[104] SOUAILLE M, ROUX B. Extension to the weighted histogram analysis method: combining umbrella sampling with free energy calculations[J]. Computer Physics Communications, 2001, 135(1): 40-57.
[105] KOLLMAN P A, MASSOVA I, REYES C, et al. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models[J]. Accounts of Chemical Research, 2000, 33(12): 889-897.
[106] DELANO W L, et al. Pymol: An open-source molecular graphics tool[J]. CCP4 Newsl. Protein Crystallogr, 2002, 40(1): 82-92.
[107] FRISCH M, TRUCKS G, SCHLEGEL H, et al. Gaussian 16, Revision A. 03, Gaussian[J]. Inc., Wallingford CT, 2016, 3.
[108] TROTT O, OLSON A J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading[J]. Journal of Computational Chemistry, 2010, 31(2): 455-461.
[109] JURRUS E, ENGEL D, STAR K, et al. Improvements to the APBS biomolecular solvation software suite[J]. Protein Science, 2018, 27(1): 112-128.
[110] ROE D R, CHEATHAM III T E. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data[J]. Journal of Chemical Theory and Computation, 2013, 9(7): 3084-3095.
[111] 夏文豪，陈贤情，李珍珠，逯晓云，王筱，刘诗梦，杨月，黄利辉，李子鹤，王千，江会锋，王文. 异戊烯基转移酶突变体及生产大麻萜酚的方法: 中国,CN114350635A[P]. 2022-04-15.
[112] LIM K J H, HARTONO Y D, XUE B, et al. Structure-guided engineering of prenyltransferase NphB for high-yield and regioselective cannabinoid production[J]. ACS Catalysis, 2022, 12(8): 4628-4639.