Accelerating the semisynthesis of alkaloid-based drugs through metabolic engineering

Nature Chemical Biology

Volumn 13, Issue 3, 2017, Pages 249-258

  Ehrenworth, Amy M ^a   Peralta Yahya, Pamela ^a,b  

^a GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

^b Georgia Institute of Technology   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID; AMARYLLIDACEAE ALKALOID; APORPHINE DERIVATIVE; BENZYLISOQUINOLINE DERIVATIVE; ERGOT ALKALOID; INDOLE ALKALOID; ISOQUINOLINE DERIVATIVE; MORPHINAN DERIVATIVE; PHENYLALANINE DERIVATIVE; PYRROLOQUINOLINEQUINONE; QUINOLINE DERIVATIVE; TERPENE DERIVATIVE; TETRAHYDROISOQUINOLINE DERIVATIVE; TRYPTOPHAN; TYROSINE DERIVATIVE; DRUG;

BIOTECHNOLOGICAL PRODUCTION; DRUG SYNTHESIS; METABOLIC ENGINEERING; NONHUMAN; PRIORITY JOURNAL; REVIEW; BIOSYNTHESIS; CHEMISTRY; METABOLISM; PLANT;

ALKALOIDS; METABOLIC ENGINEERING; PHARMACEUTICAL PREPARATIONS; PLANTS;

EID: 85012896729     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.2308     Document Type: Review

References (100)

1. Newman, D.J. & Cragg, G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod. 79, 629-661 (2016
2. Chen, J., Li, W., Yao, H. & Xu, J. Insights into drug discovery from natural products through structural modification. Fitoterapia 103, 231-241 (2015
3. Rahier, N.J., Thomas, C.J. & Hecht, S.M. in Anticancer Agents from Natural Products. 2nd edn. (eds. Cragg, G., Kingston, D. & Newman, D.) 5-26 (CRC Press, 2011
4. Leonard, E., Runguphan, W., OConnor, S. & Prather, K.J. Opportunities in metabolic engineering to facilitate scalable alkaloid production. Nat. Chem. Biol. 5, 292-300 (2009
5. Dehghan, E., Hosseini, B., Naghdi Badi, H. & Shahriari Ahmadi, F. Application of conventional and new biotechnological approaches for improving of morphinane alkaloids production. J. Med. Plants 9, 33-50 (2010
6. Glenn, W.S., Runguphan, W. & OConnor, S.E. Recent progress in the metabolic engineering of alkaloids in plant systems. Curr. Opin. Biotechnol. 24, 354-365 (2013
7. Diamond, A. & Desgagne-Penix, I. Metabolic engineering for the production of plant isoquinoline alkaloids. Plant Biotechnol. J. 14, 1319-1328 (2016
8. Kulkarni, R.N., Baskaran, K. & Jhang, T. Breeding medicinal plant, periwinkle [Catharanthus roseus (L) G. Don]: a review. Plant Genet. Resour. 14, 283-302 (2016
9. Kosuri, S. & Church, G.M. Large-scale de novo DNA synthesis: technologies and applications. Nat. Methods 11, 499-507 (2014
10. Chao, R., Yuan, Y. & Zhao, H. Recent advances in DNA assembly technologies. FEMS Yeast Res. 15, 1-9 (2015
11. Narcross, L., Fossati, E., Bourgeois, L., Dueber, J.E. & Martin, V.J. Microbial factories for the production of benzylisoquinoline alkaloids. Trends Biotechnol. 34, 228-241 (2016
12. Ro, D.K. et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440, 940-943 (2006
13. Paddon, C.J. & Keasling, J.D. Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development. Nat. Rev. Microbiol. 12, 355-367 (2014
14. Peplow, M. Synthetic biology's first malaria drug meets market resistance. Nature 530, 389-390 (2016
15. Pickens, L.B., Tang, Y. & Chooi, Y.H. Metabolic engineering for the production of natural products. Annu. Rev. Chem. Biomol. Eng. 2, 211-236 (2011
16. OConnor, S.E. Strategies for engineering plant natural products: the iridoid-derived monoterpene indole alkaloids of Catharanthus roseus. Methods Enzymol. 515, 189-206 (2012
17. Runguphan, W., Qu, X. & OConnor, S.E. Integrating carbon-halogen bond formation into medicinal plant metabolism. Nature 468, 461-464 (2010
18. Glenn, W.S., Nims, E. & OConnor, S.E. Reengineering a tryptophan halogenase to preferentially chlorinate a direct alkaloid precursor. J. Am. Chem. Soc. 133, 19346-19349 (2011
19. Friedrich, A., Brase, S. & OConnor, S.E. Synthesis of 4-, 5-, 6-, and 7-azidotryptamines. Tetrahedr. Lett. 50, 75-76 (2009
20. Trenchard, I.J., Siddiqui, M.S., Thodey, K. & Smolke, C.D. De novo production of the key branch point benzylisoquinoline alkaloid reticuline in yeast. Metab. Eng. 31, 74-83 (2015
21. Brown, S., Clastre, M., Courdavault, V. & OConnor, S.E. De novo production of the plant-derived alkaloid strictosidine in yeast. Proc. Natl. Acad. Sci. USA 112, 3205-3210 (2015
22. Galanie, S. & Smolke, C.D. Optimization of yeast-based production of medicinal protoberberine alkaloids. Microb. Cell Fact. 14, 144 (2015
23. Li, Y. & Smolke, C.D. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast. Nat. Commun. 7, 12137 (2016
24. Trenchard, I.J. & Smolke, C.D. Engineering strategies for the fermentative production of plant alkaloids in yeast. Metab. Eng. 30, 96-104 (2015
25. Hori, K., Okano, S. & Sato, F. Efficient microbial production of stylopine using a Pichia pastoris expression system. Sci. Rep. 6, 22201 (2016
26. McKeague, M., Wang, Y.H., Cravens, A., Win, M.N. & Smolke, C.D. Engineering a microbial platform for de novo biosynthesis of diverse methylxanthines. Metab. Eng. 38, 191-203 (2016
27. Jakubczyk, D. et al. Discovery and reconstitution of the cycloclavine biosynthetic pathway-enzymatic formation of a cyclopropyl group. Angew. Chem. Weinheim Bergstr. Ger. 127, 5206-5210 (2015
28. Fossati, E., Narcross, L., Ekins, A., Falgueyret, J.P. & Martin, V.J. Synthesis of morphinan alkaloids in Saccharomyces cerevisiae. PLoS One 10, e0124459 (2015
29. Galanie, S., Thodey, K., Trenchard, I.J., Filsinger Interrante, M. & Smolke, C.D. Complete biosynthesis of opioids in yeast. Science 349, 1095-1100 (2015
30. Nakagawa, A. et al. Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli. Nat. Commun. 7, 10390 (2016
31. Qu, Y. et al. Completion of the seven-step pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeast. Proc. Natl. Acad. Sci. USA 112, 6224-6229 (2015
32. DeLoache, W.C. et al. An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose. Nat. Chem. Biol. 11, 465-471 (2015
33. Nielsen, C.A. et al. The important ergot alkaloid intermediate chanoclavine-I produced in the yeast Saccharomyces cerevisiae by the combined action of EasC and EasE from Aspergillus japonicus. Microb. Cell Fact. 13, 95 (2014
34. Thodey, K., Galanie, S. & Smolke, C.D. A microbial biomanufacturing platform for natural and semisynthetic opioids. Nat. Chem. Biol. 10, 837-844 (2014
35. Fossati, E. et al. Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae. Nat. Commun. 5, 3283 (2014
36. Nakagawa, A. et al. (R,S)-tetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli. Sci. Rep. 4, 6695 (2014
37. Ehrenworth, A.M., Sarria, S. & Peralta-Yahya, P. Pterin-dependent mono-oxidation for the microbial synthesis of a modified monoterpene indole alkaloid. ACS Synth. Biol. 4, 1295-1307 (2015
38. Wishart, D.S. et al. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 34, D668-D672 (2006
39. Hagel, J.M., Krizevski, R., Marsolais, F., Lewinsohn, E. & Facchini, P.J. Biosynthesis of amphetamine analogs in plants. Trends Plant Sci. 17, 404-412 (2012
40. Cuevas, C. et al. Synthesis of ecteinascidin ET-743 and phthalascidin Pt-650 from cyanosafracin B. Org. Lett. 2, 2545-2548 (2000
41. Meyer, T. et al. Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis treatment. PLoS Negl. Trop. Dis. 3, e357 (2009
42. Yu, Q.S. et al. Preparation and characterization of tetrabenazine enantiomers against vesicular monoamine transporter 2. ACS Med. Chem. Lett. 1, 105-109 (2010
43. Naito, R. et al. Synthesis and antimuscarinic properties of quinuclidin-3-yl 1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives as novel muscarinic receptor antagonists. J. Med. Chem. 48, 6597-6606 (2005
44. Ruff, B.M., Brase, S. & OConnor, S.E. Biocatalytic production of tetrahydroisoquinolines. Tetrahedr. Lett. 53, 1071-1074 (2012
45. Kilgore, M.B. & Kutchan, T.M. The Amaryllidaceae alkaloids: biosynthesis and methods for enzyme discovery. Phytochem. Rev. 15, 317-337 (2016
46. Marco-Contelles, J., do Carmo Carreiras, M., Rodriguez, C., Villarroya, M. & Garcia, A.G. Synthesis and pharmacology of galantamine. Chem. Rev. 106, 116-133 (2006
47. Chen, J.Q., Xie, J.H., Bao, D.H., Liu, S. & Zhou, Q.L. Total synthesis of (-)-galanthamine and (-)-lycoramine via catalytic asymmetric hydrogenation and intramolecular reductive Heck cyclization. Org. Lett. 14, 2714-2717 (2012
48. Kilgore, M.B., Augustin, M.M., May, G.D., Crow, J.A. & Kutchan, T.M. CYP96T1 of Narcissus sp. aff. pseudonarcissus catalyzes formation of the Para-Para'C-C phenol couple in the Amaryllidaceae alkaloids. Front. Plant Sci. 7, 225 (2016
49. Kilgore, M.B., Holland, C.K., Jez, J.M. & Kutchan, T.M. Identification of a noroxomaritidine reductase with Amaryllidaceae alkaloid biosynthesis related activities. J. Biol. Chem. 291, 16740-16752 (2016
50. Wang, R. et al. Chemical synthetic method for norbelladine. CN patent 103,408,439 (2013
51. Dewick, P.M. Medicinal Natural Products: A Biosynthetic Approach 3rd edn, 311-420 (Wiley, 2009
52. Nasreen, A., Rueffer, M. & Zenk, M.H. Cytochrome P-450-dependent formation of isoandrocymbine from autumnaline in colchicine biosynthesis. Tetrahedr. Lett. 37, 8161-8164 (1996
53. Hill, D.A. & Turner, G.L. Neuromuscular blocking agents. US Patent 5,453,510 (1995
54. Morishige, T., Tsujita, T., Yamada, Y. & Sato, F. Molecular characterization of the S-adenosyl-l-methionine:3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase involved in isoquinoline alkaloid biosynthesis in Coptis japonica. J. Biol. Chem. 275, 23398-23405 (2000
55. Ounaroon, A., Decker, G., Schmidt, J., Lottspeich, F. & Kutchan, T.M. (R,S)-Reticuline 7-O-methyltransferase and (R,S)-norcoclaurine 6-O-methyltransferase of Papaver somniferum-cDNA cloning and characterization of methyl transfer enzymes of alkaloid biosynthesis in opium poppy. Plant J. 36, 808-819 (2003
56. Chang, L., Hagel, J.M. & Facchini, P.J. Isolation and characterization of O-methyltransferases involved in the biosynthesis of glaucine in Glaucium flavum. Plant Physiol. 169, 1127-1140 (2015
57. Gurusamy, N. Process for making apomorphine and apocodeine. EP patent 2,007,730 (2008
58. Schaefer, B. in Natural Products in the Chemical Industry 260-296 (Springer-Verlag, 2014
59. Gesell, A. et al. CYP719B1 is salutaridine synthase, the C-C phenol-coupling enzyme of morphine biosynthesis in opium poppy. J. Biol. Chem. 284, 24432-24442 (2009
60. Park, S. et al. Production of serotonin by dual expression of tryptophan decarboxylase and tryptamine 5-hydroxylase in Escherichia coli. Appl. Microbiol. Biotechnol. 89, 1387-1394 (2011
61. Germann, S.M. et al. Glucose-based microbial production of the hormone melatonin in yeast Saccharomyces cerevisiae. Biotechnol. J. 11, 717-724 (2016
62. Baumann, M., Baxendale, I.R., Ley, S.V. & Nikbin, N. An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals. Beilstein J. Org. Chem. 7, 442-495 (2011
63. Dunn, P.J. Synthesis of commercial phosphodiesterase(V) inhibitors. Org. Process Res. Dev. 9, 88-97 (2005
64. OConnor, S.E. & Maresh, J.J. Chemistry and biology of monoterpene indole alkaloid biosynthesis. Nat. Prod. Rep. 23, 532-547 (2006
65. Hoareau, L. & DaSilva, E. Medicinal plants: a re-emerging health aid. Electron. J. Biotechnol. 2, http://dx.doi.org/10.2225/vol2-issue2-fulltext-2 (1999
66. Miettinen, K. et al. The seco-iridoid pathway from Catharanthus roseus. Nat. Commun. 5, 3606 (2014
67. Gngora-Castillo, E. et al. Development of transcriptomic resources for interrogating the biosynthesis of monoterpene indole alkaloids in medicinal plant species. PLoS One 7, e52506 (2012
68. Xiao, M. et al. Transcriptome analysis based on next-generation sequencing of non-model plants producing specialized metabolites of biotechnological interest. J. Biotechnol. 166, 122-134 (2013
69. Kellner, F. et al. Genome-guided investigation of plant natural product biosynthesis. Plant J. 82, 680-692 (2015
70. Hawkins, K.M. & Smolke, C.D. Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae. Nat. Chem. Biol. 4, 564-573 (2008
71. Kaufman, T.S. & Rveda, E.A. The quest for quinine: those who won the battles and those who won the war. Angew. Chem. Int. Edn Engl. 44, 854-885 (2005
72. Stork, G. et al. The first stereoselective total synthesis of quinine. J. Am. Chem. Soc. 123, 3239-3242 (2001
73. Isaac, J.E., Robins, R.J. & Rhodes, M.J.C. Cinchoninone:Nadph oxidoreductases i and ii-novel enzymes in the biosynthesis of quinoline alkaloids in Cinchona ledgeriana. Phytochemistry 26, 393-399 (1987
74. Comins, D.L. & Nolan, J.M. A practical six-step synthesis of (S)-camptothecin. Org. Lett. 3, 4255-4257 (2001
75. Rao, A.V.R., Rao, R., Yadav, J.S. & Khagga, M. Scalable synthetic route to 2-amino-5-hydroxypropiophenone: efficient formal synthesis of irinotecan. Synth. Commun. 43, 1661-1667 (2013
76. Zabudkin, A. Method for the synthesis of irinotecan. EP patent 2,881,396 (2015
77. Puri, S.C., Handa, G., Dhar, K.L., Suri, O.P. & Qazi, G.N. Process for preparing topotecan from 10-hydroxy-4-(S) camptothecin. EP patent 1,608,660 (2007
78. Lorence, A. & Nessler, C.L. Camptothecin, over four decades of surprising findings. Phytochemistry 65, 2735-2749 (2004
79. Pu, X. et al. Camptothecin-producing endophytic fungus Trichoderma atroviride LY357: isolation, identification, and fermentation conditions optimization for camptothecin production. Appl. Microbiol. Biotechnol. 97, 9365-9375 (2013
80. Cui, L. et al. Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila. Sci. Rep. 5, 8227 (2015
81. Ni, X.H. et al. Enhancement of camptothecin produciton in Camptotheca acuminara hairy roots by overexpressing ORCA3 gene. J. Appl. Pharm. Sci. 1, 85-88 (2011
82. Sadre, R. et al. Metabolite diversity in alkaloid biosynthesis: a multi-lane (diastereomer) highway for camptothecin synthesis in Camptotheca acuminata. Plant Cell 28, 1926-1944 (2016
83. McCoy, E. & OConnor, S.E. Directed biosynthesis of alkaloid analogs in the medicinal plant Catharanthus roseus. J. Am. Chem. Soc. 128, 14276-14277 (2006
84. Gerhards, N., Neubauer, L., Tudzynski, P. & Li, S.M. Biosynthetic pathways of ergot alkaloids. Toxins (Basel) 6, 3281-3295 (2014
85. Cvak, L. in Ergot: The Genus Claviceps (eds. Kren, V. & Cvak, L.) 373-408 (Harwood Academic Publishers, 1999
86. Ryan, K.L., Moore, C.T. & Panaccione, D.G. Partial reconstruction of the ergot alkaloid pathway by heterologous gene expression in Aspergillus nidulans. Toxins (Basel) 5, 445-455 (2013
87. Wallwey, C., Matuschek, M. & Li, S.M. Ergot alkaloid biosynthesis in Aspergillus fumigatus: conversion of chanoclavine-I to chanoclavine-I aldehyde catalyzed by a short-chain alcohol dehydrogenase FgaDH. Arch. Microbiol. 192, 127-134 (2010
88. Cheng, J.Z., Coyle, C.M., Panaccione, D.G. & OConnor, S.E. Controlling a structural branch point in ergot alkaloid biosynthesis. J. Am. Chem. Soc. 132, 12835-12837 (2010
89. Robinson, S.L. & Panaccione, D.G. Heterologous expression of lysergic acid and novel ergot alkaloids in Aspergillus fumigatus. Appl. Environ. Microbiol. 80, 6465-6472 (2014
90. McCoy, E., Galan, M.C. & OConnor, S.E. Substrate specificity of strictosidine synthase. Bioorg. Med. Chem. Lett. 16, 2475-2478 (2006
91. Lee, H.Y., Yerkes, N. & OConnor, S.E. Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis. Chem. Biol. 16, 1225-1229 (2009
92. Geu-Flores, F. et al. An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis. Nature 492, 138-142 (2012
93. Campbell, A. et al. Engineering of a nepetalactol-producing platform strain of Saccharomyces cerevisiae for the production of plant seco-iridoids. ACS Synth. Biol. 5, 405-414 (2016
94. Lang, A. et al. Changing the regioselectivity of the tryptophan 7-halogenase PrnA by site-directed mutagenesis. Angew. Chem. Int. Edn Engl. 50, 2951-2953 (2011
95. Brown, S. & OConnor, S.E. Halogenase engineering for the generation of new natural product analogues. ChemBioChem 16, 2129-2135 (2015
96. Runguphan, W. & OConnor, S.E. Diversification of monoterpene indole alkaloid analogs through cross-coupling. Org. Lett. 15, 2850-2853 (2013
97. Gillis, E.P., Eastman, K.J., Hill, M.D., Donnelly, D.J. & Meanwell, N.A. Applications of fluorine in medicinal chemistry. J. Med. Chem. 58, 8315-8359 (2015
98. OHagan, D. & Deng, H. Enzymatic fluorination and biotechnological developments of the fluorinase. Chem. Rev. 115, 634-649 (2015
99. Hong, H., Spiteller, D. & Spencer, J.B. Incorporation of fluoroacetate into an aromatic polyketide and its influence on the mode of cyclization. Angew. Chem. Int. Edn Engl. 47, 6028-6032 (2008
100. Walker, M.C. et al. Expanding the fluorine chemistry of living systems using engineered polyketide synthase pathways. Science 341, 1089-1094 (2013