Neopinone isomerase is involved in codeine and morphine biosynthesis in opium poppy

Nature Chemical Biology

Volumn 15, Issue 4, 2019, Pages 384-390

  Dastmalchi, Mehran ^a,b   Chen, Xue ^a,b   Hagel, Jillian M ^a,b   Chang, Limei ^a,b   Chen, Rongji ^a,b   Ramasamy, Sukanya ^a   Yeaman, Sam ^a   Facchini, Peter J ^a,b  

^a UNIVERSITY OF CALGARY   (Canada)

^b Epimeron Inc   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CODEINE; ISOMERASE; MORPHINE; NEOMORPHINE; NEOPINE; NEOPINONE ISOMERASE; OPIATE; THEBAINE; UNCLASSIFIED DRUG; HYDROCODONE;

ARTICLE; BIOSYNTHESIS; CATALYSIS; CHEMICAL STRUCTURE; FUNGAL STRAIN; IN VITRO STUDY; ISOMER; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; ANALOGS AND DERIVATIVES; ENZYMOLOGY; METABOLISM; PAPAVER; PHYSIOLOGY;

CODEINE; HYDROCODONE; ISOMERASES; MORPHINE; OPIUM; PAPAVER; THEBAINE;

EID: 85063330392     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/s41589-019-0247-0     Document Type: Article

References (39)

1. Hagel, J. M. & Facchini, P. J. Benzylisoquinoline alkaloid metabolism: a century of discovery and a brave new world. Plant Cell Physiol. 54, 647–672 (2013).
2. Rinner, U. & Hudlicky, T. Synthesis of morphine alkaloids and derivatives. Top. Curr. Chem. 309, 33–66 (2012).
3. Seth, P., Rudd, R. A., Noonan, R. K. & Haegerich, T. M. Quantifying the epidemic of prescription opioid overdose deaths. Am. J. Public Health 108, 500–502 (2018).
4. Clark, A. K., Wilder, C. M. & Winstanley, E. L. A systematic review of community opioid overdose prevention and naloxone distribution programs. J. Addict. Med. 8, 153–163 (2014).
5. Galanie, S., Thodey, K., Trenchard, I. J., Filsinger Interrante, M. & Smolke, C. D. Complete biosynthesis of opioids in yeast. Science 349, 1095–1100 (2015).
6. Fossati, E., Narcross, L., Ekins, A., Falgueyret, J. P. & Martin, V. J. J. Synthesis of morphinan alkaloids in Saccharomyces cerevisiae. PLoS One 10, e0124459 (2015).
7. Horn, J. S., Paul, A. G. & Rapoport, H. Biosynthetic conversion of thebaine to codeinone. Mechanism of ketone formation from enol ether in vivo. J. Am. Chem. Soc. 100, 1895–1898 (1978).
8. Hagel, J. M. & Facchini, P. J. Dioxygenases catalyze the O-demethylation steps of morphine biosynthesis in opium poppy. Nat. Chem. Biol. 6, 273–275 (2010).
9. Gollwitzer, J., Lenz, R., Hampp, N. & Zenk, M. H. The transformation of neopinone to codeinone in morphine biosynthesis proceeds non-enzymatically. Tetrahedr. Lett. 34, 5703–5706 (1993).
10. Lenz, R. & Zenk, M. H. Stereoselective reduction of codeinone, the penultimate enzymic step during morphine biosynthesis in Papaver somniferum. Tetrahedr. Lett. 36, 2449–2452 (1995).
11. Unterlinner, B., Lenz, R. & Kutchan, T. M. Molecular cloning and functional expression of codeinone reductase: the penultimate enzyme in morphine biosynthesis in the opium poppy Papaver somniferum. Plant J. 18, 465–475 (1999).
12. Dastmalchi, M., Chang, L., Torres, M. A., Ng, K. K. S. & Facchini, P. J. Codeinone reductase isoforms with differential stability, efficiency and product selectivity in opium poppy. Plant J. 10.1111/tpj.13975 (2018).
13. Thodey, K., Galanie, S. & Smolke, C. D. A microbial biomanufacturing platform for natural and semisynthetic opioids. Nat. Chem. Biol. 10, 837–844 (2014).
14. Chen, X. et al. A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis. Nat. Chem. Biol. 14, 738–743 (2018).
15. Bruce, N. C., Wilmot, C. J., Jordan, K. N., Stephens, L. D. & Lowe, C. R. Microbial degradation of the morphine alkaloids. Purification and characterization of morphine dehydrogenase from Pseudomonas putida M10. Biochem. J. 274, 875–880 (1991).
16. French, C. E. & Bruce, N. C. Purification and characterization of morphinone reductase from Pseudomonas putida M10. Biochem. J. 301, 97–103 (1994).
17. French, C. E. et al. Biological production of semisynthetic opiates using genetically engineered bacteria. Biotechnology 13, 674–676 (1995).
18. Parker, H. I., Blaschke, G. & Rapoport, H. Biosynthetic conversion of thebaine to codeine. J. Am. Chem. Soc. 94, 1276–1282 (1972).
19. Nielsen, B., Röe, J. & Brochmann-Hanssen, E. Oripavine - a new opium alkaloid. Planta Med. 48, 205–206 (1983).
20. Ilari, A. et al. Structural basis of enzymatic (S)-norcoclaurine biosynthesis. J. Biol. Chem. 284, 897–904 (2009).
21. Chwastyk, M., Jaskolski, M. & Cieplak, M. Structure-based analysis of thermodynamic and mechanical properties of cavity-containing proteins–case study of plant pathogenesis-related proteins of class 10. FEBS J. 281, 416–429 (2014).
22. Kofler, S. et al. Stabilization of the dimeric birch pollen allergen Bet v 1 impacts its immunological properties. J. Biol. Chem. 289, 540–551 (2014).
23. Yan, Q., Qi, X., Jiang, Z., Yang, S. & Han, L. Characterization of a pathogenesis-related class 10 protein (PR-10) from Astragalus mongholicus with ribonuclease activity. Plant Physiol. Biochem. 46, 93–99 (2008).
24. Pollack, R. M. Enzymatic mechanisms for catalysis of enolization: ketosteroid isomerase. Bioorg. Chem. 32, 341–353 (2004).
25. Gates, M. The conversion of codeinone to codeine. J. Am. Chem. Soc. 75, 4340–4341 (1953).
26. Onoyovwe, A. et al. Morphine biosynthesis in opium poppy involves two cell types: sieve elements and laticifers. Plant Cell 25, 4110–4122 (2013).
27. Millgate, A. G. et al. Analgesia: morphine-pathway block in top1 poppies. Nature 431, 413–414 (2004).
28. Casañal, A. et al. The strawberry pathogenesis-related 10 (PR-10) Fra a proteins control flavonoid biosynthesis by binding to metabolic intermediates. J. Biol. Chem. 288, 35322–35332 (2013).
29. Clifton, B. E. et al. Evolution of cyclohexadienyl dehydratase from an ancestral solute-binding protein. Nat. Chem. Biol. 14, 542–547 (2018).
30. Kaltenbach, M. et al. Evolution of chalcone isomerase from a noncatalytic ancestor. Nat. Chem. Biol. 14, 548–555 (2018).
31. Desgagné-Penix, I. & Facchini, P. J. Systematic silencing of benzylisoquinoline alkaloid biosynthetic genes reveals the major route to papaverine in opium poppy. Plant J. 72, 331–344 (2012).
32. Zimin, A. V. et al. The MaSuRCA genome assembler. Bioinformatics 29, 2669–2677 (2013).
33. Stanke, M., Steinkamp, R., Waack, S. & Morgenstern, B. AUGUSTUS: a web server for gene finding in eukaryotes. Nucleic Acids Res. 32, W309–W312 (2004).
34. Hagel, J. M. et al. Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants. BMC Plant Biol. 15, 227 (2015).
35. Grabherr, M. G. et al. Full-length transcriptome assembly from RNA-seq data without a reference genome. Nat. Biotechnol. 29, 644–652 (2011).
36. Guindon, S. et al. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst. Biol. 59, 307–321 (2010).
37. Ronquist, F. et al. MrBayes 3.2: efficient Bayesian phylogenetic inference and model choice across a large model space. Syst. Biol. 61, 539–542 (2012).
38. Letunic, I. & Bork, P. Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation. Bioinformatics 23, 127–128 (2007).
39. Farrow, S. C., Hagel, J. M., Beaudoin, G. A. W., Burns, D. C. & Facchini, P. J. Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy. Nat. Chem. Biol. 11, 728–732 (2015).