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discounted EARLY registration ends Dec 31, 2014
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MetaCyc Pathway: camptothecin biosynthesis

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Secondary Metabolites Biosynthesis Nitrogen-Containing Secondary Compounds Biosynthesis Alkaloids Biosynthesis Quinoline Alkaloids Biosynthesis

Some taxa known to possess this pathway include ? : Camptotheca , Camptotheca acuminata , Nothapodytes nimmoniana , Ophiorrhiza japonica , Ophiorrhiza pumila Traceable author statement to experimental support [Asano12]

Expected Taxonomic Range: Apocynaceae , Camptotheca , Icacinaceae , Nyssaceae , Rubiaceae

Summary:
Camptothecin (CPT) is a monoterpene indole alkaloid, that was isolated from the Chinese happy tree, Camptotheca acuminata. This compound has drawn considerable interest among drug researchers as it was shown to possess anti-tumor activity. The exact mechanism of anti-cancerous activity has been pinpointed to camptothecin being an inhibitor of topoisomerase 1. Camptothecin inhibits religation of DNA strands that are nicked, by reversibly binding to the cleavable complex. This prevents binding of DNA polymerase and creates a double strand break. Subsequent downstream events are fatal to the cell. Camptothecin is derived biosynthetically from L-tryptophan and secologanine, by the formation of the precursor strictosidine. For camptothecin biosynthesis the key precursor from strictosidine is the formation of strictosamide. It is not clear whether this reaction is catalyzed enzymatically or spontaneously [Sirikantaramas09].

The last three steps of the pathway also remain speculative, however, there is evidence for both intermediate compounds (pumiloside and deoxypumiloside) in Ophiorrhiza pumila. Moreover, in this species, genetic suppression of the upstream enzymes in this pathway leads to a decrease in the levels of these intermediates. Nevertheless, the complex steps involved and the enzymes required to convert strictosamide to camptothecin have not yet been identified [Asano12].

Credits:
Created 03-Sep-2009 by Pujar A , Boyce Thompson Institute
Revised 08-Jan-2013 by Dreher KA , PMN


References

Asano12: Asano T, Kobayashi K, Kashihara E, Sudo H, Sasaki R, Iijima Y, Aoki K, Shibata D, Saito K, Yamazaki M (2012). "Suppression of camptothecin biosynthetic genes results in metabolic modification of secondary products in hairy roots of Ophiorrhiza pumila." Phytochemistry. PMID: 22652243

Sirikantaramas09: Sirikantaramas S, Yamazaki M, Saito K (2009). "A survival strategy: The coevolution of the camptothecin biosynthetic pathway and self-resistance mechanism." Phytochemistry. PMID: 19709698

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Aimi89: Aimi N, Nishimura M, Miwa A, Hoshino H, Sakai SI, Haginiwa J (1989). "Pumiloside and deoxypumiloside; plausible intermediates of camptothecin biosynthesis." Tetrahedron Letters 30(37);4991-4994.

Bertoldi00: Bertoldi M, Borri Voltattorni C (2000). "Reaction of dopa decarboxylase with L-aromatic amino acids under aerobic and anaerobic conditions." Biochem J 352 Pt 2;533-8. PMID: 11085948

Buki85: Buki KG, Vinh DQ, Horvath I (1985). "Partial purification and some properties of tryptophan decarboxylase from a Bacillus strain." Acta Microbiol Hung 32(1);65-73. PMID: 4036551

Burkhard01: Burkhard P, Dominici P, Borri-Voltattorni C, Jansonius JN, Malashkevich VN (2001). "Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase." Nat Struct Biol 8(11);963-7. PMID: 11685243

Fernandez89: Fernandez, J.A., Owen, T.G., Kurz, W.G.W., De Luca, V.D. (1989). "Immunological detection and quantitation of tryptophan decarboxylase in developing Catharanthus roseus seedlings." Plant Physiol. 91: 79-84.

Ichinose85: Ichinose H, Kojima K, Togari A, Kato Y, Parvez S, Parvez H, Nagatsu T (1985). "Simple purification of aromatic L-amino acid decarboxylase from human pheochromocytoma using high-performance liquid chromatography." Anal Biochem 150(2);408-14. PMID: 4091266

Irmler00: Irmler S, Schroder G, St-Pierre B, Crouch NP, Hotze M, Schmidt J, Strack D, Matern U, Schroder J (2000). "Indole alkaloid biosynthesis in Catharanthus roseus: new enzyme activities and identification of cytochrome P450 CYP72A1 as secologanin synthase." Plant J 24(6);797-804. PMID: 11135113

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

LopezMeyer97: Lopez-Meyer M, Nessler CL (1997). "Tryptophan decarboxylase is encoded by two autonomously regulated genes in Camptotheca acuminata which are differentially expressed during development and stress." Plant J 11(6);1167-75. PMID: 9225462

Lu09: Lu Y, Wang H, Wang W, Qian Z, Li L, Wang J, Zhou G, Kai G (2009). "Molecular characterization and expression analysis of a new cDNA encoding strictosidine synthase from Ophiorrhiza japonica." Mol Biol Rep 36(7);1845-52. PMID: 18987991

Moore96: Moore PS, Dominici P, Borri Voltattorni C (1996). "Cloning and expression of pig kidney dopa decarboxylase: comparison of the naturally occurring and recombinant enzymes." Biochem J 315 ( Pt 1);249-56. PMID: 8670114

Nakazawa77: Nakazawa, H., Sano, K., Kumagai, H., Yamada, H. (1977). "Distribution and formation of aromatic L-amino acid decarboxylase in bacteria." Agric. Biol.. Chem. 41(11):2241-2247.

Noe84: Noe, W., Mollenschott, C., Berlin, J. (84). "Tryptophan decarboxylase from Catharanthus roseus cell suspension cultures: purification, molecular and kinetic data of the homogeneous protein." Plant Mol Biol 3: 281-288.

Treimer79: Treimer JF, Zenk MH (1979). "Purification and properties of strictosidine synthase, the key enzyme in indole alkaloid formation." Eur J Biochem 101(1);225-33. PMID: 510306

Yamazaki03: Yamazaki Y, Sudo H, Yamazaki M, Aimi N, Saito K (2003). "Camptothecin biosynthetic genes in hairy roots of Ophiorrhiza pumila: cloning, characterization and differential expression in tissues and by stress compounds." Plant Cell Physiol 44(4);395-403. PMID: 12721380

Yamazaki03a: Yamazaki Y, Urano A, Sudo H, Kitajima M, Takayama H, Yamazaki M, Aimi N, Saito K (2003). "Metabolite profiling of alkaloids and strictosidine synthase activity in camptothecin producing plants." Phytochemistry 62(3);461-70. PMID: 12620359

Zhang01b: Zhang Z, ElSohly HN, Jacob MR, Pasco DS, Walker LA, Clark AM (2001). "New indole alkaloids from the bark of Nauclea orientalis." J Nat Prod 64(8);1001-5. PMID: 11520214


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Dec 18, 2014, biocyc11.