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|
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].
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
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.
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
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
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.
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
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