Copalyl diphosphate

RAVN, M. M., COATES, R. M., FLORY, J. E., PETERS, R. J., CROTEAU, R., Stereochemistry of the cyclization-rearrangement of (+)-copalyl diphosphate to (-)-abietadiene catalyzed by recombinant abietadiene synthase from Abies grandis, Org. Lett., 2000, 2,573-576. 

Figure 5.7 Proposed mechanism for the cyclization of geranylgeranyl diphosphate (GGPP) to the diterpene copalyl diphosphate, an example of terpene synthase-catalysed cyclization initiated by double-bond protonation, rather than by hydrolysis of the diphosphate ester. PP indicates a diphosphate moiety.

Two major steps exist in the biosynthesis of diterpene resin acids the formation of the diterpene and the stepwise oxidation of the diterpene to the corresponding acid. Most conifer diterpenes are tricyclic they are biosynthesized by bifunctional di-TPS that first cyclize geranylgeranyl diphosphate to (+)-copalyl diphosphate and then cyclize this intermediate even... 

The mevalonate labelling pattern of the antibiotic pleuromutilin (5.130), which is produced by the Basidiomycete Pleurotus mutilus (Clitopilus scyphoides), suggests that it is formed (Scheme 5.12) by a more deep-seated rearrangement of a copalyl diphosphate (5.131 5.132 5.133). A derivative, tiamulin , is used in animal health and retapamulin (altabax ) has attracted interest because of its activity against resistant organisms where it selectively targets the bacterial ribosome. 

Pisum Is copalyl diphosphate metabolism in vitro, gene 55,97... 

Zea mays an 1 copalyl diphosphate synthase (CPS) gene isolation 56... 

Arabidopsis gal copalyl diphosphate synthase (CPS)Isolation of gene 53,54,107... 

The gibberellin family of compounds, derived from the olefin (-)-kaurene, have been identified in some fungi, and all plants where they function as phytohormones. In plants, (-)-kaurene is formed by two diterpene cyclases working in sequence, copalyl diphosphate synthase (enf-kaurene synthase A or (-)-CPP synthase) and enf-kaurene synthase (enf-kaurene synthase B or (-)-KS). (-)-CPP synthase catalyzes the protonation-initiated cyclization of GGPP to (-)-CPP, while (-)-KS cyclizes (-)-CPP into (-)-kaurene via an ionization-initiated mechanism (see Scheme 18). 

Monofunctional type II diterpene synthases from plants such as the cnf-copalyl diphosphate synthase from A. thaliana exhibit an apy-modular structure [201]. In this type of enzymes, the p-domain contains the conserved DXDD motif, but no DDXXD motif is present within the a-domain which coincides with the lack of... 

GGPP to copalyl diphosphate (CPP), followed by its transformation into abietadiene via 49 in a class I reaction (Scheme 87.20). Notably, the bifunctional plant terpene synthases are generally involved in the biosynthesis of a large superfamily of terpenes, the labdane-related diterpenoids [214]. 

Xu M, Hillwig ML, Prisic S, Coates RM, Peters RJ (2004) Functional identification of rice syn-copalyl diphosphate synthase and its role in initiating biosynthesis of diterpenoid phytoalexin/allelopathic natural products. Plant J 39 309... 

The diterpene synthase copalyl diphosphate synthase (CDP) is one of the most studied type B synthases. It forms the bicycUc intermediate (-)-copalyl pyrophosphate ((-)-CPP) or its diastereomer (+)-copalyl pyrophosphate ((+)-CPP) from GGPP. Several CDPs are expressed in rice OsCycl forms (+)-CPP, while OsCyc2 and OsCPSl form (-)-CPPs. OsCPSl is believed to be involved in gibberellin biosynthesis and OsCyc2 in diterpene phytoalexin biosynthesis [31],... 

Ikeda, C. et al. (2007) Functional analysis of eubacterial enf-copalyl diphosphate synthase andpimara-9(l 1),15-diene sjmthase with unique primary sequences. J. Biochem. 141, 37 5... 

Otomo, K. et al. (2004) Biological functions of ent- and syn-copalyl diphosphate synthases in rice key enzymes for the branch point of gib-berellin and phytoalexin biosjmthesis. Plant J. 

Peters, R.J., Ravn, M.M., Coates, R.M. and Croteau, R.B. (2001) Bifunctional abietadiene synthase Free diffusive transfer ofthe (+)-copalyl diphosphate intermediate between two distinct active sites. /. Am. Chem. Soc., 123, 8974-8978. 

Prisic, S., Xu, M.M., WUderman, P.R. and Peters, R.J. (2004) Rice contains two disparate ent-copalyl diphosphate synthases with distinct metabolic functions. Plant Physiol, 136, 4228 236. 

A series of ionization and proton-induced cycUzations 16 20 catalyzed by the taxadiene synthase convert GGPP 1 into the taxadienes 21 and 22 for en mute synthesis of biological important natural products such as taxol and analogs (Scheme 8.2) [7]. Abietanes andkauranes are important classes of diterpenes. In the presence of abietadiene synthase, 1 undergoes a proton-induced cascade cyclization to produce the copalyl diphosphate intermediate 23 (Scheme 8.2) [8]. The latter is converted to 24 via an ionic cyclization and then to 25 through a methyl 1,2-shift between C13 and C14 [9]. In contrast, diterpene mt-kaur-16-ene 29 is not formed via the same cyclase enzyme. Consequently, it was proposed that two enzymes, mt-copalyl diphosphate and cnt-kaurene... 

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