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MetaCyc Pathway: kauralexin biosynthesis
Inferred from experimentAuthor statement

Pathway diagram: kauralexin biosynthesis

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisSecondary Metabolites BiosynthesisPhytoalexins BiosynthesisTerpenoid Phytoalexins Biosynthesis
BiosynthesisSecondary Metabolites BiosynthesisTerpenoids BiosynthesisDiterpenoids Biosynthesis

Some taxa known to possess this pathway include : Zea mays

Expected Taxonomic Range: Embryophyta

General Background

Kauralexins are a class of ent-kaurene-related diterpenoid defense compounds found in maize. They are produced in response to a variety of biotic threats, including the larvae of the European corn borer Ostrinia nubilalis and fungi such as Rhizopus microsporus and Fusarium graminearum. Jasmonic acid and ethylene can also work synergistically to promote kauralexin production. Kauralexins can also be detected in the scutella of 19 diverse maize inbred lines suggesting that these compounds are broadly or universally expressed among all maize varieties [Schmelz11].

Importantly, at low concentrations, kauralexin A3 and kauralexin B3 reduce the growth of R. microsporus and C.graminicola. In addition, in choice and nonchoice assays Ostrinia nubilalis consume less tissue treated with these compounds than untreated control tissue, indicating that kauralexins also have anti-feedant properties [Schmelz11].

About This Pathway

Although many of the compounds in this pathway have been identified experimentally, notably kauralexin A1, A2, A3, and B1, B2, and B3 [Schmelz11] the overall pathway scheme is proposed largely based on the sequence of enzymatic activities observed in other terpenoid biosynthetic routes, such as juvenile hormone III biosynthesis I.

Several lines of evidence suggest that kauralexin production depends on the activity of An2, including the increased level of An2 transcripts that accumulate prior to kauralexin accumulation [Schmelz11].

Tranformation of ent-CPP to ent-kaurene and ent-isokaurene likely requires the activity two different synthases. In rice, these labdane-related diterpene cyclases show show quite stringent specificity. For example, OsKS1 (kaurane synthase 1) produces ent-kaurene whereas OsKSL5/6 (kaurane-synthase-like 5/6) appears to primarily catalyze the formation of ent-isokaurene [Xu07]. Maize may have similarly stereospecific kaurene synthases.

The remainder of the reactions in the pathway are likely catalyzed by one or more cytochrome p450 enzymes and the predicted NADPH cofactors and oxygen inputs have been included on that basis. It is likely that these p450 enzymes would catalyze the formation of an alcohol and then its conversion to an aldehyde and finally a carboxylic acid to give rise to kauralexin A1 and kauralexin B1. The same series of reactions would likely be repeated on a different carbon atom to produce first two alcohols (not shown) followed by aldehydes kauralexin A3 and kauralexin B3 and finally the dicarboxylates kauralexin A2 and kauralexin B2. This series of reactions has been observed for several other p450 enzymes that act in plant secondary metabolism, such as those that participate in costunolide biosynthesis and gibberellin metabolism [Prosser02, Nguyen10b, Helliwell01].

Identification of all of the unknown enzymes and the intermediate compounds that participate in kauralexin biosynthesis will lead to a better understanding of this overall pathway and its role in maize defense against fungi, herbivory, and other biotic threats.

Citations: [Mellon79]

Subpathways: ent-kaurene biosynthesis I

Created 09-Sep-2011 by Dreher KA, PMN


Helliwell01: Helliwell CA, Sullivan JA, Mould RM, Gray JC, Peacock WJ, Dennis ES (2001). "A plastid envelope location of Arabidopsis ent-kaurene oxidase links the plastid and endoplasmic reticulum steps of the gibberellin biosynthesis pathway." Plant J 28(2);201-8. PMID: 11722763

Mellon79: Mellon JE, West CA (1979). "Diterpene biosynthesis in maize seedlings in response to fungal infection." Plant Physiol 64(3);406-10. PMID: 16660976

Nguyen10b: Nguyen DT, Gopfert JC, Ikezawa N, Macnevin G, Kathiresan M, Conrad J, Spring O, Ro DK (2010). "Biochemical conservation and evolution of germacrene A oxidase in asteraceae." J Biol Chem 285(22);16588-98. PMID: 20351109

Prosser02: Prosser I, Phillips AL, Gittings S, Lewis MJ, Hooper AM, Pickett JA, Beale MH (2002). "(+)-(10R)-Germacrene A synthase from goldenrod, Solidago canadensis; cDNA isolation, bacterial expression and functional analysis." Phytochemistry 60(7);691-702. PMID: 12127586

Schmelz11: Schmelz EA, Kaplan F, Huffaker A, Dafoe NJ, Vaughan MM, Ni X, Rocca JR, Alborn HT, Teal PE (2011). "Identity, regulation, and activity of inducible diterpenoid phytoalexins in maize." Proc Natl Acad Sci U S A 108(13);5455-60. PMID: 21402917

Xu07: Xu M, Wilderman PR, Morrone D, Xu J, Roy A, Margis-Pinheiro M, Upadhyaya NM, Coates RM, Peters RJ (2007). "Functional characterization of the rice kaurene synthase-like gene family." Phytochemistry 68(3);312-26. PMID: 17141283

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

Cho04a: Cho EM, Okada A, Kenmoku H, Otomo K, Toyomasu T, Mitsuhashi W, Sassa T, Yajima A, Yabuta G, Mori K, Oikawa H, Toshima H, Shibuya N, Nojiri H, Omori T, Nishiyama M, Yamane H (2004). "Molecular cloning and characterization of a cDNA encoding ent-cassa-12,15-diene synthase, a putative diterpenoid phytoalexin biosynthetic enzyme, from suspension-cultured rice cells treated with a chitin elicitor." Plant J 37(1);1-8. PMID: 14675427

Doehlemann08: Doehlemann G, Wahl R, Horst RJ, Voll LM, Usadel B, Poree F, Stitt M, Pons-Kuhnemann J, Sonnewald U, Kahmann R, Kamper J (2008). "Reprogramming a maize plant: transcriptional and metabolic changes induced by the fungal biotroph Ustilago maydis." Plant J 56(2);181-95. PMID: 18564380

Harris05: Harris LJ, Saparno A, Johnston A, Prisic S, Xu M, Allard S, Kathiresan A, Ouellet T, Peters RJ (2005). "The maize An2 gene is induced by Fusarium attack and encodes an ent-copalyl diphosphate synthase." Plant Mol Biol 59(6);881-94. PMID: 16307364

Hayashi06: Hayashi K, Kawaide H, Notomi M, Sakigi Y, Matsuo A, Nozaki H (2006). "Identification and functional analysis of bifunctional ent-kaurene synthase from the moss Physcomitrella patens." FEBS Lett 580(26);6175-81. PMID: 17064690

Kanno06: Kanno Y, Otomo K, Kenmoku H, Mitsuhashi W, Yamane H, Oikawa H, Toshima H, Matsuoka M, Sassa T, Toyomasu T (2006). "Characterization of a rice gene family encoding type-A diterpene cyclases." Biosci Biotechnol Biochem 70(7);1702-10. PMID: 16861806

Kawaide00: Kawaide H, Sassa T, Kamiya Y (2000). "Functional analysis of the two interacting cyclase domains in ent-kaurene synthase from the fungus Phaeosphaeria sp. L487 and a comparison with cyclases from higher plants." J Biol Chem 275(4);2276-80. PMID: 10644675

Kawaide97: Kawaide H, Imai R, Sassa T, Kamiya Y (1997). "Ent-kaurene synthase from the fungus Phaeosphaeria sp. L487. cDNA isolation, characterization, and bacterial expression of a bifunctional diterpene cyclase in fungal gibberellin biosynthesis." J Biol Chem 272(35);21706-12. PMID: 9268298

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

Nemoto04: Nemoto T, Cho EM, Okada A, Okada K, Otomo K, Kanno Y, Toyomasu T, Mitsuhashi W, Sassa T, Minami E, Shibuya N, Nishiyama M, Nojiri H, Yamane H (2004). "Stemar-13-ene synthase, a diterpene cyclase involved in the biosynthesis of the phytoalexin oryzalexin S in rice." FEBS Lett 571(1-3);182-6. PMID: 15280039

Otomo04: Otomo K, Kenmoku H, Oikawa H, Konig WA, Toshima H, Mitsuhashi W, Yamane H, Sassa T, Toyomasu T (2004). "Biological functions of ent- and syn-copalyl diphosphate synthases in rice: key enzymes for the branch point of gibberellin and phytoalexin biosynthesis." Plant J 39(6);886-93. PMID: 15341631

Sponsel04: Sponsel V.M., Hedden P. (2004). "Gibberellin biosynthesis and inactivation." Plant Hormones. Biosynthesis, Signal transduction, Action! Kluwer Academic Publishers, Ed. P.J. Davies.

Sun94: Sun TP, Kamiya Y (1994). "The Arabidopsis GA1 locus encodes the cyclase ent-kaurene synthetase A of gibberellin biosynthesis." Plant Cell 1994;6(10);1509-18. PMID: 7994182

Toyomasu00: Toyomasu T, Kawaide H, Ishizaki A, Shinoda S, Otsuka M, Mitsuhashi W, Sassa T (2000). "Cloning of a full-length cDNA encoding ent-kaurene synthase from Gibberella fujikuroi: functional analysis of a bifunctional diterpene cyclase." Biosci Biotechnol Biochem 64(3);660-4. PMID: 10803977

Xu07a: Xu M, Wilderman PR, Peters RJ (2007). "Following evolution's lead to a single residue switch for diterpene synthase product outcome." Proc Natl Acad Sci U S A 104(18);7397-401. PMID: 17456599

Yamaguchi98: Yamaguchi S, Sun T, Kawaide H, Kamiya Y (1998). "The GA2 locus of Arabidopsis thaliana encodes ent-kaurene synthase of gibberellin biosynthesis." Plant Physiol 1998;116(4);1271-8. PMID: 9536043

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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