MetaCyc Pathway: superpathway of benzoxazinoid glucosides biosynthesis
Inferred from experiment

Enzyme View:

Pathway diagram: superpathway of benzoxazinoid glucosides biosynthesis

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.

Synonyms: benzoxazinoids biosynthesis, DIBOA / DIMBOA biosynthesis

Superclasses: BiosynthesisSecondary Metabolites Biosynthesis

Some taxa known to possess this pathway include : Coix lacryma-jobi, Triticum aestivum, Zea mays

Expected Taxonomic Range: Magnoliophyta

General Background

Benzoxazinoids were identified in the early 1960s as secondary metabolites of the grasses (including the major agricultural crops maize ( Zea mays), wheat ( Triticum aestivum), and rye ( Secale cereale)) that function as natural pesticides and exhibit allelopathic properties [Barnes87, Sicker00]. Benzoxazinoids are synthesized in two subfamilies of the Poaceae and sporadically in single species of the dicots [Frey09]. They play an important role in defense against pests such as insects, pathogenic fungi and bacteria [Niemeyer88]. The most common benzoxazinoids are DIBOA and DIMBOA.

Since the aglycone benzoxazinoids (see superpathway of benzoxazinoid glucosides biosynthesis) are autotoxic, they are stored in glucosylated forms that have reduced chemical reactivity [Sicker00]. The glucosides are stored in the vacuoles [Osbourn96]. This allows the plants to store the toxic compounds in anticipation of pathogen attacks, prompting the suggestion to name these compounds "phytoanticipins".

About This Pathway

The synthesis of benzoxazinoids starts with the cleavage of indole-3-glycerol phosphate (an intermediate in tryptophan biosynthesis) to form indole. Indole is a volatile compound and can be used, in conjunction with several terpenoids, to form cocktails of volatile products that are used in parasitic defense [Gierl01]. However, indole can be directed to the pathway described here, where is it converted into benzoxazinoids by a series of cytochrome P450-dependent monooxygenases. In successive reactions catalyzed by Bx2, Bx3, Bx4 and Bx5 four oxygen atoms are introduced into the indole moiety, producing DIBOA, which is glucosylated by the enzymes Bx8 and Bx9, forming DIBOA-β-D-glucoside.

While DIBOA is the main benzoxazinoid in some plants, including barley, in other plants, such as maize, DIBOA-β-D-glucoside is further converted to DIMBOA-β-D-glucoside by a two-step hydroxylation/methylation at position C7, catalyzed by Bx6 and Bx7, respectively [Jonczyk08].

DIMBOA-β-D-glucoside has been reported to be further methylated into HMDBOA-glucoside [Oikawa02]. HMDBOA-glucoside is relatively lipophilic amongst benzoxazinoid glucosides, a property that may affect its absorption by pathogens at the site of interaction [Oikawa02]. Action of β-glucosidases on HMDBOA-glucoside releases HDMBOA, which is highly unstable and degrades quickly into MBOA, an important allelochemical [Friebe98, Oikawa04]. A number of defense reaction elicitors (chitin and chitosan fragments, heavy metal ions such as copper and jasmonic acid) have been shown to lead to the production of HDMBOA-glucoside in wheat, maize and Job's Tears plants [Oikawa01, Oikawa02].

The proteins catalyzing the many steps of this pathway have been found in maize to be encoded by a cluster of genes on chromosome 4 (Bx1 to Bx8). Most of those genes have been confirmed to be involved in this pathway by mutant analysis as well as heterologous expression of the genes in yeast [Frey97].

Subpathways: DIMBOA-glucoside biosynthesis, DIBOA-glucoside biosynthesis

Created 05-Aug-2005 by Tissier C, PMN
Revised 04-Apr-2011 by Pujar A, Boyce Thompson Institute
Revised 28-Oct-2011 by Caspi R, SRI International


Barnes87: Barnes J.P., Putnam A.R. "Role of benzoxazinones in allelopathy by rye (Secale cereale L.)." J. Chem. Ecol. (1987) 13 : 889-906.

Frey03: Frey M, Huber K, Park WJ, Sicker D, Lindberg P, Meeley RB, Simmons CR, Yalpani N, Gierl A (2003). "A 2-oxoglutarate-dependent dioxygenase is integrated in DIMBOA-biosynthesis." Phytochemistry 62(3);371-6. PMID: 12620350

Frey09: Frey M, Schullehner K, Dick R, Fiesselmann A, Gierl A (2009). "Benzoxazinoid biosynthesis, a model for evolution of secondary metabolic pathways in plants." Phytochemistry 70(15-16);1645-51. PMID: 19577780

Frey97: Frey M, Chomet P, Glawischnig E, Stettner C, Grun S, Winklmair A, Eisenreich W, Bacher A, Meeley RB, Briggs SP, Simcox K, Gierl A (1997). "Analysis of a chemical plant defense mechanism in grasses." Science 277(5326);696-9. PMID: 9235894

Friebe98: Friebe A, Vilich V, Hennig L, Kluge M, Sicker D (1998). "Detoxification of Benzoxazolinone Allelochemicals from Wheat by Gaeumannomyces graminis var. tritici, G. graminis var. graminis, G. graminis var. avenae, and Fusarium culmorum." Appl Environ Microbiol 64(7);2386-91. PMID: 9647804

Gierl01: Gierl A, Frey M (2001). "Evolution of benzoxazinone biosynthesis and indole production in maize." Planta 213(4);493-8. PMID: 11556781

Glawischnig99: Glawischnig E, Grun S, Frey M, Gierl A (1999). "Cytochrome P450 monooxygenases of DIBOA biosynthesis: specificity and conservation among grasses." Phytochemistry 50(6);925-30. PMID: 10385992

Jonczyk08: Jonczyk R, Schmidt H, Osterrieder A, Fiesselmann A, Schullehner K, Haslbeck M, Sicker D, Hofmann D, Yalpani N, Simmons C, Frey M, Gierl A (2008). "Elucidation of the final reactions of DIMBOA-glucoside biosynthesis in maize: characterization of Bx6 and Bx7." Plant Physiol 146(3);1053-63. PMID: 18192444

Niemeyer88: Niemeyer H.M. (1988). "Hydroxamic acids (4-hydroxy-1,4-benzoxazin-3-ones), defence chemicals in the gramineae." Phytochemistry 27(11) : 3349-3358.

Oikawa01: Oikawa A, Ishihara A, Hasegawa M, Kodama O, Iwamura H (2001). "Induced accumulation of 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside (HDMBOA-Glc) in maize leaves." Phytochemistry 56(7);669-75. PMID: 11314951

Oikawa02: Oikawa A, Ishihara A, Iwamura H (2002). "Induction of HDMBOA-Glc accumulation and DIMBOA-Glc 4-O-methyltransferase by jasmonic acid in poaceous plants." Phytochemistry 61(3);331-7. PMID: 12359519

Oikawa04: Oikawa A, Ishihara A, Tanaka C, Mori N, Tsuda M, Iwamura H (2004). "Accumulation of HDMBOA-Glc is induced by biotic stresses prior to the release of MBOA in maize leaves." Phytochemistry 65(22);2995-3001. PMID: 15504434

Osbourn96: Osbourn AE (1996). "Preformed Antimicrobial Compounds and Plant Defense against Fungal Attack." Plant Cell 8(10);1821-1831. PMID: 12239364

Sicker00: Sicker D, Frey M, Schulz M, Gierl A (2000). "Role of natural benzoxazinones in the survival strategy of plants." Int Rev Cytol 198;319-46. PMID: 10804466

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

Ahmad11: Ahmad S, Veyrat N, Gordon-Weeks R, Zhang Y, Martin J, Smart L, Glauser G, Erb M, Flors V, Frey M, Ton J (2011). "Benzoxazinoid metabolites regulate innate immunity against aphids and fungi in maize." Plant Physiol 157(1);317-27. PMID: 21730199

Crawford60: CRAWFORD IP (1960). "Identification of the triose phosphate formed in the tryptophan synthetase reaction." Biochim Biophys Acta 45;405-7. PMID: 13696310

Frey00: Frey M, Stettner C, Pare PW, Schmelz EA, Tumlinson JH, Gierl A (2000). "An herbivore elicitor activates the gene for indole emission in maize." Proc Natl Acad Sci U S A 97(26);14801-6. PMID: 11106389

Frey95: Frey M, Kliem R, Saedler H, Gierl A (1995). "Expression of a cytochrome P450 gene family in maize." Mol Gen Genet 246(1);100-9. PMID: 7823905

Glawischnig97: Glawischnig, E., Eisenreich W., Bacher A., Frey M., Gierl A. (1997). "Biosynthetic origin of oxygen atoms in DIMBOA from maize: NMR studies of 18O2." Phytochemistry 45(4):715-718.

Hettwer02: Hettwer S, Sterner R (2002). "A novel tryptophan synthase beta-subunit from the hyperthermophile Thermotoga maritima. Quaternary structure, steady-state kinetics, and putative physiological role." J Biol Chem 277(10);8194-201. PMID: 11756459

Kirschner75: Kirschner K, Wiskocil RL, Foehn M, Rezeau L (1975). "The tryptophan synthase from Escherichia coli. An improved purification procedure for the alpha-subunit and binding studies with substrate analogues." Eur J Biochem 60(2);513-23. PMID: 1107044

Kramer95: Kramer VC, Koziel MG (1995). "Structure of a maize tryptophan synthase alpha subunit gene with pith enhanced expression." Plant Mol Biol 27(6);1183-8. PMID: 7766899

Kuo12: Kuo HH, Mauk AG (2012). "Indole peroxygenase activity of indoleamine 2,3-dioxygenase." Proc Natl Acad Sci U S A 109(35);13966-71. PMID: 22891315

Lane91: Lane AN, Kirschner K (1991). "Mechanism of the physiological reaction catalyzed by tryptophan synthase from Escherichia coli." Biochemistry 30(2);479-84. PMID: 1899028

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

Lawrence04: Lawrence SD, Novak NG (2004). "Maize genes induced by herbivory and volicitin." J Chem Ecol 30(12);2543-57. PMID: 15724970

Lazarowski03: Lazarowski ER, Shea DA, Boucher RC, Harden TK (2003). "Release of cellular UDP-glucose as a potential extracellular signaling molecule." Mol Pharmacol 63(5);1190-7. PMID: 12695547

Tang00: Tang XF, Ezaki S, Atomi H, Imanaka T (2000). "Biochemical analysis of a thermostable tryptophan synthase from a hyperthermophilic archaeon." Eur J Biochem 267(21);6369-77. PMID: 11029579

vonRad01: von Rad U, Huttl R, Lottspeich F, Gierl A, Frey M (2001). "Two glucosyltransferases are involved in detoxification of benzoxazinoids in maize." Plant J 28(6);633-42. PMID: 11851909

Weischet76: Weischet WO, Kirschner K (1976). "The mechanism of the synthesis of indoleglycerol phosphate catalyzed by tryptophan synthase from Escherichia coli. Steady-state kinetic studies." Eur J Biochem 65(2);365-73. PMID: 949971

Weischet76a: Weischet WO, Kirschner K (1976). "Steady-state kinetic studies of the synthesis of indoleglycerol phosphate catalyzed by the alpha subunit of tryptophan synthase from Escherichia coli. Comparison with the alpha2 beta2-complex." Eur J Biochem 65(2);375-85. PMID: 949972

Yutani87: Yutani K, Ogasahara K, Tsujita T, Kanemoto K, Matsumoto M, Tanaka S, Miyashita T, Matsushiro A, Sugino Y, Miles EW (1987). "Tryptophan synthase alpha subunit glutamic acid 49 is essential for activity. Studies with 19 mutants at position 49." J Biol Chem 262(28);13429-33. PMID: 2888759

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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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