MetaCyc Pathway: betalamic acid biosynthesis
Traceable author statement to experimental supportInferred from experiment

Enzyme View:

Pathway diagram: betalamic acid 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.

Superclasses: BiosynthesisSecondary Metabolites BiosynthesisNitrogen-Containing Secondary Compounds BiosynthesisAlkaloids BiosynthesisBetalaine Alkaloids Biosynthesis

Some taxa known to possess this pathway include : Amanita muscaria, Beta vulgaris, Portulaca grandiflora

Expected Taxonomic Range: Caryophyllales, Fungi

General Background

Betalains are water-soluble, chromo-alkaloid pigments that replace the anthocyanins in most families of the Caryophyllales order [Cai05]. Except for the families Caryophyllaceae and Molluginacea the two subclasses of betalains, i.e. betacyanins and betaxanthins dominate that order and provide violet and yellow cues to flowers, fruits and vegetative tissues, respectively [Strack03] [Grotewold06]. Betaxanthins have also been shown to emit green fluorescence which creates contrasting flower color patterns and might serve as signal or guide for pollinators [GandiaHerrero05]. The mutual exclusion of betalains and anthocyanins makes this compound class a useful chemotaxonomic criterion to differentiate families within the Caryophyllales order [Wyler61]. It appears that both pigment pathways may originate from common ancestors as an anthocyanin like regulator, i.e. MYB1 was identified in Beta vulgaris being able to up- or downregulate betalain biosynthesis [Hatlestad15]. The MYB1 in Beta vulgaris has been discussed as being acquired at the time when both pigment pathways were splitting up and is regarded an exciting example for an transcription factor being co-opted out of an existing anthocyanin pathway to regulate the very different betalain pathway instead [Davies15, Gerritsen15].

Those pigments have also been identified in a restricted number of basidiomycetes such as in the genera Amanita and Hygrocybe. No betacyanin pigments have been found in those fungi but the biosynthesis of several betaxanthin compounds along with other derivatives of betalamic acid such as muscaflavin and muscapurpurin has been established [Mueller97a]. However, their physiological role in fungi remains completely unknown [Strack03].

The term 'betalain' had been coined by Wohlpart and Mabry [Wohlpart68] to point out the derivation of these pigments from betalamic acid. Although similar in function to the anthocyanins, betalains are structural diverse compounds biosynthesized in a different way.

Betalains are induced after pathogenic attacks and wounding [Steddom03] and are biosynthetically influenced by light through competing pathways [Endress84]. Betalains are compounds that have found use as colorants in the food industry, the horticultural sector or the agroscience industry [Kujala00] [Stintzing00]. Recently, they have been considered as potential antioxidants which effectuated intensified corresponding research addressing certain oxidative stress-related disorders in humans [Kanner01] [Butera02] [Tesoriere03].

About This Pathway

The central intermediate for both betacyanin ( betacyanin biosynthesis) and betaxanthin biosynthesis ( betaxanthin biosynthesis (via dopaxanthin), betaxanthin biosynthesis (via dopamine), betaxanthin biosynthesis) is betalamic acid which derives from 3,4-dihydroxy-L-phenylalanine (DOPA) [GandiaHerrero10]. The key-enzyme, i.e. the extradiol ring-opening DOPA-4,5-dioxygenase (DODA) catalyzes the formation of 4,5-seco-DOPA in plants which is, in a consecutive reaction, spontaneously converted to the chromophore betalamic acid [Christinet04]. The common or sugar beet Beta vulgaris is one of the oldest known and richest sources of betalain [Keller36] and was used to identify and biochemically characterize the 4,5-DOPA dioxygenase extradiol encoded by the gene DODA [GandiaHerrero12]. In fungi this enzyme also catalyzes the 2,3-extradiol cleavage of DOPA that produces muscaflavin, indicating a case of convergent evolution of this enzyme [Mueller97] [Mueller97a].

DOPA may be synthesized through two different pathways from L-tyrosine involving either a bifunctional tyrosinase [Steiner99] or a tyrosine hydroxylase that requires pteridin cofactors for its activity, the latter representing a new enzyme reported for this reaction [Yamamoto01a].

Superpathways: superpathway of betalain biosynthesis

Created 20-Nov-2006 by Foerster H, TAIR
Revised 11-Jun-2015 by Foerster H, Boyce Thompson Institute


Butera02: Butera D, Tesoriere L, Di Gaudio F, Bongiorno A, Allegra M, Pintaudi AM, Kohen R, Livrea MA (2002). "Antioxidant activities of sicilian prickly pear (Opuntia ficus indica) fruit extracts and reducing properties of its betalains: betanin and indicaxanthin." J Agric Food Chem 50(23);6895-901. PMID: 12405794

Cai05: Cai Y, Sun M, Corke H (2005). "HPLC characterization of betalains from plants in the amaranthaceae." J Chromatogr Sci 43(9);454-60. PMID: 16212790

Christinet04: Christinet L, Burdet FX, Zaiko M, Hinz U, Zryd JP (2004). "Characterization and functional identification of a novel plant 4,5-extradiol dioxygenase involved in betalain pigment biosynthesis in Portulaca grandiflora." Plant Physiol 134(1);265-74. PMID: 14730069

Davies15: Davies KM (2015). "Swapping one red pigment for another." Nat Genet 47(1);5-6. PMID: 25547597

Endress84: Endress R, Jager A, Kreis W (1984). "Catecholamine biosynthesis dependent on the dark in betacyaninforming Portulaca callus." Journal of Plant Physiology, 115, 291-295.

GandiaHerrero05: Gandia-Herrero F, Garcia-Carmona F, Escribano J (2005). "Botany: floral fluorescence effect." Nature 437(7057);334. PMID: 16163341

GandiaHerrero10: Gandia-Herrero F, Escribano J, Garcia-Carmona F (2010). "Structural implications on color, fluorescence, and antiradical activity in betalains." Planta 232(2);449-60. PMID: 20467875

GandiaHerrero12: Gandia-Herrero F, Garcia-Carmona F (2012). "Characterization of recombinant Beta vulgaris 4,5-DOPA-extradiol-dioxygenase active in the biosynthesis of betalains." Planta 236(1);91-100. PMID: 22270561

Gerritsen15: Gerritsen VB (2015). "Another shade of red." proteinspotlight 169 June issue.

Grotewold06: Grotewold E (2006). "The genetics and biochemistry of floral pigments." Annu Rev Plant Biol 57;761-80. PMID: 16669781

Hatlestad15: Hatlestad GJ, Akhavan NA, Sunnadeniya RM, Elam L, Cargile S, Hembd A, Gonzalez A, McGrath JM, Lloyd AM (2015). "The beet Y locus encodes an anthocyanin MYB-like protein that activates the betalain red pigment pathway." Nat Genet 47(1);92-6. PMID: 25436858

Kanner01: Kanner J, Harel S, Granit R (2001). "Betalains--a new class of dietary cationized antioxidants." J Agric Food Chem 49(11);5178-85. PMID: 11714300

Keller36: Keller W (1936). "Inheritance of some major color types in beets." Journal of Agricultural Research 52(1):27-38.

Kujala00: Kujala TS, Loponen JM, Klika KD, Pihlaja K (2000). "Phenolics and betacyanins in red beetroot (Beta vulgaris) root: distribution and effect of cold storage on the content of total phenolics and three individual compounds." J Agric Food Chem 48(11);5338-42. PMID: 11087483

Mueller97: Mueller LA, Hinz U, Uze M, Sautter C, Zryd J-P (1997). "Biochemical complementation of the betalain biosynthetic pathway in Portulaca grandiflora by a fungal 3,4-dihydroxyphenylalanine dioxygenase." Planta, 203, 260-263.

Mueller97a: Mueller LA, Hinz U, Zryd J-P (1997). "The formation of betalamic acid and muscaflavin by recombinant dopa-dioxygenase from Amanita." Phytochemistry, 44(4), 567-569.

Steddom03: Steddom K, Heidel G, Jones D, Rush CM (2003). "Remote Detection of Rhizomania in Sugar Beets." Phytopathology, 93(6), 720-726.

Steiner99: Steiner U, Schliemann W, Boehm H, Strack D (1999). "Tyrosinase involved in betalain biosynthesis of higher plants." Planta, 208, 114-124.

Stintzing00: Stintzing FC, Schieber A, Carle R (2000). "Rote Bete als faerbendes Lebensmittel - eine Bestandsaufnahme." Obst-, Gemuese- und Kartoffelverarbeitung, 85, 196-204.

Strack03: Strack D, Vogt T, Schliemann W (2003). "Recent advances in betalain research." Phytochemistry 62(3);247-69. PMID: 12620337

Tesoriere03: Tesoriere L, Butera D, D'Arpa D, Di Gaudio F, Allegra M, Gentile C, Livrea MA (2003). "Increased resistance to oxidation of betalain-enriched human low density lipoproteins." Free Radic Res 37(6);689-96. PMID: 12868496

Wohlpart68: Wohlpart A, Mabry TJ (1968). "On the Light Requirement for Betalain Biogenesis." Plant Physiol 43(3);457-459. PMID: 16656788

Wyler61: Wyler H, Dreiding AS (1961). "[On betacyanins, the nitrogen containing pigment of Centrospermae. Preliminary report.]." Experientia 17;23-5. PMID: 13831375

Yamamoto01a: Yamamoto K, Kobayashi M, Yoshitama K, Teramoto S, Kosamine A (2001). "Isolation and purification of tyrosine hydroxylase from Portulaca grandiflora." Plant Cell Physiol., 42(9), 969-975.

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

Arita02: Arita DY, Di Marco GS, Schor N, Casarini DE (2002). "Purification and characterization of the active form of tyrosine hydroxylase from mesangial cells in culture." J Cell Biochem 87(1);58-64. PMID: 12210722

Blau: Blau N, Bonafe L, Thony B "Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: diagnosis and genetics of dopa-responsive dystonia and sepiapterin reductase deficiency." Mol Genet Metab 74(1-2);172-85. PMID: 11592814

Cho98: Cho SH, Na JU, Youn H, Hwang CS, Lee CH, Kang SO (1998). "Tepidopterin, 1-O-(L-threo-biopterin-2'-yl)-beta-N-acetylglucosamine from Chlorobium tepidum." Biochim Biophys Acta 1379(1);53-60. PMID: 9468332

Cho99: Cho SH, Na JU, Youn H, Hwang CS, Lee CH, Kang SO (1999). "Sepiapterin reductase producing L-threo-dihydrobiopterin from Chlorobium tepidum." Biochem J 340 ( Pt 2);497-503. PMID: 10333495

Chung00: Chung HJ, Kim YA, Kim YJ, Choi YK, Hwang YK, Park YS (2000). "Purification and characterization of UDP-glucose:tetrahydrobiopterin glucosyltransferase from Synechococcus sp. PCC 7942." Biochim Biophys Acta 1524(2-3);183-8. PMID: 11113566

El83: El Mestikawy S, Glowinski J, Hamon M (1983). "Tyrosine hydroxylase activation in depolarized dopaminergic terminals--involvement of Ca2+-dependent phosphorylation." Nature 302(5911);830-2. PMID: 6133218

Haavik91: Haavik J, Le Bourdelles B, Martinez A, Flatmark T, Mallet J (1991). "Recombinant human tyrosine hydroxylase isozymes. Reconstitution with iron and inhibitory effect of other metal ions." Eur J Biochem 199(2);371-8. PMID: 1676967

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

Maier95: Maier J, Ninnemann H (1995). "Biosynthesis of pteridines in Neurospora crassa, Phycomyces blakesleeanus and Euglena gracilis: detection and characterization of biosynthetic enzymes." Photochem Photobiol 61(1);43-53. PMID: 7899493

Mataga91: Mataga N, Imamura K, Watanabe Y (1991). "6R-tetrahydrobiopterin perfusion enhances dopamine, serotonin, and glutamate outputs in dialysate from rat striatum and frontal cortex." Brain Res 551(1-2);64-71. PMID: 1680529

Oka82: Oka K, Ashiba G, Sugimoto T, Matsuura S, Nagatsu T (1982). "Kinetic properties of tyrosine hydroxylase purified from bovine adrenal medulla and bovine caudate nucleus." Biochim Biophys Acta 706(2);188-96. PMID: 6127111

Schallreuter94: Schallreuter KU, Wood JM, Pittelkow MR, Gutlich M, Lemke KR, Rodl W, Swanson NN, Hitzemann K, Ziegler I (1994). "Regulation of melanin biosynthesis in the human epidermis by tetrahydrobiopterin." Science 263(5152);1444-6. PMID: 8128228

Sjoerdsma65: Sjoerdsma A, Engelman K, Spector S, Udenfriend S (1965). "Inhibition of catecholamine synthesis in man with alpha-methyl-tyrosine, an inhibitor of tyrosine hydroxylase." Lancet 2(7422);1092-4. PMID: 4158803

Tanaka89: Tanaka K, Kaufman S, Milstien S (1989). "Tetrahydrobiopterin, the cofactor for aromatic amino acid hydroxylases, is synthesized by and regulates proliferation of erythroid cells." Proc Natl Acad Sci U S A 86(15);5864-7. PMID: 2762302

Thony00: Thony B, Auerbach G, Blau N (2000). "Tetrahydrobiopterin biosynthesis, regeneration and functions." Biochem J 347 Pt 1;1-16. PMID: 10727395

Wang11c: Wang H, Yang B, Hao G, Feng Y, Chen H, Feng L, Zhao J, Zhang H, Chen YQ, Wang L, Chen W (2011). "Biochemical characterization of the tetrahydrobiopterin synthesis pathway in the oleaginous fungus Mortierella alpina." Microbiology 157(Pt 11);3059-70. PMID: 21852350

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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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