Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
twitter

MetaCyc Pathway: superpathway of rosmarinic acid biosynthesis

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

Superclasses: Biosynthesis Secondary Metabolites Biosynthesis Phenylpropanoid Derivatives Biosynthesis Cinnamates Biosynthesis
Superpathways

Some taxa known to possess this pathway include ? : Anchusa officinalis , Lithospermum erythrorhizon , Portulaca grandiflora , Solenostemon scutellarioides

Expected Taxonomic Range: Tracheophyta

Summary:
General Background

This superpathway illustrates the metabolic steps of the rosmarinic acid biosynthesis. Rosmarinic acid (RA) is an ester of caffeic acid and 3,4-dihydrophenyllactic acid and is widely spread in species of the Lamiaceae and Boraginaceae [Petersen03a] but also occurs in lower plants such as ferns and hornworts [Takeda90a] [Petersen03]. Beside rosmarinic acid its 3'-O-β-glucoside (rosmarinic acid 3'-O-β-glucoside) has been identified in the hornwort Anthoceros agrestis [Vogelsang05] accumulating up to 1% of the cell dry weight. Other rosmarinic acid derivatives of biological importance are lithospermic acid, a conjugate of rosmarinic acid and caffeic acid, and lithospermic acid B a dimer of rosmarinic acid [Petersen03a].

The biosynthesis of rosmarinic acid has been extensively studied for two reasons. Rosmarinic acid has been shown to be a useful compound with regard to medicine virtue and as food additive. In addition, RA is considered as a preformed, constitutively accumulated compound involved in the defense against microbes [Szabo99]. The other reason was the challenge to unravel the interesting biosynthesis consisting of two parallel biosynthetic pathways that have to be regulated in a coordinated manner [Matsuno02].

About This Pathway

RA biosynthesis has been first investigated in Mentha arvense and Mentha x piperita [Ellis70] confirming the involvement of two parallel pathways for the making of rosmarinic acid. The metabolic origin for the formation of the two crucial compounds coumaroyl-CoA and 4-hydroxyphenyllactate was identified as L-phenylalanine and L-tyrosine, respectively. The most experimental support for the RA biosynthesis has been obtained from species of the Lamiaceae family (Solenostemon scutellarioides,Anchusa officinalis) elucidating the detailed enzymatic steps resulting in the formation of RA (rosmarinic acid biosynthesis I) [Petersen93] [Petersen03a].

Coumaroyl-CoA is one of the essential components being used for the assembly of rosmarinic acid. It is derived from L-phenylalanine in three well characterized enzymatic steps in plants catalyzed by L-phenylalanine-ammonia-lyase (PAL), cinnamic acid 4-hydroxylase (C4H) and 4-coumaric acid-CoA ligase (4CL) (compare phenylpropanoid biosynthesis, initial reactions).

The other metabolic branch contributing to the biosynthesis of RA originates from L-tyrosine resulting in the formation of 4-hydroxyphenyllactate (4HPL). The two moieties of the parallel pathways are connected by rosmarinic acid synthase (RAS) catalyzing a transesterification reaction [Petersen88] [Petersen91]. The RAS accepted caffeoyl-CoA and 3,4-dihydroxyphenyllactic acid (DHPL) resulting in the formation of rosmarinic acid. It should be noted that only the R(+)-stereoisomer of 3,4-dihydroxyphenyllactic acid is accepted by the RAS. On the other side 4-coumaroyl-CoA and either DHPL or its monohydroxylated isomer, 4-hydroxyphenyllactic acid (pHPL) was converted to their corresponding coumaroyl-hydroxyphenyllactates.

The enzymatic capability of RAS and the precedent enzyme hydroxypuruvate reductase [Hausler91] [Kim04g] to accept different substrates (mono- or dihydroxylated forms of phenyllactates/phenylacetates) prompted the proposition for a potential second biosynthetic route for RA (rosmarinic acid biosynthesis II). The enzyme catalyzing the entry step into this potential pathway is tyrosine hydroxylase (EC 1.14.16.2) and has been purified from Portulaca grandiflora [Yamamoto01a]. The formation of L-3,4-dihydroxyphenylalanine (DOPA) can also be accomplished by the action of polyphenol oxidases (EC 1.10.3.1) (e.g. [Dry94]).

It is not known precisely at what stage or order in the rosmarinic acid biosynthesis the two hydroxygroups in the 3- and 3'-position of the phenolic rings of 4-coumaroyl-4'-hydroxyphenyllactate are introduced. These two last steps are catalyzed by two separate cytochrome P450 dependent monooxygenases introducing hydroxyl groups to the 3- and 3'-position of 4-coumaroyl-4'-hydroxyphenyllactate [Petersen97] [Matsuno02]. Whereas the 3-hydroxylation of this hydroxycinnamic acid ester has been established the 3'-hydroxylation has yet to be fully characterized.

Subpathways: rosmarinic acid biosynthesis II , rosmarinic acid biosynthesis I

Credits:
Created 07-Sep-2006 by Foerster H , TAIR


References

Dry94: Dry IB, Robinson SP (1994). "Molecular cloning and characterisation of grape berry polyphenol oxidase." Plant Mol Biol 26(1);495-502. PMID: 7948897

Ellis70: Ellis BE, Towers GH (1970). "Biogenesis of rosmarinic acid in Mentha." Biochem J 118(2);291-7. PMID: 5484678

Hausler91: Hausler E, Petersen M, Alfermann AW (1991). "Hydroxyphenylpyruvate reductase from cell suspension cultures of Coleus blumei Benth." Z. Naturforsch. 46c, 371-376.

Kim04g: Kim KH, Janiak V, Petersen M (2004). "Purification, cloning and functional expression of hydroxyphenylpyruvate reductase involved in rosmarinic acid biosynthesis in cell cultures of Coleus blumei." Plant Mol Biol 54(3);311-23. PMID: 15284489

Matsuno02: Matsuno M, Nagatsu A, Ogihara Y, Ellis BE, Mizukami H (2002). "CYP98A6 from Lithospermum erythrorhizon encodes 4-coumaroyl-4'-hydroxyphenyllactic acid 3-hydroxylase involved in rosmarinic acid biosynthesis." FEBS Lett 514(2-3);219-24. PMID: 11943155

Petersen03: Petersen M (2003). "Cinnamic acid 4-hydroxylase from cell cultures of the hornwort Anthoceros agrestis.." Planta 217(1);96-101. PMID: 12721853

Petersen03a: Petersen M, Simmonds MS (2003). "Rosmarinic acid." Phytochemistry 62(2);121-5. PMID: 12482446

Petersen88: Petersen M, Alfermann AW (1988). "Two new enzymes of rosmarinic acid biosynthesis from cell cultures of Coleus blumei: Hydroxyphenylpyruvate reductase and rosmarinic acid synthase." Z. Naturforsch., 43c, 501-504.

Petersen91: Petersen M (1991). "Characterization of rosmarinic acid synthase from cell cultures of Coleus blumei." Phytochemistry, 30(9), 2877-2881.

Petersen93: Petersen M, Hausler E, Karwatzki B, Meinhard J (1993). "Proposed biosynthetic pathway for rosmarinic acid in cell cultures of Coleus blumei Benth." Planta, 189, 10-14.

Petersen97: Petersen M (1997). "Cytochrome p450-dependent hydroxylation in the biosynthesis of rosmarinic acid in Coleus." Phytochemistry, 45(6), 1165-1172.

Szabo99: Szabo E, Thelen A, Petersen M (1999). "Fungal elicitor preparations and methyl jasmonate enhance rosmarinic acid accumulation in in vitro-cultures of Coleus blumei." Plant Cell Rep. 18, 485-489.

Takeda90a: Takeda R, Hasegawa J, Shinozaki M (1990). "The first isolation of lignans, megacerotonic acid and anthocerotonic acid, from non-vascular plants, anthocerotae (hornworts)." Tetrahedron letters, 31(29), 4159-4162.

Vogelsang05: Vogelsang K, Schneider B, Petersen M (2005). "Production of rosmarinic acid and a new rosmarinic acid 3'-O-β-D: -glucoside in suspension cultures of the hornwort Anthoceros agrestis Paton." Planta NIL;1-5. PMID: 16133208

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

Andersson82: Andersson SM, Pispa JP (1982). "Purification and properties of human liver tyrosine aminotransferase." Clin Chim Acta 125(2);117-23. PMID: 6128088

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

Blakley77: Blakley ER (1977). "The catabolism of L-tyrosine by an Arthrobacter sp." Can J Microbiol 23(9);1128-39. PMID: 20216

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

Cho99a: 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

Collier72: Collier RH, Kohlhaw G (1972). "Nonidentity of the aspartate and the aromatic aminotransferase components of transaminase A in Escherichia coli." J Bacteriol 1972;112(1);365-71. PMID: 4404056

DeEknamkul87: De-Eknamkul W, Ellis BE (1987). "Purification and characterization of tyrosine aminotransferase activities from Anchusa officinalis cell cultures." Arch Biochem Biophys 257(2);430-8. PMID: 2889425

DeEknamkul87a: De-Eknamkul W, Ellis BE (1987). "Tyrosine aminotransferase: the entrypoint enzyme of the tyrosine-derived pathway in rosmarinic acid biosynthesis." Phytochemistry, 26(7), 1941-1946.

Dietrich91: Dietrich JB, Lorber B, Kern D (1991). "Expression of mammalian tyrosine aminotransferase in Saccharomyces cerevisiae and Escherichia coli. Purification to homogeneity and characterization of the enzyme overproduced in the bacteria." Eur J Biochem 201(2);399-407. PMID: 1682148

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

Gelfand77: Gelfand DH, Steinberg RA (1977). "Escherichia coli mutants deficient in the aspartate and aromatic amino acid aminotransferases." J Bacteriol 1977;130(1);429-40. PMID: 15983

Gu98: Gu W, Song J, Bonner CA, Xie G, Jensen RA (1998). "PhhC is an essential aminotransferase for aromatic amino acid catabolism in Pseudomonas aeruginosa." Microbiology 144 ( Pt 11);3127-34. PMID: 9846749

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

Mavrides75: Mavrides C, Orr W (1975). "Multispecific aspartate and aromatic amino acid aminotransferases in Escherichia coli." J Biol Chem 250(11);4128-33. PMID: 236311

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

Showing only 20 references. To show more, press the button "Show all references".


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sun Dec 21, 2014, biocyc14.