Carminic acid

Last updated
Carminic acid [1]
Carminic acid structure.svg
Carminic-acid-3D-balls.png
Names
IUPAC name
7-(β-D-Glucopyranosyl)-3,5,6,8-tetrahydroxy-1-methyl-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid
Systematic IUPAC name
3,5,6,8-Tetrahydroxy-1-methyl-9,10-dioxo-7-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-9,10-dihydroanthracene-2-carboxylic acid
Other names
Carminic acid
C.I. Natural Red 4
C.I. 75470
CI 75470
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.013.658 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 215-023-3
E number E120 (colours)
KEGG
PubChem CID
UNII
  • InChI=1S/C22H20O13/c1-4-8-5(2-6(24)9(4)22(33)34)13(25)10-11(15(8)27)16(28)12(18(30)17(10)29)21-20(32)19(31)14(26)7(3-23)35-21/h2,7,14,19-21,23-24,26,28-32H,3H2,1H3,(H,33,34)/t7-,14-,19+,20-,21-/m1/s1 Yes check.svgY
    Key: DGQLVPJVXFOQEV-NGOCYOHBSA-N Yes check.svgY
  • InChI=1/C22H20O13/c1-4-8-5(2-6(24)9(4)22(33)34)13(25)10-11(15(8)27)16(28)12(18(30)17(10)29)21-20(32)19(31)14(26)7(3-23)35-21/h2,7,14,19-21,23-24,26,28-32H,3H2,1H3,(H,33,34)/t7-,14-,19+,20-,21-/m1/s1
    Key: DGQLVPJVXFOQEV-NGOCYOHBBS
  • O=C(O)c2c(c3C(=O)c1c(O)c(c(O)c(O)c1C(=O)c3cc2O)[C@H]4O[C@@H]([C@@H](O)[C@H](O)[C@H]4O)CO)C
Properties
C22H20O13
Molar mass 492.38 g/mol
Melting point 120 °C (248 °F; 393 K) (decomposes)
Acidity (pKa)3.39, 5.78, 8.35, 10.27, 11.51 [2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Carminic acid (C22H20O13) is a red glucosidal hydroxyanthrapurin that occurs naturally in some scale insects, such as the cochineal, Armenian cochineal, and Polish cochineal. The insects produce the acid as a deterrent to predators. [3] An aluminum salt of carminic acid is the coloring agent in carmine, a pigment. [4] Natives of Peru had been producing cochineal dyes for textiles since at least 700 CE. [4] Synonyms are C.I. 75470 and C.I. Natural Red 4. [5]

Contents

The chemical structure of carminic acid consists of a core anthraquinone structure linked to a glucose sugar unit. Carminic acid was first synthesized in the laboratory by organic chemists in 1991. [6] [7] In 2018, researchers genetically engineered the microbe Aspergillus nidulans to produce carminic acid. [8]

It was previously thought that it contains α-D-glucopyranosyl residue, which was later redetermined to be the β-D-glucopyranosyl anomer. [9]

Female Dactylopius coccus on prickly pear cactus photographed by Frank Vincentz. Dactylopius coccus (Barlovento) 04 ies.jpg
Female Dactylopius coccus on prickly pear cactus photographed by Frank Vincentz.

Harvesting from cochineals

Carminic acid is commonly harvested from an American species scaled insects called Dactylopius coccus (or cochineals). [10] [11] Cochineals are parasitic scaled insects which are abundantly found on their host plants, the prickly pear cactus native to Mexico and South America. [12] The insects are either cultivated or harvested from wild populations, mainly for the wingless females of the species which attach themselves to the cactus and outnumber the winged males of the species two hundred to one. [13] Classically, cultivated species were grown from eggs placed by workers onto the cactus leaves and left to grow. There the female cochineals would remain immobile for about 3 months until being brushed off, collected, and dried for shipping. [13] Females possess concentrations of about 1.5% bodyweight of carminic acid and newborns about 3.0%. [10] The carminic acid is then extracted by soaking the dried cochineals in water, and additives are then added to alter dye colour and enable the dye to adhere to objects. [12]

Carminic acid released as the red substance seen on the person's hand after crushing Dactylopius coccus - by Dick Culbert. Dactylopius coccus (8410000864).jpg
Carminic acid released as the red substance seen on the person's hand after crushing Dactylopius coccus - by Dick Culbert.

Use as a deterrent

For many scaled insects of the genus Dactylopius, carminic acid, thoroughly documented by Thomas Eisner, has been shown to be a highly potent feeding deterrent against ants. [14] [15] In Eisner's 1980 paper, he notes that the red colour of the carminic acid released when the cochineals are crushed could also be a visual aposematic deterrent for predators as well. [15] However, he notes that tests have not been done on vertebrates to provide any support to that theory. [15] In the same paper however, Eisner mentions that cochineals were bitter when tasted by humans. [15]

Female (left) and male (right) cochineals Cochineal drawing.jpg
Female (left) and male (right) cochineals

Like other compounds housed in various plants, predators which are able to overcome the deterrent are able to sequester carminic acid in their flesh and utilize the deterrent for their own defense. [16] The pyralid moth ( Laetilia coccidivora ) is one such predator which feeds on cochineals, sequestering their prey's carminic acid in their own body for defense against predators. [14] [15] [16] The ability to sequester carminic acid has also been seen in several other larval bearing species (Hyperaspis, Leucopis, etc.). Eisner remarks that the ability to sequester the compound likely arose due to ants being a common predator amongst larvae [14] [16]

Biosynthesis of carminic acid

Biosynthesis of carminic acid Biosynthesis of carminic acid.jpg
Biosynthesis of carminic acid

Carminic acid is a polyketide secondary metabolite produced by the scale insect Dacylopius coccus . In terms of its biosynthetic origin, the structure of carminic acid was speculated to be either from type ll polyketide or shikimate pathways. This claim was not disputed until a key intermediate exclusive to the polyketide pathway was isolated. Until then, a detailed biosynthetic mechanism had not been formally proposed. [17]

The biosynthesis of carminic acid can be divided into three stages. The initiation stage involves transferases that load acetyl (AT) and malonyl-CoA (MCAT) to the acyl carrier protein (ACP) forming acetyl and malonyl-ACP, respectively. The acetyl-ACP acts as a priming unit for the decarboxylative condensation with malonyl-CoA catalyzed by a ketoacyl synthase (KS) protein. The resulting acetoacetyl ACP is the simplest polyketide produced by this pathway, and it is subsequently condensed with six more malonyl-ACP units before cyclizing. [17]

The elongation stage consists of the repeated decarboxylative condensation by a ketoacyl synthase/chain length factor heterodimer that monitors the length of the growing polyketide. The resulting octaketide is then aromatized by a cyclase domain which catalyzes an aldol-like cyclization reaction resulting in the formation of a flavokermesic acid anthrone (FKA). In any polyketide-based pathway, flavokermesic acid anthrone is the first cyclic intermediate. It was the successful isolation and characterization of FKA in wild type coccids that strengthened the evidence of a polyketide mediated biosynthetic pathway. [17]

The reactions that follow the formation of FKA consist of the aromatization and functionalization stages. FKA is subjected to two rounds of hydroxylation catalyzed by two distinct P450 monooxygenases forming flavokermesic acid and kermesic acid, respectively. Whether these monooxygenases are oxygen or flavin dependent is to be determined. The first monooxygenation occurs in the central aromatic ring carbon, C10 while the second occurs in the C4 position. The final attachment of a carbohydrate onto the C2 position C-glycosylation reaction is catalyzed by a UDP-glucose dependent membrane bound glucosyltransferase. The order of the last two steps has not been determined due to lack of experimental kinetic data. [17] [18]

Related Research Articles

Carmine – also called cochineal, cochineal extract, crimson lake, or carmine lake – is a pigment of a bright-red color obtained from the aluminium complex derived from carminic acid. Specific code names for the pigment include natural red 4, C.I. 75470, or E120. Carmine is also a general term for a particularly deep-red color.

A lake pigment is a pigment made by precipitating a dye with an inert binder, or mordant, usually a metallic salt. Unlike vermilion, ultramarine, and other pigments made from ground minerals, lake pigments are organic. Manufacturers and suppliers to artists and industry frequently omit the lake designation in the name. Many lake pigments are fugitive because the dyes involved are not lightfast. Red lakes were particularly important in Renaissance and Baroque paintings; they were often used as translucent glazes to portray the colors of rich fabrics and draperies.

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<span class="mw-page-title-main">Malonyl-CoA</span> Chemical compound

Malonyl-CoA is a coenzyme A derivative of malonic acid.

Polyketide synthases (PKSs) are a family of multi-domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages. The biosyntheses of polyketides share striking similarities with fatty acid biosynthesis.

<span class="mw-page-title-main">Chalcone synthase</span>

Chalcone synthase or naringenin-chalcone synthase (CHS) is an enzyme ubiquitous to higher plants and belongs to a family of polyketide synthase enzymes (PKS) known as type III PKS. Type III PKSs are associated with the production of chalcones, a class of organic compounds found mainly in plants as natural defense mechanisms and as synthetic intermediates. CHS was the first type III PKS to be discovered. It is the first committed enzyme in flavonoid biosynthesis. The enzyme catalyzes the conversion of 4-coumaroyl-CoA and malonyl-CoA to naringenin chalcone.

<span class="mw-page-title-main">Beta-ketoacyl-ACP synthase</span> Enzyme

In molecular biology, Beta-ketoacyl-ACP synthase EC 2.3.1.41, is an enzyme involved in fatty acid synthesis. It typically uses malonyl-CoA as a carbon source to elongate ACP-bound acyl species, resulting in the formation of ACP-bound β-ketoacyl species such as acetoacetyl-ACP.

<i>Kerria lacca</i> Species of true bug

Kerria lacca is a species of insect in the family Kerriidae, the lac insects. These are in the superfamily Coccoidea, the scale insects. This species is perhaps the most commercially important lac insect, being a main source of lac, a resin which can be refined into shellac and other products. This insect is native to Asia.

Zwittermicin A is an antibiotic that has been identified from the bacterium Bacillus cereus UW85. It is a molecule of interest to agricultural industry because it has the potential to suppress plant disease due to its broad spectrum activity against certain gram positive and gram negative prokaryotic micro-organisms. The molecule is also of interest from a metabolic perspective because it represents a new structural class of antibiotic and suggests a crossover between polyketide and non-ribosomal peptide biosynthetic pathways. Zwittermicin A is linear aminopolyol.

<span class="mw-page-title-main">Cochineal</span> Species of insect producing the crimson dye carmine

The cochineal is a scale insect in the suborder Sternorrhyncha, from which the natural dye carmine is derived. A primarily sessile parasite native to tropical and subtropical South America through North America, this insect lives on cacti in the genus Opuntia, feeding on plant moisture and nutrients. The insects are found on the pads of prickly pear cacti, collected by brushing them off the plants, and dried.

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<span class="mw-page-title-main">Apratoxin A</span> Chemical compound

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<span class="mw-page-title-main">Germicidin</span> Chemical compound

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<span class="mw-page-title-main">Ketoacyl synthase</span> Catalyst for a key step in fatty acid synthesis

Ketoacyl synthases (KSs) catalyze the condensation reaction of acyl-CoA or acyl-acyl ACP with malonyl-CoA to form 3-ketoacyl-CoA or with malonyl-ACP to form 3-ketoacyl-ACP. This reaction is a key step in the fatty acid synthesis cycle, as the resulting acyl chain is two carbon atoms longer than before. KSs exist as individual enzymes, as they do in type II fatty acid synthesis and type II polyketide synthesis, or as domains in large multidomain enzymes, such as type I fatty acid synthases (FASs) and polyketide synthases (PKSs). KSs are divided into five families: KS1, KS2, KS3, KS4, and KS5.

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<span class="mw-page-title-main">Pladienolide B</span> Chemical compound

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References

  1. ↑ "Carminic Acid" . The Merck Index . Royal Society of Chemistry. 2013.
  2. ↑ Atabey, Hasan; Sari, Hayati; Al-Obaidi, Faisal N. (28 April 2012). "Protonation Equilibria of Carminic Acid and Stability Constants of Its Complexes with Some Divalent Metal Ions in Aqueous Solution". Journal of Solution Chemistry. 41 (5): 793–803. doi:10.1007/s10953-012-9830-7. S2CID   95406643.
  3. ↑ Eisner, T.; Nowicki, S.; Goetz, M.; Meinwald, J. (1980). "Red Cochineal Dye (Carminic Acid): Its Role in Nature" . Science. 208 (4447): 1039–1042. Bibcode:1980Sci...208.1039E. doi:10.1126/science.208.4447.1039. ISSN   0036-8075. PMID   17779027. S2CID   40209712.
  4. 1 2 Jan Wouters, Noemi Rosario-Chirinos (1992). "Dye Analysis of Pre-Columbian Peruvian Textiles with High-Performance Liquid Chromatography and Diode-Array Detection". Journal of the American Institute for Conservation. The American Institute for Conservation of Historic &. 31 (2): 237–255. doi:10.2307/3179495. JSTOR   3179495.
  5. ↑ "Approved additives and E numbers". Food Standards Agency. Retrieved 2021-03-12.
  6. ↑ Allevi, P.; et al. (1991). "The First Total Synthesis of Carminic Acid". Journal of the Chemical Society, Chemical Communications. 18 (18): 1319–1320. doi:10.1039/C39910001319.
  7. ↑ Ishida, T.; Inoue, M.; Baba, K.; Kozawa, M.; Inoue, K.; Inouye, H. (1987). "Absolute configuration and structure of carminic acid existing as the potassium salt in Dactylopius cacti L". Acta Crystallographica Section C Crystal Structure Communications. 43 (8): 1541–1544. doi:10.1107/S0108270187091169.
  8. ↑ Miller, Brittney J. (25 March 2022). "Cochineal, a red dye from bugs, moves to the lab". Knowable Magazine. doi: 10.1146/knowable-032522-1 . Retrieved 28 March 2022.
  9. ↑ Fiecchi, Alberto; Galli, Mario Anastasia Giovanni; Gariboldi, Pierluigi (1981-03-01). "Assignment of the β configuration to the C-glycosyl bond in carminic acid". The Journal of Organic Chemistry. 46 (7): 1511. doi:10.1021/jo00320a061. ISSN   0022-3263.
  10. 1 2 Eisner, T.; Ziegler, R.; McCormick, J. L.; Eisner, M.; Hoebeke, E. R.; Meinwald, J. (1994). "Defensive use of an acquired substance (carminic acid) by predaceous insect larvae" . Experientia. 50 (6): 610–615. doi:10.1007/bf01921733. ISSN   0014-4754. PMID   8020623. S2CID   20179601.
  11. ↑ Eisner, T.; Nowicki, S.; Goetz, M.; Meinwald, J. (1980). "Red Cochineal Dye (Carminic Acid): Its Role in Nature" . Science. 208 (4447): 1039–1042. Bibcode:1980Sci...208.1039E. doi:10.1126/science.208.4447.1039. ISSN   0036-8075. PMID   17779027. S2CID   40209712.
  12. 1 2 Elena., Phipps (2010). Cochineal red : the art history of a color. Yale University Press. ISBN   978-0-300-15513-6. OCLC   559857310.
  13. 1 2 Lee, Raymond L. (1948). "Cochineal Production and Trade in New Spain to 1600" . The Americas. 4 (4): 449–473. doi:10.2307/977830. ISSN   0003-1615. JSTOR   977830. S2CID   143447468.
  14. 1 2 3 Eisner, T.; Ziegler, R.; McCormick, J. L.; Eisner, M.; Hoebeke, E. R.; Meinwald, J. (1994). "Defensive use of an acquired substance (carminic acid) by predaceous insect larvae" . Experientia. 50 (6): 610–615. doi:10.1007/bf01921733. ISSN   0014-4754. PMID   8020623. S2CID   20179601.
  15. 1 2 3 4 5 Eisner, T.; Nowicki, S.; Goetz, M.; Meinwald, J. (1980). "Red Cochineal Dye (Carminic Acid): Its Role in Nature" . Science. 208 (4447): 1039–1042. Bibcode:1980Sci...208.1039E. doi:10.1126/science.208.4447.1039. ISSN   0036-8075. PMID   17779027. S2CID   40209712.
  16. 1 2 3 Hoffmann, Klaus H. (2015). Insect molecular biology and ecology. ISBN   978-1-4822-3188-5. OCLC   877367447.
  17. 1 2 3 4 Rasmussen, Silas A.; Kongstad, Kenneth T.; Khorsand-Jamal, Paiman; Kannangara, Rubini Maya; Nafisi, Majse; Van Dam, Alex; Bennedsen, Mads; Madsen, Bjørn; Okkels, Finn; Gotfredsen, Charlotte H.; Staerk, Dan; Thrane, Ulf; Mortensen, Uffe H.; Larsen, Thomas O.; Frandsen, Rasmus J.N. (2018-05-01). "On the biosynthetic origin of carminic acid" (PDF). Insect Biochemistry and Molecular Biology. 96: 51–61. doi: 10.1016/j.ibmb.2018.03.002 . ISSN   0965-1748. PMID   29551461.
  18. ↑ Kannangara, Rubini; Siukstaite, Lina; Borch-Jensen, Jonas; Madsen, Bjørn; Kongstad, Kenneth T.; Staerk, Dan; Bennedsen, Mads; Okkels, Finn T.; Rasmussen, Silas A.; Larsen, Thomas O.; Frandsen, Rasmus J.N.; Møller, Birger L. (2017-12-07). "Characterization of a membrane-bound C-glucosyltransferase responsible for carminic acid biosynthesis in Dactylopius coccus Costa". Nature Communications. 8 (1): 1987. doi: 10.1038/s41467-017-02031-z . PMC   5719414 . PMID   29215010.
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