MetaCyc Pathway: phylloquinol biosynthesis
Inferred from experiment

Enzyme View:

Pathway diagram: phylloquinol 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: vitamin K1 biosynthesis, phylloquinone biosynthesis

Superclasses: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisQuinol and Quinone BiosynthesisPhylloquinol Biosynthesis
BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisVitamins Biosynthesis

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Catharanthus roseus, Galium mollugo, Synechococcus elongatus, Synechococcus sp. PCC 7002, Synechocystis sp. PCC 6803

Expected Taxonomic Range: Cyanobacteria, Viridiplantae

General Background

The naphtoquinones phylloquinone and phylloquinol are both designated as vitamin K1. The former acts as electron transfer cofactor (known as A1) of photosystem I (PS I) in higher plants and cyanobacteria. It is very similar to a menaquinone (vitamin K2), a naphthoquinone which is common in non-photosynthetic microbes, in which it serves in anaerobic electron transport systems [Sharma96]. The only difference between phyloquinone and menaquinone is in the polyprenyl tail. Menaquinones contain 1-14 isoprene units, while phyloquinone contains a phytyl side chain of 4 units [Shimada05a].

Phylloquinone was given the name vitamin K by Dam in 1935 [Dam35] and was first isolated in 1939 from alfalfa [Almquist75].

It has been found that phylloquinone is not absolutely required for efficient electron transfer in PS I [Johnson00]. In Synechocystis sp. PCC 6803 benzoquinones such as plastoquinone-9, which usually act as secondary electron acceptors in PS II [Johnson01b, Sakuragi05], can efficiently replace phylloquinone in the A1-site of PS I as a one-electron cofactor. However, as shown in an Arabidopsis mutant the deficiency of phylloquinone causes distortions in the thylakoid structure of chloroplasts, may abolish PS I, and affects the functionality of PS II [Shimada05a].

The biosynthesis of phylloquinone was studied in detail in the cyanobacterium Synechocystis sp. PCC 6803 and the genes encoding enzymes of this pathway were identified by comparison with genes encoding enzymes of the menaquinone biosynthetic pathway in Escherichia coli (see superpathway of menaquinol-8 biosynthesis I) [Sharma96]. With the isolation and functional confirmation of the homolog genes in Synechocystis encoding for phytyl transferase, 1,4-dihydroxy-2-naphthoate synthase [Johnson00], 2-phytyl-1,4-naphthoquinone methyltransferase [Sakuragi02], SHCHC synthase and o-succinylbenzoic acid-CoA synthase [Johnson03] most of the enzymatic steps of the phylloquinone bisoynthesis have been determined and proven to be highly identical with those in the menaquinone biosynthesis.

About This Pathway

The enzymatic steps involved in the biosynthesis of phylloquinone in cyanobacteria and plants are similar to the biosynthetic route leading to the microbial complement menaquinone.

The discernible step between phylloquinone and menaquinone biosynthesi is the prenylation step. EC, 1,4-dioxo-2-naphthoate phytyltransferase catalyzes the attachment of a C-20 phytyl side chain leading to demethylphylloquinone [Shimada05a], whereas microbial DHNA prenyltransferases attache a multiprenyl side chain, forming demethylmenaquinones.

It has been demonstrated that the final step of the pathway, a transmethylation reaction to form phylloquinol, depends on the oxidation state of the penultimate substrate. Only this reduced (quinol) substrate is able to accept the electrons from the electrophilic S-adenosyl-L-methionine for the transmethylation. This led to the discovery that one more reaction was inserted in between demethylphylloquinone and the final product phylloquinol. This reaction is catalyzed by type II NAD(P)H dehydrogenases in both Arabidopsis thaliana and the cyanobacterium Synechocystis sp. PCC 6803 encoded by NDC1 and ndbB, respectively (now classified as EC 1.6.5.e, demethylphylloquinone reductase). Mutants lacking this enzyme accumulate demethylphylloquinone [Fatihi15].

This indicates that the pathway intermediates prior to this step are in the quinone form, since they require reduction by EC 1.6.5.e, demethylphylloquinone reductase. Thus 1,4-dihydroxy-2-naphthoate, or an earlier intermediate, must be oxidized to a qunone form such as 1,4-diketo-2-naphthoate by an unknown process prior to the phytyl chain attachment.

In general, the intermediates of the phylloquinol biosynthesis including in-feeding pathways such as 1,4-dihydroxy-2-naphthoate biosynthesis are depicted in their dihydroxy conformation, for example see 1,4-dihydroxy-2-naphthoate and 1,4-dihydroxy-2-naphthoyl-CoA, although the latter has been shown to be used in vitro in its diketo form [Widhalm09]. However, the study on the dehydrogenases of Arabidopsis and Synechocystis provide evidence that demethylphylloquinone and probably any other preceding intermediates occur in their diketo instead of the dihydroxy form [Basset15].

Citations: [Heide82a, Kolkmann87, Simantiras89, Simantiras91]

Superpathways: superpathway of phylloquinol biosynthesis

Unification Links: AraCyc:PWY-5027

Created 03-Nov-2005 by Foerster H, TAIR
Revised 23-Jul-2015 by Foerster H, Boyce Thompson Institute


Almquist75: Almquist HJ (1975). "The early history of vitamin K." Am J Clin Nutr 28(6);656-9. PMID: 805522

Basset15: Basset GJ (2015). personal communication 2015.

Collins81: Collins MD, Jones D (1981). "Distribution of isoprenoid quinone structural types in bacteria and their taxonomic implication." Microbiol Rev 45(2);316-54. PMID: 7022156

Dam35: Dam, H. (1935). "The antihaemorrhagic vitamin of the chick: occurrence and chemical nature." Nature 135:652-653.

Fatihi15: Fatihi A, Latimer S, Schmollinger S, Block A, Dussault PH, Vermaas WF, Merchant SS, Basset GJ (2015). "A Dedicated Type II NADPH Dehydrogenase Performs the Penultimate Step in the Biosynthesis of Vitamin K1 in Synechocystis and Arabidopsis." Plant Cell 27(6);1730-41. PMID: 26023160

Fujimoto12: Fujimoto N., Kosaka T., Yamada M. (2012). "Menaquinone as Well as Ubiquinone as a Crucial Component in the Escherichia coli Respiratory Chain." Chapter 10 in Chemical Biology, edited by D Ekinci, ISBN 978-953-51-0049-2.

Heide82a: Heide L, Kolkmann R, Arendt S, Leistner E (1982). "Enzymic synthesis of o-succinylbenzoyl-CoA in cell-free extracts of anthraquinone producing Galium mollugo L. cell suspension cultures." Plant Cell Reports, 1, 180-182.

Johnson00: Johnson TW, Shen G, Zybailov B, Kolling D, Reategui R, Beauparlant S, Vassiliev IR, Bryant DA, Jones AD, Golbeck JH, Chitnis PR (2000). "Recruitment of a foreign quinone into the A(1) site of photosystem I. I. Genetic and physiological characterization of phylloquinone biosynthetic pathway mutants in Synechocystis sp. pcc 6803." J Biol Chem 275(12);8523-30. PMID: 10722690

Johnson01b: Johnson TW, Zybailov B, Jones AD, Bittl R, Zech S, Stehlik D, Golbeck JH, Chitnis PR (2001). "Recruitment of a foreign quinone into the A1 site of photosystem I. In vivo replacement of plastoquinone-9 by media-supplemented naphthoquinones in phylloquinone biosynthetic pathway mutants of Synechocystis sp. PCC 6803." J Biol Chem 276(43);39512-21. PMID: 11470786

Johnson03: Johnson TW, Naithani S, Steward Jr C, Zybailov B, Jones AD, Golbeck JH, Chitnis PR (2003). "The menD and menE homologs code for 2-succinyl-6-hydroxyl-2, 4-cyclohexadiene-1-carboxylate synthase and O-succinylbenzoic acid-CoA synthase in the phylloquinone biosynthetic pathway of Synechocystis sp. PCC 6803." Biochimica et Biophysica Acta, 1557, 67-76.

Kolkmann87: Kolkmann R, Leistner E (1987). "4-2'-(carboxyphenyl)-4-oxobutyryl coenzyme A ester, an intermediate in vitamin K (menaquinone) biosynthesis." Z. Naturforsch., 42c, 1207-1214.

Sakuragi02: Sakuragi Y, Zybailov B, Shen G, Jones AD, Chitnis PR, van der Est A, Bittl R, Zech S, Stehlik D, Golbeck JH, Bryant DA (2002). "Insertional inactivation of the menG gene, encoding 2-phytyl-1,4-naphthoquinone methyltransferase of Synechocystis sp. PCC 6803, results in the incorporation of 2-phytyl-1,4-naphthoquinone into the A(1) site and alteration of the equilibrium constant between A(1) and F(X) in photosystem I." Biochemistry 41(1);394-405. PMID: 11772039

Sakuragi05: Sakuragi Y, Zybailov B, Shen G, Bryant DA, Golbeck JH, Diner BA, Karygina I, Pushkar Y, Stehlik D (2005). "Recruitment of a foreign quinone into the A1 site of photosystem I. Characterization of a menB rubA double deletion mutant in Synechococcus sp. PCC 7002 devoid of FX, FA, and FB and containing plastoquinone or exchanged 9,10-anthraquinone." J Biol Chem 280(13);12371-81. PMID: 15681848

Sharma96: Sharma V, Hudspeth ME, Meganathan R (1996). "Menaquinone (vitamin K2) biosynthesis: localization and characterization of the menE gene from Escherichia coli." Gene 1996;168(1);43-8. PMID: 8626063

Shimada01: Shimada H, Shida Y, Nemoto N, Oshima T, Yamagishi A (2001). "Quinone profiles of Thermoplasma acidophilum HO-62." J Bacteriol 183(4);1462-5. PMID: 11157962

Shimada05a: Shimada H, Ohno R, Shibata M, Ikegami I, Onai K, Ohto MA, Takamiya K (2005). "Inactivation and deficiency of core proteins of photosystems I and II caused by genetical phylloquinone and plastoquinone deficiency but retained lamellar structure in a T-DNA mutant of Arabidopsis.." Plant J 41(4);627-37. PMID: 15686525

Simantiras89: Simantiras M, Leistner E (1989). "Formation of o-succinylbenzoic acid from iso-chorismic acid in protein extracts from anthraquinone-producing plant cell suspension cultures." Phytochemistry, 28, 1381-1382.

Simantiras91: Simantiras M, Leistner E (1991). "Cell free synthesis of O-succinylbenzoic acid in protein extracts from anthraquinone and phylloquinone (vitamin K1) producing plant cell suspension cultures. Occurrence of intermediates between isochorismic and O-succinylbenzoic acid." Z. Naturforsch., 46c, 364-370.

Widhalm09: Widhalm JR, van Oostende C, Furt F, Basset GJ (2009). "A dedicated thioesterase of the Hotdog-fold family is required for the biosynthesis of the naphthoquinone ring of vitamin K1." Proc Natl Acad Sci U S A 106(14);5599-603. PMID: 19321747

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

Austin06: Austin JR, Frost E, Vidi PA, Kessler F, Staehelin LA (2006). "Plastoglobules are lipoprotein subcompartments of the chloroplast that are permanently coupled to thylakoid membranes and contain biosynthetic enzymes." Plant Cell 18(7);1693-703. PMID: 16731586

Carrie08: Carrie C, Murcha MW, Kuehn K, Duncan O, Barthet M, Smith PM, Eubel H, Meyer E, Day DA, Millar AH, Whelan J (2008). "Type II NAD(P)H dehydrogenases are targeted to mitochondria and chloroplasts or peroxisomes in Arabidopsis thaliana." FEBS Lett 582(20);3073-9. PMID: 18703057

Kaneko96: Kaneko T, Sato S, Kotani H, Tanaka A, Asamizu E, Nakamura Y, Miyajima N, Hirosawa M, Sugiura M, Sasamoto S, Kimura T, Hosouchi T, Matsuno A, Muraki A, Nakazaki N, Naruo K, Okumura S, Shimpo S, Takeuchi C, Wada T, Watanabe A, Yamada M, Yasuda M, Tabata S (1996). "Sequence analysis of the genome of the unicellular cyanobacterium Synechocystis sp. strain PCC6803. II. Sequence determination of the entire genome and assignment of potential protein-coding regions." DNA Res 1996;3(3);109-36. PMID: 8905231

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

Mutwil08: Mutwil M, Obro J, Willats WG, Persson S (2008). "GeneCAT--novel webtools that combine BLAST and co-expression analyses." Nucleic Acids Res 36(Web Server issue);W320-6. PMID: 18480120

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
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