If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: superpathway of phylloquinone biosynthesis
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Quinol and Quinone Biosynthesis → Phylloquinol Biosynthesis|
Phylloquinone (vitamin K1, 2-methyl-3-phytyl-1,4-naphthoquinone) acts as the electron transfer cofactor A1 of photosystem I (PS I) in higher plants and cyanobacteria. In non-photosynthetic microbes the very similar compound a menaquinone plays an essential role in several anaerobic electron transport systems [Sharma96]. The chemical structure of menaquinone (vitamin K2) exhibits a partly unsaturated side chain consisting most often 7 prenyl units, whereas phylloquinone consists of a mostly saturated phytyl side chain of 4 units [Shimada05].
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 menaquinol-8 biosynthesis) [Sharma96]. With the isolation and functional confirmation of the homolog genes in Synechocystis encoding for 1,4-dihydroxy-2-naphthoate phytyltransferase, naphthoyl-CoA synthase [Johnson00], 2-phytyl-1,4-naphthoquinone methyltransferase [Sakuragi02], 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase and O-succinylbenzoate 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.
The biosynthesis of certain components of the multienzyme complex PS I (such as phylloquinone) in cyanobacteria and plants have been found to follow analogous routes, including corresponding enzymatic activities [Heide82a] [Kolkmann87, Simantiras89, Simantiras91], reflecting the phylogenetic origin of PS I in photosynthetic microbes.
About This Pathway
The enzymatic steps involved in the biosynthesis of phylloquinone in cyanobacteria and plants are almost identical to the biosynthetic route leading to the microbial complement menaquinone. The discernible step between phylloquinone and menaquinone biosynthesis is the prenylation of 1,4-dihydroxy-2-naphthoate (DHNA). The DHNA phytyltransferase catalyzes the attachment of a C-20 phytyl side chain leading to demethylphylloquinone [Shimada05], whereas microbial DHNA prenyltransferases attache a multiprenyl side chain, forming demethylmenaquinones. The length of the side chain varies among different species.
It has been found that phylloquinone is not absolutely required for efficient electron transfer in PS I [Johnson00]. At least 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 both Arabidopsis and Synechocystis sp. PCC 6803 mutants, the deficiency of phylloquinone causes distortions in the thylakoid structure of chloroplasts, decreases the content of PS I, and affects the functionality of PS II [Shimada05].
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. This led to the discovery that one more reaction was inserted in between demethylphylloquinone and the final product phylloquinol. This reaction was 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, which resulted in the formation of the reduced demethylphylloquinol [Fatihi15]. Only this reduced (quinol) substrate was able to accept the electrons from the electrophilic S-adenosyl-L-methionine for the subsequent transmethylation step of the phylloquinol biosynthesis to yield phylloquinol [Fatihi15]. 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].
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.
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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.
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
Shimada05: 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.
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Daruwala97: Daruwala R, Bhattacharyya DK, Kwon O, Meganathan R (1997). "Menaquinone (vitamin K2) biosynthesis: overexpression, purification, and characterization of a new isochorismate synthase from Escherichia coli." J Bacteriol 1997;179(10);3133-8. PMID: 9150206
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