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Literature summary extracted from

  • Motoyama, K.; Sobue, F.; Kawaide, H.; Yoshimura, T.; Hemmi, H.
    Conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase by single amino acid mutations (2019), Appl. Environ. Microbiol., 85, e00256-19 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.B29 recombinant expression of His-tagged E140 mutants of mevalonate 3-kinase, functioning as 5-phosphomevalonate 3-kinases, in Escherichia coli strain BL21 Thermoplasma acidophilum
2.7.1.185 gene Ta1305, the pBAD-TacM plasmid series contains the genes of M3K, M3P5K, BMD, and IPK for the expression of part of modified MVA pathway II. Although the M3K, M3P5K, and IPK genes are derived from Thermoplasma acidophilum, various BMD genes have been utilized for plasmid construction. Recombinant expression of His-tagged enzyme in Escherichia coli strain BL21 Thermoplasma acidophilum
2.7.1.186 gene Ta0762, the pBAD-TacM plasmid series contains the genes of M3K, M3P5K, BMD, and IPK for the expression of part of modified MVA pathway II. Although the M3K, M3P5K, and IPK genes are derived from Thermoplasma acidophilum, various BMD genes have been utilized for plasmid construction. Recombinant expression of His-tagged enzyme in Escherichia coli strain BL21 Thermoplasma acidophilum
2.7.4.2 gene ERG8, the pBAD plasmid containing the genes of MVK, PMK, and DMD from Saccharomyces cerevisiae (pBAD-ScMPD) is used for expression of a part of the classical MVA pathway (Fig. 6B). The codon usage of the MVK and PMK genes has been optimized for Escherichia coli, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21 Saccharomyces cerevisiae

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.1.185 analysis of the substrate-complex crystal structure of TacM3K (PDB ID 4RKS) Thermoplasma acidophilum

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.B29 additional information substrate-interacting glutamate residue E140 of Thermoplasma acidophilum mevalonate 3-kinase (EC 2.7.1.185) is replaced by smaller amino acids, including its counterparts in diphosphomevalonate decarboxylase and phosphomevalonate decarboxylase, with the aim of altering substrate specificity. These single amino acid mutations results in the conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase, which can synthesize 3,5-bisphosphomevalonate from 5-phosphomevalonate. The mutants catalyzing the hitherto undiscovered reaction enables the construction of an artificial mevalonate pathway in Escherichia coli cells, as is demonstrated by the accumulation of lycopene, a red carotenoid pigment. Alternative MVA pathway II overview. Constructed plasmids and strains, overview Thermoplasma acidophilum
2.7.1.185 E140A site-directed mutagenesis, inactive mutant Thermoplasma acidophilum
2.7.1.185 E140G site-directed mutagenesis, the mutation results in the conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase, which can synthesize 3,5-bisphosphomevalonate from 5-phosphomevalonate Thermoplasma acidophilum
2.7.1.185 E140S site-directed mutagenesis, the mutation results in the conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase, which can synthesize 3,5-bisphosphomevalonate from 5-phosphomevalonate Thermoplasma acidophilum
2.7.1.185 additional information substrate-interacting glutamate residue E140 of Thermoplasma acidophilum mevalonate 3-kinase is replaced by smaller amino acids, including its counterparts in diphosphomevalonate decarboxylase and phosphomevalonate decarboxylase, with the aim of altering substrate specificity. These single amino acid mutations results in the conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase, which can synthesize 3,5-bisphosphomevalonate from 5-phosphomevalonate. The mutants catalyzing the hitherto undiscovered reaction enables the construction of an artificial mevalonate pathway in Escherichia coli cells, as is demonstrated by the accumulation of lycopene, a red carotenoid pigment. Neither wild-type TacM3K nor any mutants show reactivity toward MVA 5-diphosphate. Alternative MVA pathway II overview. Constructed plasmids and strains, overview Thermoplasma acidophilum

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.B29 ATP + (R)-5-phosphomevalonate Thermoplasma acidophilum
-
 ADP + (R)-3,5-bisphosphomevalonate
-
 ?
2.7.1.B29 ATP + (R)-5-phosphomevalonate Thermoplasma acidophilum JCM 9062
-
 ADP + (R)-3,5-bisphosphomevalonate
-
 ?
2.7.1.B29 ATP + (R)-5-phosphomevalonate Thermoplasma acidophilum AMRC-C165
-
 ADP + (R)-3,5-bisphosphomevalonate
-
 ?
2.7.1.B29 ATP + (R)-5-phosphomevalonate Thermoplasma acidophilum ATCC 25905
-
 ADP + (R)-3,5-bisphosphomevalonate
-
 ?
2.7.1.B29 ATP + (R)-5-phosphomevalonate Thermoplasma acidophilum NBRC 15155
-
 ADP + (R)-3,5-bisphosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate Thermoplasma acidophilum
-
 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate Thermoplasma acidophilum JCM 9062
-
 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate Thermoplasma acidophilum AMRC-C165
-
 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate Thermoplasma acidophilum ATCC 25905
-
 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate Thermoplasma acidophilum NBRC 15155
-
 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.186 ATP + (R)-3-phosphomevalonate Thermoplasma acidophilum
-
 ADP + 3,5-bisphosphomevalonate
-
 ?
2.7.1.186 ATP + (R)-3-phosphomevalonate Thermoplasma acidophilum JCM 9062
-
 ADP + 3,5-bisphosphomevalonate
-
 ?
2.7.1.186 ATP + (R)-3-phosphomevalonate Thermoplasma acidophilum AMRC-C165
-
 ADP + 3,5-bisphosphomevalonate
-
 ?
2.7.1.186 ATP + (R)-3-phosphomevalonate Thermoplasma acidophilum ATCC 25905
-
 ADP + 3,5-bisphosphomevalonate
-
 ?
2.7.1.186 ATP + (R)-3-phosphomevalonate Thermoplasma acidophilum NBRC 15155
-
 ADP + 3,5-bisphosphomevalonate
-
 ?
2.7.4.2 ATP + (R)-5-phosphomevalonate Saccharomyces cerevisiae
-
 ADP + (R)-5-diphosphomevalonate
-
 ?
2.7.4.2 ATP + (R)-5-phosphomevalonate Saccharomyces cerevisiae ATCC 204508
-
 ADP + (R)-5-diphosphomevalonate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.B29 Thermoplasma acidophilum
-
-
-
2.7.1.B29 Thermoplasma acidophilum AMRC-C165
-
-
-
2.7.1.B29 Thermoplasma acidophilum ATCC 25905
-
-
-
2.7.1.B29 Thermoplasma acidophilum JCM 9062
-
-
-
2.7.1.B29 Thermoplasma acidophilum NBRC 15155
-
-
-
2.7.1.185 Thermoplasma acidophilum Q9HIN1
-
-
2.7.1.185 Thermoplasma acidophilum AMRC-C165 Q9HIN1
-
-
2.7.1.185 Thermoplasma acidophilum ATCC 25905 Q9HIN1
-
-
2.7.1.185 Thermoplasma acidophilum JCM 9062 Q9HIN1
-
-
2.7.1.185 Thermoplasma acidophilum NBRC 15155 Q9HIN1
-
-
2.7.1.186 Thermoplasma acidophilum Q9HK44
-
-
2.7.1.186 Thermoplasma acidophilum AMRC-C165 Q9HK44
-
-
2.7.1.186 Thermoplasma acidophilum ATCC 25905 Q9HK44
-
-
2.7.1.186 Thermoplasma acidophilum JCM 9062 Q9HK44
-
-
2.7.1.186 Thermoplasma acidophilum NBRC 15155 Q9HK44
-
-
2.7.4.2 Saccharomyces cerevisiae P24521
-
-
2.7.4.2 Saccharomyces cerevisiae ATCC 204508 P24521
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.1.B29 recombinant His-tagged enzymes from Escherichia coli strain BL21 by nickel affinity chromatography Thermoplasma acidophilum
2.7.1.185 recombinant His-tagged enzyme from Escherichia coli strain BL21 by nickel affinity chromatography Thermoplasma acidophilum
2.7.1.186 recombinant His-tagged enzyme from Escherichia coli strain BL21 by nickel affinity chromatography Thermoplasma acidophilum
2.7.4.2 recombinant His-tagged enzyme from Escherichia coli strain BL21 by nickel affinity chromatography Saccharomyces cerevisiae

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.B29 ATP + (R)-5-phosphomevalonate
-
 Thermoplasma acidophilum ADP + (R)-3,5-bisphosphomevalonate
-
 ?
2.7.1.B29 ATP + (R)-5-phosphomevalonate
-
 Thermoplasma acidophilum JCM 9062 ADP + (R)-3,5-bisphosphomevalonate
-
 ?
2.7.1.B29 ATP + (R)-5-phosphomevalonate
-
 Thermoplasma acidophilum AMRC-C165 ADP + (R)-3,5-bisphosphomevalonate
-
 ?
2.7.1.B29 ATP + (R)-5-phosphomevalonate
-
 Thermoplasma acidophilum ATCC 25905 ADP + (R)-3,5-bisphosphomevalonate
-
 ?
2.7.1.B29 ATP + (R)-5-phosphomevalonate
-
 Thermoplasma acidophilum NBRC 15155 ADP + (R)-3,5-bisphosphomevalonate
-
 ?
2.7.1.B29 additional information substrate specificity analysis, no reactivity toward MVA 5-diphosphate. Electrospray ionization mass spectrometry (ESI-MS) analysis of the product is performed in the negative mode using the direct infusion method Thermoplasma acidophilum ?
-
-
2.7.1.B29 additional information substrate specificity analysis, no reactivity toward MVA 5-diphosphate. Electrospray ionization mass spectrometry (ESI-MS) analysis of the product is performed in the negative mode using the direct infusion method Thermoplasma acidophilum JCM 9062 ?
-
-
2.7.1.B29 additional information substrate specificity analysis, no reactivity toward MVA 5-diphosphate. Electrospray ionization mass spectrometry (ESI-MS) analysis of the product is performed in the negative mode using the direct infusion method Thermoplasma acidophilum AMRC-C165 ?
-
-
2.7.1.B29 additional information substrate specificity analysis, no reactivity toward MVA 5-diphosphate. Electrospray ionization mass spectrometry (ESI-MS) analysis of the product is performed in the negative mode using the direct infusion method Thermoplasma acidophilum ATCC 25905 ?
-
-
2.7.1.B29 additional information substrate specificity analysis, no reactivity toward MVA 5-diphosphate. Electrospray ionization mass spectrometry (ESI-MS) analysis of the product is performed in the negative mode using the direct infusion method Thermoplasma acidophilum NBRC 15155 ?
-
-
2.7.1.185 ATP + (R)-mevalonate
-
 Thermoplasma acidophilum ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate
-
 Thermoplasma acidophilum JCM 9062 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate
-
 Thermoplasma acidophilum AMRC-C165 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate
-
 Thermoplasma acidophilum ATCC 25905 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate
-
 Thermoplasma acidophilum NBRC 15155 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 additional information substrate specificity, overview Thermoplasma acidophilum ?
-
-
2.7.1.185 additional information substrate specificity, overview Thermoplasma acidophilum JCM 9062 ?
-
-
2.7.1.185 additional information substrate specificity, overview Thermoplasma acidophilum AMRC-C165 ?
-
-
2.7.1.185 additional information substrate specificity, overview Thermoplasma acidophilum ATCC 25905 ?
-
-
2.7.1.185 additional information substrate specificity, overview Thermoplasma acidophilum NBRC 15155 ?
-
-
2.7.1.186 ATP + (R)-3-phosphomevalonate
-
 Thermoplasma acidophilum ADP + 3,5-bisphosphomevalonate
-
 ?
2.7.1.186 ATP + (R)-3-phosphomevalonate
-
 Thermoplasma acidophilum JCM 9062 ADP + 3,5-bisphosphomevalonate
-
 ?
2.7.1.186 ATP + (R)-3-phosphomevalonate
-
 Thermoplasma acidophilum AMRC-C165 ADP + 3,5-bisphosphomevalonate
-
 ?
2.7.1.186 ATP + (R)-3-phosphomevalonate
-
 Thermoplasma acidophilum ATCC 25905 ADP + 3,5-bisphosphomevalonate
-
 ?
2.7.1.186 ATP + (R)-3-phosphomevalonate
-
 Thermoplasma acidophilum NBRC 15155 ADP + 3,5-bisphosphomevalonate
-
 ?
2.7.4.2 ATP + (R)-5-phosphomevalonate
-
 Saccharomyces cerevisiae ADP + (R)-5-diphosphomevalonate
-
 ?
2.7.4.2 ATP + (R)-5-phosphomevalonate
-
 Saccharomyces cerevisiae ATCC 204508 ADP + (R)-5-diphosphomevalonate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.1.185 M3K
-
 Thermoplasma acidophilum
2.7.1.185 mevalonate 3-kinase
-
 Thermoplasma acidophilum
2.7.1.185 Ta1305
-
 Thermoplasma acidophilum
2.7.1.185 TacM3K
-
 Thermoplasma acidophilum
2.7.1.186 M3P5K
-
 Thermoplasma acidophilum
2.7.1.186 MVA-3-P 5-kinase
-
 Thermoplasma acidophilum
2.7.1.186 Ta0762
-
 Thermoplasma acidophilum
2.7.4.2 ERG8
-
 Saccharomyces cerevisiae
2.7.4.2 PMK
-
 Saccharomyces cerevisiae

General Information

EC Number General Information Comment Organism
2.7.1.B29 physiological function a substrate-interacting glutamate residue of Thermoplasma acidophilum mevalonate 3-kinase (EC 2.7.1.185) is replaced by smaller amino acids, including its counterparts in diphosphomevalonate decarboxylase and phosphomevalonate decarboxylase, with the aim of altering substrate specificity. These single amino acid mutations E140S and E140G result in the conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase, which can synthesize 3,5-bisphosphomevalonate from 5-phosphomevalonate. The mutants catalyzing the hitherto undiscovered reaction enables the construction of an artificial mevalonate pathway in Escherichia coli cells, as is demonstrated by the accumulation of lycopene, a red carotenoid pigment Thermoplasma acidophilum
2.7.1.185 evolution mevalonate 3-kinase is an enzyme involved in the modified mevalonate pathway specific to limited species of thermophilic archaea Thermoplasma acidophilum
2.7.1.185 metabolism mevalonate 3-kinase plays a key role in a recently discovered modified mevalonate pathway specific to thermophilic archaea of the order Thermoplasmatales, pathway overview. In the pathway called modified MVA pathway II, mevalonate (MVA) is phosphorylated at the 3-hydroxyl group to yield 3-phosphomevalonate (MVA-3-P) by the action of mevalonate 3-kinase (M3K) rather than at the 5-hydroxyl group as in the reaction of MVK (EC 2.7.4.2). M3K is also homologous to diphosphomevalonate decarboxylase (DMD, EC 4.1.1.33). After the formation of MVA-3-P, another kinase, MVA-3-P 5-kinase (M3P5K), catalyzes its 5-phosphorylation, and a subsequent decarboxylation is catalyzed by another DMD homologue, 3,5-bisphosphomevalonate decarboxylase (BMD), to give isopentenyl phosphate (IP). IP is then phosphorylated by isopentenyl phosphate kinase (IPK) to yield isopentenyl diphosphate (IPP). The M3K enzyme is homologous to diphosphomevalonate decarboxylase, which is involved in the widely distributed classical mevalonate pathway, and to phosphomevalonate decarboxylase, which is possessed by halophilic archaea and some Chloroflexi bacteria. Neither wild-type TacM3K nor any mutants show reactivity toward MVA 5-diphosphate Thermoplasma acidophilum
2.7.1.185 additional information comparison between the substrate-complex crystal structure of TacM3K (PDB ID 4RKS) and that of Sulfolobus solfataricus DMD (SsoDMD, PDB ID 5GMD) revealing interesting differences in the structures of the active sites. The steric hindrance introduced by Glu140 seems responsible for excluding larger substrates, such as MVA 5-phosphate and MVA 5-diphosphate, from the active site of TacM3K Thermoplasma acidophilum
2.7.1.185 physiological function mevalonate 3-kinase catalyzes the ATP-dependent 3-phosphorylation of mevalonate but does not catalyze the subsequent decarboxylation as related decarboxylases do Thermoplasma acidophilum
2.7.1.186 evolution mevalonate 3-phosphate 5-kinase is an enzyme involved in the modified mevalonate pathway specific to limited species of thermophilic archaea Thermoplasma acidophilum
2.7.1.186 metabolism mevalonate 3-kinase plays a key role in a recently discovered modified mevalonate pathway specific to thermophilic archaea of the order Thermoplasmatales, pathway overview. In the pathway called modified MVA pathway II, mevalonate (MVA) is phosphorylated at the 3-hydroxyl group to yield 3-phosphomevalonate (MVA-3-P) by the action of mevalonate 3-kinase (M3K, EC 2.7.1.185) rather than at the 5-hydroxyl group as in the reaction of MVK (EC 2.7.4.2). M3K is also homologous to diphosphomevalonate decarboxylase (DMD). After the formation of MVA-3-P, another kinase, MVA-3-P 5-kinase (M3P5K), catalyzes its 5-phosphorylation, and a subsequent decarboxylation is catalyzed by another DMD homologue, 3,5-bisphosphomevalonate decarboxylase (BMD), to give isopentenyl phosphate (IP). IP is then phosphorylated by isopentenyl phosphate kinase (IPK) to yield isopentenyl diphosphate (IPP) Thermoplasma acidophilum
2.7.1.186 physiological function mevalonate 3-phosphate 5-kinase catalyzes the ATP-dependent 5-phosphorylation of 3-phosphomevalonate Thermoplasma acidophilum
2.7.4.2 metabolism almost all eukaryotes, most of the MVA pathway-utilizing bacteria, and the archaea of the order Sulfolobales utilize mevalonate kinase (MVK), phosphomevalonate kinase (PMK), and diphosphomevalonate decarboxylase (DMD) for that purpose. The pathway that includes this set of enzymes is called the classical MVA pathway because it was discovered more than half a century ago Saccharomyces cerevisiae
2.7.4.2 physiological function mevalonate 3-kinase catalyzes the ATP-dependent 3-phosphorylation of mevalonate but does not catalyze the subsequent decarboxylation as related decarboxylases do Saccharomyces cerevisiae