A Multi-enzyme Cascade for the Biosynthesis of AICA Ribonucleoside Di- and Triphosphate.
Acinetobacter
/ enzymology
Adenine Phosphoribosyltransferase
/ metabolism
Aminoimidazole Carboxamide
/ analogs & derivatives
Bacteria
/ enzymology
Escherichia coli
/ enzymology
Hydrogen-Ion Concentration
Phosphotransferases (Phosphate Group Acceptor)
/ metabolism
Polyphosphates
/ chemistry
Ribonucleotides
/ biosynthesis
Temperature
adenine phosphoribosyltransferase
enzymatic nucleotide synthesis
enzyme cascades
nucleotide analogues
polyphosphate kinases
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
04 02 2022
04 02 2022
Historique:
revised:
01
12
2021
received:
31
10
2021
pubmed:
4
12
2021
medline:
9
3
2022
entrez:
3
12
2021
Statut:
ppublish
Résumé
AICA (5'-aminoimidazole-4-carboxamide) ribonucleotides with different phosphorylation levels are the pharmaceutically active metabolites of AICA nucleoside-based drugs. The chemical synthesis of AICA ribonucleotides with defined phosphorylation is challenging and expensive. In this study, we describe two enzymatic cascades to synthesize AICA derivatives with defined phosphorylation levels from the corresponding nucleobase and the co-substrate phosphoribosyl pyrophosphate. The cascades are composed of an adenine phosphoribosyltransferase from Escherichia coli (EcAPT) and different polyphosphate kinases: polyphosphate kinase from Acinetobacter johnsonii (AjPPK), and polyphosphate kinase from Meiothermus ruber (MrPPK). The role of the EcAPT is to bind the nucleobase to the sugar moiety, while the kinases are responsible for further phosphorylation of the nucleotide to produce the desired phosphorylated AICA ribonucleotide. The selected enzymes were characterized, and conditions were established for two enzymatic cascades. The diphosphorylated AICA ribonucleotide derivative ZDP, synthesized from the cascade EcAPT/AjPPK, was produced with a conversion up to 91 %. The EcAPT/MrPPK cascade yielded ZTP with conversion up to 65 % with ZDP as a side product.
Identifiants
pubmed: 34859954
doi: 10.1002/cbic.202100596
pmc: PMC9299608
doi:
Substances chimiques
Polyphosphates
0
Ribonucleotides
0
Aminoimidazole Carboxamide
360-97-4
Adenine Phosphoribosyltransferase
EC 2.4.2.7
Phosphotransferases (Phosphate Group Acceptor)
EC 2.7.4.-
polyphosphate kinase
EC 2.7.4.1
AICA ribonucleotide
F0X88YW0YK
triphosphoric acid
NU43IAG5BC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202100596Subventions
Organisme : Deustche Forschungsgemeinschaft (DFG)
ID : LO 2678/2-1
Informations de copyright
© 2021 The Authors. ChemBioChem published by Wiley-VCH GmbH.
Références
Nat Rev Drug Discov. 2019 Jul;18(7):527-551
pubmed: 30867601
Eur J Biochem. 1995 Apr 15;229(2):558-65
pubmed: 7744080
Biotechnol Adv. 2015 Sep-Oct;33(5):412-34
pubmed: 25795057
Oncogenesis. 2016 Jan 18;5:e188
pubmed: 26779810
J Am Chem Soc. 2007 Mar 21;129(11):3426-32
pubmed: 17326637
Biochim Biophys Acta. 2011 Jun;1807(6):707-18
pubmed: 21692240
Chem Commun (Camb). 2015 Apr 7;51(27):5798-811
pubmed: 25654472
J Biol Chem. 2000 Jul 7;275(27):20231-4
pubmed: 10816600
Org Biomol Chem. 2009 May 7;7(9):1778-80
pubmed: 19590770
Appl Microbiol Biotechnol. 2015 Jun;99(11):4615-27
pubmed: 25952113
Int J Mol Sci. 2017 Nov 08;18(11):
pubmed: 29117108
Cells. 2021 May 04;10(5):
pubmed: 34064363
Biomolecules. 2021 Feb 25;11(3):
pubmed: 33668847
Appl Environ Microbiol. 2014 Apr;80(8):2602-8
pubmed: 24532069
Chem Rev. 2000 Jun 14;100(6):2047-60
pubmed: 11749283
Chembiochem. 2022 Feb 4;23(3):e202100596
pubmed: 34859954
J Bacteriol. 2004 Aug;186(15):5178-81
pubmed: 15262957
Antiviral Res. 2010 Apr;86(1):101-20
pubmed: 20417378
Front Bioeng Biotechnol. 2020 Aug 06;8:854
pubmed: 32903716
Acta Pharmacol Sin. 2007 Dec;28(12):1984-90
pubmed: 18031613
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16678-83
pubmed: 12486232
Beilstein J Org Chem. 2018 Dec 21;14:3098-3105
pubmed: 30643587
Acta Naturae. 2016 Oct-Dec;8(4):82-90
pubmed: 28050269
Appl Environ Microbiol. 2010 Mar;76(5):1462-70
pubmed: 20048065
Mol Microbiol. 2009 Dec;74(5):1187-97
pubmed: 19843229
Int J Mol Sci. 2020 Sep 16;21(18):
pubmed: 32947863
Appl Environ Microbiol. 2007 Aug;73(15):5026-33
pubmed: 17545325
J Endocrinol Invest. 2018 Nov;41(11):1275-1282
pubmed: 29546654
Chembiochem. 2019 Apr 15;20(8):1019-1022
pubmed: 30549179
Microbiol Mol Biol Rev. 2016 Dec 28;81(1):
pubmed: 28031352
Invest Ophthalmol Vis Sci. 2014 Apr 29;55(7):4175-85
pubmed: 24781943
Chem Rev. 2014 Sep 24;114(18):9154-218
pubmed: 25144792
JAMA. 1997 Jan 22-29;277(4):325-32
pubmed: 9002496
Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17730-5
pubmed: 19001261
Nucleosides Nucleotides Nucleic Acids. 2013;32(6):273-93
pubmed: 23638922
J Am Chem Soc. 2007 Dec 5;129(48):14911-21
pubmed: 17990877
Biosci Rep. 2015 Nov 18;36(1):e00294
pubmed: 26582818