Bacterial Aryl Sulfotransferases in Selective and Sustainable Sulfation of Biologically Active Compounds using Novel Sulfate Donors

0561642 - MBÚ 2023 RIV DE eng J - Journal Article
Brodsky, Katerina - Káňová, Kristýna - Konvalinková, Dorota - Slámová, Kristýna - Pelantová, Helena - Valentová, Kateřina - Bojarová, Pavla - Křen, Vladimír - Petrásková, Lucie
Bacterial Aryl Sulfotransferases in Selective and Sustainable Sulfation of Biologically Active Compounds using Novel Sulfate Donors.
ChemSusChem. Roč. 15, č. 18 (2022), č. článku e202201253. ISSN 1864-5631. E-ISSN 1864-564X
R&D Projects: GA ČR(CZ) GA19-00043S
Institutional support: RVO:61388971
Keywords : aryl sulfotransferase * biocatalysis * enzyme catalysis * leaving group * sulfation
OECD category: Biochemistry and molecular biology
Impact factor: 8.4, year: 2022
Method of publishing: Limited access
https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cssc.202201253

Regioselective sulfation of bioactive compounds is a vital and scarcely studied topic in enzyme-catalyzed transformations and metabolomics. The major bottleneck of enzymatic sulfation consists in finding suitable sulfate donors. In this regard, 3 '-phosphoadenosine 5 '-phosphosulfate (PAPS)-independent aryl sulfotransferases using aromatic sulfate donors are a favored choice due to their cost-effectiveness. This work presents a unique study of five sulfate donors differing in their leaving group pK(a) values with a new His-tagged construct of aryl sulfotransferase from Desulfitobacterium hafniense (DhAST-tag). DhAST-tag was purified to homogeneity and biochemically characterized. Two new donors (3-nitrophenyl sulfate and 2-nitrophenyl sulfate) were synthesized. The kinetic parameters of these and other commercial sulfates (4-nitrophenyl, 4-methylumbelliferyl, and phenyl) revealed large differences with respect to the structure of the leaving group. These donors were screened for the sulfation of selected flavonoids (myricetin, chrysin) and phenolic acids (gallate, 3,4-dihydroxyphenylacetate). The donor impact on the sulfation regioselectivity and yield was assessed. The obtained regioselectively sulfated compounds are authentic human metabolites required as standards in clinical trials.
Permanent Link: https://hdl.handle.net/11104/0335024