Bioorganic Chemistry p. 380 - 393 (2006)
Update date:2022-08-28
Topics:
Baykal, Ahmet
Chakraborty, Sumit
Dodoo, Afua
Jordan, Frank
In addition to the decarboxylation of 2-oxo acids, thiamin diphosphate (ThDP)-dependent decarboxylases/dehydrogenases can also carry out so-called carboligation reactions, where the central ThDP-bound enamine intermediate reacts with electrophilic substrates. For example, the enzyme yeast pyruvate decarboxylase (YPDC, from Saccharomyces cerevisiae) or the E1 subunit of the Escherichia coli pyruvate dehydrogenase complex (PDHc-E1) can produce acetoin and acetolactate, resulting from the reaction of the central thiamin diphosphate-bound enamine with acetaldehyde and pyruvate, respectively. Earlier, we had shown that some active center variants indeed prefer such a carboligase pathway to the usual one [Sergienko, Jordan, Biochemistry 40 (2001) 7369-7381; Nemeria et al., J. Biol. Chem. 280 (2005) 21,473-21,482]. Herein is reported detailed analysis of the stereoselectivity for forming the carboligase products acetoin, acetolactate, and phenylacetylcarbinol by the E477Q and D28A YPDC, and the E636A and E636Q PDHc-E1 active-center variants. Both pyruvate and β-hydroxypyruvate were used as substrates and the enantiomeric excess was analyzed by a combination of NMR, circular dichroism and chiral-column gas chromatographic methods. Remarkably, the two enzymes produced a high enantiomeric excess of the opposite enantiomer of both acetoin-derived and acetolactate-derived products, strongly suggesting that the facial selectivity for the electrophile in the carboligation is different in the two enzymes. The different stereoselectivities exhibited by the two enzymes could be utilized in the chiral synthesis of important intermediates.
View MoreContact:0519-85170101-802
Address:Fifth Floor,B of Beihua Buliding,520 Road of Science and Education City,Changwu middle road NO.801,Wujin District,Changzhou,Jiangsu province
Contact:0086-27-83607103/83642615
Address:No.498, Jianshe Ave, Wuhan, China
Contact:86-21-57725962
Address:shanghai
shanghai tuomiao chemicial co.,ltd.
website:https://www.tuomiaochem.com/
Contact:021 - 59853336
Address:shanghai
Shanghai Yuanding Chem. Sci. & Tech. Co., Ltd.
website:http://www.shydtec.com
Contact:86-21-57721279
Address:Science and Technology Park, Songjiang District, Shanghai, China
Doi:10.1002/aoc.3990
(2018)Doi:10.1021/ja01151a520
(1951)Doi:10.1021/ol052725j
(2006)Doi:10.1039/c4ob02483d
(2015)Doi:10.1016/S0040-4039(01)86165-7
(1979)Doi:10.1002/anie.200805427
(2009)