Active site alanine preceding catalytic cysteine determines unique substrate specificity in bacterial CoA-acylating prenal dehydrogenase

FEBS Letters
Ellen BecherJessica Purswani

Abstract

In detoxification and fermentation processes, acylating dehydrogenases catalyze the reversible oxidation of aldehydes to their corresponding acyl-CoA esters. Here, we characterize an enzyme from Aquincola tertiaricarbonis L108 responsible for prenal (3-methyl-2-butenal) to 3-methylcrotonyl-CoA oxidation. Enzyme kinetics demonstrate a preference for C5 substrates not yet observed in aldehyde dehydrogenases. Compared to acetaldehyde and acetyl-CoA, conversion of valeraldehyde and valeryl-CoA is > 100- and 8-fold more efficient, respectively. Enzyme variants with A254I, A254P, and A254G mutations indicate that active site Ala preceding the catalytic C255 is crucial for this unique specificity. These results shed new light on evolutionary adaptation of aldehyde dehydrogenases toward xenobiotics and structure-guided design of highly specific enzymes for production of biofuels, such as linear or iso-branched butanols and pentanols.

References

Sep 1, 1990·Applied and Environmental Microbiology·R T Yan, J S Chen
Nov 1, 1971·Journal of Bacteriology·J P Salanitro, W S Wegener
Feb 7, 1997·The Journal of Biological Chemistry·B X Yan, Y Q Sun
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Apr 26, 2005·Nucleic Acids Research·Yang Zhang, Jeffrey Skolnick
Jun 7, 2007·International Journal of Systematic and Evolutionary Microbiology·Ute LechnerThore Rohwerder
Mar 2, 2011·Nature Chemical Biology·Brooks B Bond-WattsMichelle C Y Chang
Oct 13, 2011·Molecular Systems Biology·Fabian SieversDesmond G Higgins
Jun 27, 2012·Microbial Cell Factories·Gabriel M Rodriguez, Shota Atsumi
Oct 17, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hsien-Chung Tseng, Kristala L J Prather
Jun 6, 2013·Nucleic Acids Research·Lim HeoChaok Seok
Apr 23, 2014·Nucleic Acids Research·Xavier Robert, Patrice Gouet
May 2, 2014·Nucleic Acids Research·Marco BiasiniTorsten Schwede
Apr 23, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dominik M PeterTobias J Erb
Oct 26, 2016·Protein Science : a Publication of the Protein Society·Jonathan ExtanceSusan J Crennell

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Protein Structures

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Bacterial Protein Structures (ASM)

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Biofuels (ASM)

Biofuels are produced through contemporary processes from biomass rather than geological processes involved in fossil fuel formation. Examples include biodiesel, green diesel, biogas, etc. Discover the latest research on biofuels in this feed.

Related Papers

Advances in Experimental Medicine and Biology
P NinfaliM Magnani
Enzyme Research
Sulaiman Al-ZuhairLucia Gardossi
Advances in Experimental Medicine and Biology
R PietruszkoT Lehmann
Expert Opinion on Drug Metabolism & Toxicology
Satori A MarchittiVasilis Vasiliou
© 2022 Meta ULC. All rights reserved