Rational Design of a Flavoenzyme for Aerobic Nicotine Catabolism
Xu, P.; Tang, H.; Hu, H.; Xu, Z.; Zhang, Z.; Stull, F.; Song, P.
Show abstract
Enzymatic therapy with nicotine-degrading enzyme is a new strategy in treating nicotine addiction, which can reduce nicotine concentrations and weaken withdrawal in the rat model. However, when O2 is used as the electron acceptor, no satisfactory performance has been achieved with one of the most commonly studied and efficient nicotine-catabolizing enzymes, NicA2. To obtain more efficient nicotine-degrading enzyme, we rationally designed and engineered a flavoenzyme Pnao, which shares high structural similarity with NicA2 (RMSD = 1.143 [A]) and efficiently catalyze pseudooxynicotine into 3-succinoyl-semialdehyde pyridine using O2. Through amino acid alterations with NicA2, five Pnao mutants were generated, which can degrade nicotine in Tris-HCl buffer and retained catabolic activity on its natural substrate. Nicotine-1-N-oxide was identified as one of the reaction products. Four of the derivative mutants showed activity in rat serum and Trp220 and Asn224 were found critical for enzyme specificity. Our findings offer a novel avenue for research into aerobic nicotine catabolism and provides a promising method of generating additional nicotine-catalytic enzymes.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Biosynthesis of novel desferrioxamine derivatives requires unprecedented crosstalk between separate NRPS-independent siderophore pathways 94%
- Bacterial catabolic system of acetovanillone and acetosyringone useful for upgrading aromatic compounds obtained through chemical lignin depolymerization 94%
- Biodegradation of the endocrine-disrupting compound bisphenol F by Sphingobium yanoikuyae DN12 94%
Similar papers in this journal
- Structure and evolution of Alanine/Serine Decarboxylases and the engineering of theanine production 95%
- Growth inhibitory factor/metallothionein-3 is a sulfane sulfur-binding protein 94%
- Targeting SLC7A11-mediated cysteine metabolism for the treatment of trastuzumab resistant HER2 positive breast cancer 93%
Similar papers in this journal
Similar papers in this journal
- Unleashing the Potential of Noncanonical Amino Acid Biosynthesis for Creation of Cells with Site-Specific Tyrosine Sulfation 94%
- An iron (II) dependent oxygenase performs the last missing step of plant lysine catabolism 94%
- Harnessing Protein Language Model for Structure-Based Discovery of Highly Efficient and Robust PET Hydrolases 93%
Similar papers in this journal
- More than just an Eagle Killer: The freshwater cyanobacterium Aetokthonos hydrillicola produces highly toxic dolastatin derivatives 94%
- Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins 94%
- Enzymatic carbon-fluorine bond cleavage by human gut microbes 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.