Nicotine-Chomping Bacteria may hold key to Anti-Smoking Therapy

Nicotine-degrading enzyme from Pseudomonas putida, NicA2, a flavin-containing protein was studied. A kinetic evaluation of the enzyme was conducted, which included determination of Km, kcat, buffer/serum half-life, and thermostability. Additionally, the catabolism profile of NicA2 was elucidated to assess the potential toxicity of the nicotine-derived products. In characterizing the enzyme, a favorable biochemical profile of the enzyme was discovered, making NicA2 a prospective therapeutic candidate. This approach provides a new avenue for the field of nicotine addiction therapy.

This enzyme can be recreated in lab settings and possesses a number of promising characteristics for drug development. It offers a possible alternative to current smoking cessation aids, which are shown to fail in at least 80 – 90% of smokers. The idea behind an enzyme therapy would be to seek out and destroy nicotine before it reaches the brain – depriving a person of the “reward” of nicotine that can trigger relapse into smoking.

For >30 years, Janda and his colleagues have struggled to create such an enzyme in the lab, but they recently ran across a potential enzyme found in nature – NicA2 from Pseudomonas putida. It turns out this bacterium – originally isolated from soil in a tobacco field – consumes nicotine as its sole source of carbon and nitrogen.

TSRI researchers characterized the bacterial enzyme responsible for nicotine degradation and tested its potential usefulness as a therapeutic.They first combined serum from mice with a dose of nicotine equivalent to one cigarette. When they added the enzyme, the nicotine’s half-life dropped from 2 – 3 hours to just 9 to 15 minutes. A higher dose of the enzyme – with a few chemical modifications – could reduce the half-life of nicotine even further and keep it from ever reaching the brain.

The enzyme stayed stable in the lab for > 3 weeks at 98 F, which Janda said was “pretty remarkable.” Importantly, the researchers detected no toxic metabolites produced when the enzyme degraded nicotine.

Next step is to alter the enzyme’s bacterial makeup, which will help mitigate potential immune liabilities and maximize its therapeutic potential.
“Hopefully we can improve its serum stability with our future studies so that a single injection may last up to a month,” added Xue. http://www.scripps.edu/news/press/2015/20150806janda.html