The Aflatoxin Challenge Returns!
The Aflatoxin Challenge is back! Since we left off last November, the Siegel Lab at UC Davis has been hard at work testing designs from Foldit players. Unfortunately, they ran into a major setback (all too common in scientific research), and had to go back to the drawing board to rethink their strategy. But they are back now with a new enzyme scaffold that is better suited to degrade the aflatoxin molecule, and they're asking Foldit players to redesign the enzyme so that it can bind aflatoxin more strongly!
Aflatoxin contamination in the food supply chain has resulted in health issues approaching epidemic status in developing countries, and vast food stores are deemed unsafe for consumption in regulated markets. There remain no effective means of aflatoxin removal that also maintain the food quality required for commercial products. Using modern synthetic biology tools, a UC Davis team of scientists in collaboration with the Mars Global Food Safety Center have spearheaded efforts to develop novel remediation tools.
In 2017, the Siegel Lab characterized a diverse panel of ~50 hydrolytic enzymes for expression and solubility. Then, a consortium with Mars, UC Davis, UW, Northeastern, ThermoFisher, FAO and PACA was developed around Foldit, so that citizen-scientist Foldit players might engineer new functionality into these hydrolytic enzymes and allow them to degrade the harmful aflatoxin molecule.
After the first 12 design rounds in Foldit, >500 designed proteins were tested—but not a single active enzyme was found! The UC Davis team went back and retested some fundamental assumptions that had been made when looking at the hydrolytic enzymes. They found that, at neutral pH, hydrolysis is not thermodynamically favorable for aflatoxin B1, and therefore it would have been impossible to develop a hydrolytic catalyst.
An alternative reaction
With this knowledge in hand, a new class of enzymes was targeted that catalyzes oxidative reactions, and requires nothing beyond O2. A set of ~20 diverse naturally occurring oxidative enzymes were synthesized and characterized. In initial activity screens, 2 of these were found to degrade all detectable aflatoxin. Today, we are restarting the Aflatoxin Challenge with a new Round 13 puzzle, in which players can redesign one of these active enzymes to improve hypothesized interactions with the aflatoxin molecule.
There is still a long way to go before this enzyme is efficient and specific enough for use in industrial settings. We are looking to the Foldit community to help us redesign the binding pocket. We hope Foldit players can introduce new packing interactions and hydrogen bonds with aflatoxin, to stabilize its hypothesized orientation and prime it for oxidation. We look forward to seeing what Foldit players can come up with! Play the new Aflatoxin Challenge: Round 13 puzzle now!
As in the previous aflatoxin puzzles, all Foldit player designs will be public domain. By participating in these Aflatoxin Challenge puzzles, the players agree that all player designs will be available permanently in the public domain, and the players will not seek intellectual property protection over the designs created as part of the challenge.( Posted by bkoep 82 543 | Mon, 09/30/2019 - 16:42 | 0 comments )