“I think it’s very nice work,” says Xi Chen, a chemist at the University of California, Davis, whose group uses enzymatic techniques to synthesize carbohydrates. For complicated compounds like enterocin, “a lot of enzymes are involved in the process, so it’s been very difficult to get individual enzymes out and put them together for making the product,” Chen says. Moore and his colleagues had worked out the biosynthetic pathway in the S. maritimus, so they knew the steps involved.
Another way to produce enterocin would be to genetically engineer a microorganism with that pathway–a familiar method in drug manufacturing. But putting that process in a flask “allows you to tinker more,” Moore says. For example, the enzymes or starting materials can easily be changed, yielding a library of different products. That flexibility makes the method a valuable tool for discovery.
Scott Snyder, a synthetic-organic chemist at Columbia University, was impressed by the enzymatic method’s ability to do a particular reaction known as a Favorskii rearrangement. “If we were to attempt this in a flask with the standard reagents you would utilize to do this, there is no way one would get the selectivity leading to enterocin as the final product,” he says. “It’s mechanistically quite complicated.”
Snyder sees synthetic methods based on enzymes ultimately complementing organic synthesis methods. “If it’s easy to alter an enzyme to create a desired analog, then an enzymatic pathway would provide a full solution,” he says. “But if that doesn’t exist, then you need someone to come in with a more traditional approach to make that compound.”