What is the Most Interesting Call I Have Received on NEB^® Tech Support?

Jeremy Foster, Ph.D:

A customer called tech support and their call got routed through to me because I've got some previous experience in this particular area. The customer was looking for a way to digest DNA down to single nucleotides for mass spec analysis. I was able to help them and point them towards a couple of publications, and also recommended that they actually digested to nucleosides which allows for a much more sensitive and robust mass spec analysis. And then, I also advised them on our recommendation for the cocktail of enzymes to do that job. They were quite happy with this recommendation, and when they realized that we actually had previous experience in this area, together with the necessary enzymology and the state-of-the-art mass spec instrumentation, they actually invited us to join them in a collaboration.

This turned out to be very interesting and fruitful because our collaborator had actually engineered E.coli to be able to take up nucleotide triphosphates of unnatural bases, which E-coli could then incorporate into its DNA during replication within the cell. So, our mass spec analysis actually provided definitive proof that the unnatural bases were incorporated into the DNA, and this actually led to an interesting publication in the journal, Nature, reporting the first semi-synthetic organism with an expanded genetic alphabet that went beyond the normal AGC and T bases.