Is there anyone discovered new drugs by actively create mutations in drug-producing organism?

Question

Recently I was reading about drug discovery.As far as I know, there are currently 2 sources of creating new compounds by:- Screening from natural sources.- Synthesizing by add/remove/replace-ing the functional groups of a known compound using chemical processes.On the other hand, molecular pharming is the process of producing drugs by integrating the drug-encoding genes into bacterial (typically E. coli) genome.I came up with the idea that if we create mutations in these drug-producing colonies, by UV light for example, eventually by chance we can obtain some new compounds once the mutations occur in the drug-encoding region or related genes.I want to search in the previous studies for those who has come up with this idea already, I tried with several keywords and there's no luck.I would want to ask is this idea practically possible? How high is the chance of having new compounds compare to screening natural sources and chemical systhesis? And if someone has already done this study, can you please provide me some references on this matter?

Answer 1

The idea is plausible but the reason there are drug encoding genes is because someone identified the genetic sequence as promising drug target. IF you change the sequence in that gene, you have essentially started over and it is just a sequence without any literature behind it. There may not be any viable drug targets since you messed the sequence up.

Identifying a drug associated sequence means that the molecules encoded by that sequence produce something that has drug activity. If you change the sequence the drug activity is not established and for all practical purposes, lost. You would be making new compounds randomly and they need to be reevaluated.