Re: How does oligomycin affect both bacteria and human cells?

Dear Neha,

Thanks for the question. I'm not surprised that you had trouble locating information about oligomycin, because the data that you were looking for are very specialist and technical. I searched the web with every search engine that I know of and I couldn't find very much either. In the end I had to look in some very specialist journals with names like "Journal of Antibiotics" and "Tetrahedron Letters" to find the information.

OK. First you ask, how does oligomycin affect cells? I wonder if I should be telling you this-is part of the project not to find out how oligomycin works? :-) The simple answer is that oligomycin inhibits an enzyme called ATP synthase. This is the enzyme that makes ATP, the chemical that all cells use for energy. The enzyme is made up of 2 major parts, and if I tell you that one of them is called F_o, perhaps you can guess that this part binds oligomycin. When oligomycin binds to the enzyme, it can no longer make ATP from ADP plus phosphate. There are 2 very good pages on the web that explain how cells make ATP and where oligomycin comes in:
http://arc-gen1.life.uiuc.edu/Bioph354/lect10.html
http://www- isu.indstate.edu/thcme/mwking/oxphos.html

Next you ask for the structure of oligomycin. In fact there are several types of oligomycin called A, B and C. Oligomycin A is the one that we normally use. I scanned a picture of its structure for you from a paper, here it is:
In fact this is called 21-hydroxyl oligomycin A, you can probably work out why. It looks complex but is actually quite a simple structure-this type of compound is called a macrolide. It belongs to a large chemical family called polyketides. One final chemical word that we use to describe this structure is "spiroketal". These might all be useful words for you in a web search.

You ask for its biochemical pathway. I'm not sure what you meant by this- if you mean how does it work, the answer is above. If you mean how is it synthesised, this work was done in 1986 in Manchester, England. The researchers used simple carbon compounds (acetate, butyrate and propionate) labelled with carbon-13, fed these to the cells then extracted the oligomycin and looked at where the carbon-13 atoms were. In this way they could see that oligomycin is assembled piece by piece from smaller simple molecules containing carbon.

Finally, some "general" information. The "-mycin" part of oligomycin tells you that it is isolated from the bacterium Streptomyces, an organism that makes a lot of antibiotics. In fact oligomycin was first identified in 1953 from a species called Streptomyces diastatochromogenes, but it has since been found in lots of other streptomycetes.

I hope this has answered some of your queries. This story illustrates a common theme in science-often we use something a lot because it is useful in an experiment, even though we don't know very much about it! If you would like even more technical information (such as journal references), please let me know.

Neil Saunders