Pekka Patrikainen

University of Turku
Supervisor: Jarmo Niemi
Funding: ISB
Date: 2012-01-01

Molecular basis for the diversity of angucycline antibiotics

Angucyclines are a large group of aromatic type II polyketides, which have been associated to various biological activities. These compounds are ubiquitous in nature and are mainly produced by Streptomyces bacteria. The vast diversity of angucyclines produced in nature is largely due to the different oxygenases, reductases and glycosyltransferases that modify the first stable angucycline intermediate UWM6 into different products.

In this study I will investigate angucycline modification enzymes from five different biosynthetic pathways that produce different angucycline metabolites: gaudimycins, jadomycins, landomycins and urdamycins. The biosynthetic genes responsible for the production of these compounds are homologous and distributed in a conserved order in all five pathways. Enzymes under study are FAD-dependent oxygenases (OXY) and short-chain alcohol dehydrogenases/reductases (SDR).

The aim of this study is to determine how homologous enzymes are able to catalyze the formation of structurally different products. I have expressed and purified all the chosen modification enzymes and measured their activities, using different methods, alone and in combination with other enzymes to see if new products are formed. Next goal is to interchange regions between interesting enzymes in order to find out which parts are responsible for their different functions. One of the goals is also to determine the 3D structures of the enzymes under study to see what differences in enzyme structure are responsible for the different activities.