The analysis of the biosynthetic gene clusters of natural products unravels that natural products are not necessarily built according to their biosynthetic plan. This might be due to an evolutionary change of the structure of polyketides. Being able to predict the structure of natural products by looking at their biosynthetic enzymes, we can start synthesizing natural products as if their fully obey their biosynthetic plan. This approach might shed light on the origin of their mode of action and help to discover new biologically active compounds. This concept will exemplified with the soraphens and tedanolides. Besides looking at the biological activity, the lecture will cover the pivotal transformation leading to these natural products.