Discussion

Biology is currently undergoing a major transition: the availability of complete genome sequences and our ability to manipulate/re-design genomes on a large scale enable the construction of completely new life forms (“synthetic biology”). The biosynthesis gene clusters of natural products are naturally modular, thus an ideal system to apply synthetic biology and engineer new and diverse bioactive molecules. We explore these possibilities in Streptomyces by studying the enzymatic building blocks and regulatory circuitry, and apply computational modelling of bacterial metabolism to identify suitable overproduction hosts and pinpoint biosynthetic bottlenecks that will be targeted for further cellular engineering.