Dr. Alan Scott
Dissection of Iterative Polyketide Synthases
Squalestatin Tetraketide Synthase (SQTKS) and 3-methylorcinaldehyde synthase (MOS) are iterative polyketide synthases from the filamentous fungi Phoma sp. And Acremonium strictum respectively. They are large enzymes with six catalytic domains and an acyl carrier protein which holds the growing chain. Some of the catalytic domains are selectively switched on or off during chain elongation to control the extent of modification of each ketide unit that is added. Thus the polyketide synthases are said to be programmed.
The large size of the enzymes (almost 300 kDa) makes it difficult to produce sufficient quantities of active recombinant protein for kinetic and structural studies. Therefore work has begun to dissect the corresponding genes into segments for the production of individual domains in a variety of expression systems. Soluble domains are being taken forward for structural studies by X-ray crystallography.