There are two main obstacles: actually making a new molecule with a PKS, and getting it to be active enough to make useful and financially viable quantities of

There are two main obstacles: actually making a new molecule with a PKS, and getting it to be active enough to make useful and financially viable quantities of a product. Both are challenging. A substantial fraction of the currently used pharmaceuticals, especially big complex antibiotics are already made commercially at scale with PKSs- but mostly in cases where they are just using the natural organism with its natural PKS. They are challenging to engineer, e.g. "get parts to work together" in an unnatural order but that has been getting better over time, with lots of recent breakthroughs, and a bunch of new molecules being made, but the production quantities do tend to be low. There is no fundamental reason why PKSs have to be slow, or make small quantities of things, there are a few good examples of both natural products and engineered PKSs that make things in really high concentrations. So this is presumably something that can be improved over time, but is definitely the biggest weakness, which limits commercial viability right now to high value things like drugs.