While natural products often exhibit highly potent and
selective bioactivity, they did not undergo evolutionary
selection to serve as human therapeutics and, thus, have not
been fine-tuned to possess the potency, selectivity, and
pharmacokinetic properties desired in a clinically useful drug.
Optimization frequently entails modification, removal, or
introduction of functional groups and stereocenters or more
drastic remodeling of the basic scaffold to improve physicochemical
and pharmacokinetic properties. The structural
diversity accessible by combinatorial biosynthetic methods
is limited by the available biosynthetic pathways of the host
organism; however, the power of synthetic chemistry can
be harnessed to access a greater extent of possible modifications
and structural diversity than biosynthetic methods alone.