The assembly-line polyketide synthases of actinomycetes produce bioactive natural products with exquisite stereospecificity,and this plays a major role in determining their biological activity.Recent work,both in vivo and in vitro,will be described that sheds light on the molecular basis for this stereospecificity,both in the initial construction of the polyketide chain,and in the subsequent post-PKS tailoring events required to produce the fully-processed antibiotic.