Emerging concepts in the semisynthetic and mutasynthetic production of natural products

Natural products have greatly influenced the development of drugs to combat infectious diseases, cancer, and other disorders affecting human well-being. Only rarely, a natural product is used in an unmodified form for therapeutic purposes. More often, natural product derivatives are preferred due to improved activity or toxicity profiles. These compounds are usually produced using 'hybrid' processes that integrate organic synthesis and biosynthesis. Either a natural product is isolated from a biological source and then converted into the final drug by semisynthesis or a synthetically prepared precursor is introduced into the engineered biosynthesis of a living cell in a procedure called mutasynthesis. In this review, we will present recent developments in these two research areas, which take advantage of heterologous biosynthesis.