The Shared Steps of Lincomycine and Pyrrolo-benzodiazepine Biosynthetic Pathways.

Lincomycin and its semi-synthetic derivate clindamycin are therapeutically used antibiotics inhibiting protein synthesis in sensitive bacteria. Their structure is composed of an amino-sugar and an amino-acid moiety, which are linked with an amide bond. Some time ago the sequence of lincomycin-production gene cluster was established and functions of the most proteins coded from gene cluster were proposed on the basis of a comparison with known proteins and gene-inactivations. For a long time it was clear that the amino-acid moiety of linkomycin (propylproline) is related to a dihydropyrrol moiety of pyrrolo[1,4]benzodiazepine (PBD). Both of these moieties are derived from L-tyrosine and they undergo the same biosynthetic pathway at first. But other biosynthetic steps divide. It is believed that a transfer of genes from the PBD-production gene cluster to the lincomycin-production gene cluster could modify the structure of propylproline and improve traits of lincomycin e.g. increase antimalaric effects. The most effective antibiotics are alkyl derivatives, their chemical synthesis is very complicated, but they could be prepared via genetic engineering as so-called hybrid antibiotics