Shared features and analysis of lincosamide and anthramycin antibiotic gene clusters

Jelínková, Markéta

Lincomycin, produced by Streptomyces lincolnensis, is important, clinically used antibiotic. Its gene cluster consists of twenty-seven putative open reading frames with biosynthetic or regulatory functions and three resistance genes. Comparison of the chemical structure of the lincomycin and celesticetin indicates, that in the biosynthesis of celesticetin the whole propylproline branch is absent and proline is substrate of the penultimate step of biosynthesis, the condensation reaction. Second part of biosynthetic pathway including conversion of L-tyrosine to L-proline should be involved in the biosynthesis of functionally different anthramycin antibiotics. Thus it appears, that genetic information on lincomycin and anthramycin biosynthesis must also share common elements (genes), both biosynthetic and regulatory. The organization of transcription units was found. The analysis of the lincomycin biosynthetic gene transcripts in various cultivation stages revealed the genes with putative regulatory functions which are transcribed sooner. A set of probes based on the sequence of lincomycin biosynthetic cluster was used to search for analogous genes in celesticetin producer Streptomyces caelestis and three producers of anthramycin antibiotics: Streptomyces refuineus, Streptomyces albus and Streptosporangium sibiricum. Hybridization experiments proved presence of several analogues of genes coding for sugar moiety biosynthesis in S. caelestis and analogues of some genes coding for anthramycin antibiotics in different anthramycin producers. A rough restriction map of a part of celesticetin gene cluster presumably responsible for sugar moiety biosynthesis shows the gene arrangement to be very similar to that of lincomycin biosynthetic cluster.

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