Use of a Heterologous Gene for Molecular Breeding of Actinomycetes Producing Structurally Related Antibiotics: Self-defense Genes of Producers of Fortimicin-A (Astromicin)-group Antibiotics

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Self-defense genes of fortimicin (Fm)-group antibiotic producers varied between genera, and can be classified into two groups regarding to their resistance profiles and DNA homologies. DNA sequence analyses revealed that the resistance genes of the Streptomyces and Saccharopolyspora producers encode methyltransferases capable of modifying 16S rRNA as same as kamB of a nebramycin producer, Streptomyces tenebrarius, and that those of the Micromonospora and Dactylosporangium producers encode another type of 16S rRNA methyltransferases similar to grmA of a gentamicin producer, Micromonospora purpurea. A Fm-A producer, Micromonospora olivasterospora, transformed by the Fm-resistance gene (fmrT) of Streptomyces tenjimariensis showed significant increase of the resistance level to Fm-A. This result indicated that heterologous genes from producers of the structurally related antibiotics are useful as DNA sources for the molecular breeding of antibiotic producers.