Metabolic regulation in tylosin-producing Streptomyces fradiae: phosphate control of tylosin biosynthesis.

Phenotypic changes associated with loss of expression of tylosin biosynthesis and resistance genes in Streptomyces fradiae.

Two mutants of the tylosin-producing Streptomyces fradiae defective in the biosynthesis of the macrolide antibiotic tylosin were isolated from colonies derived from regenerated protoplasts. Both strains were unable to carry out any of at least seven tylosin biosynthetic steps and were sensitive to tylosin. One strain, JS82, was also more sensitive to chloramphenicol (Cm), mitomycin C (Mc), hygr...

The tylosin biosynthetic cluster from Streptomyces fradiae: genetic organization of the left region.

The genetic organization of the left edge (tyIEDHFJ region) of the tylosin biosynthetic gene cluster from Streptomyces fradiae has been determined. Sequence analysis of a 12.9 kb region has revealed the presence of 11 ORFs, 10 of them belonging to the biosynthetic cluster. The putative functions of the proteins encoded by these genes are as follows: peptidase (ORF1, ddcA), tylosin resistance de...

Elucidation of structure of novel macrolide antibiotics produced by mutant strains of Streptomyces fradiae.

Tylosin is a 16-membered macrolide antibiotic which is produced commercially by strains of Streptomyces fradiae'•1' and is composed of a substituted lactone (tylonolide), an amino sugar (mycaminose) and two neutral sugars (mycinose, mycarose)'). Recently, a series of mutants of S. fi•adiae which are blocked in specific steps in the biosynthesis of tylosin has been described". From an analysis o...

Production of mycarosyl protylonolide by a mycaminose idiotroph from the tylosin-producing strain Streptomyces fradiae KA-427.

The mycarose-biosynthetic genes of Streptomyces fradiae, producer of tylosin.

The tylCK region of the Streptomyces fradiae genome was sequenced, revealing an incomplete set of five tylC genes encoding all-but-one of the enzymes involved in the biosynthesis of mycarose. The latter is a 6-deoxyhexose sugar required during production of the macrolide antibiotic, tylosin. The missing mycarose-biosynthetic gene, tylCVI, was found about 50 kb distant from its functional partne...