6533b82bfe1ef96bd128e10d

RESEARCH PRODUCT

Hybrid compounds generated by the introduction of a nogalamycin-producing plasmid into Streptomyces argillaceus

subject

description

The combination of genetic material from different antibiotic-producing organisms is a versatile and ever-expanding approach for the production of novel, hybrid compounds possessing bioactivity. The introduction of a plasmid (pSY21b) derived from Streptomyces nogalater and encoding PKS for nogalamycin production into the host strain S. argillaceus A43 led to the production of three new compounds in addition to the normally produced mithramycin. The new compounds are hybrids in the sense that they share features associated with the genes of both the host and the introduced plasmid. The structural elucidation of the novel compounds relied primarily on NMR spectroscopy, which revealed the three hybrids to be glycosides with the same aglycone common to all. Determination of the relative stereochemistry within the aglycone unit was confirmed by single-crystal X-ray analysis of the aglycone, which also revealed the tautomeric equilibrium to be in a very different position in comparison to that in the solution state. The glycosylation profile was clearly determined by the host, as the typical mithramycin sugars, D-oliose, D-olivose, and D-mycarose, were all expressed. Notable for the mutant was the high titre of the shunt products, 60% of the metabolic output, together with a lack of structural diversity of the hybrid aglycone present in the products, two features which are not normally observed.