Biosearch Italia SpA

In the course of a screening program for Nonomuraea sp. ATCC 39727 mutants with desirable characteristics, a clone showing a noteworthy activity in an overlay antimicrobial test was isolated.This mutant was able to directly produce demannosyl-A40926 with an abundance of ∼ 95% with respect to the other components of the antibiotic complex.The isolation of this strain allowed demannosyl-A40926 production by a single fermentation/purification process.

The biosynthesis of the antibiotic GE2270 in the producing microorganism Planobispora rosea was investigated by adding labelled amino acid precursors. Efficient incorporation of glycine and serine was observed, leading to specific enrichments of selected positions of the thiazole, oxazoline and pyridine rings. Furthermore, efficient enrichment of the C-, N- and O-methyl groups was detected. These results indicate that GE2270 is made through a biosynthetic route similar to that determined for other thiazolylpeptides. At the same time, the result point to an efficient route for the conversion of glycine into serine and methyl equivalents in Planobispora rosea.

The structure of a product, isolated during the synthesis of the semisynthetic glycopeptide MDL 63,246, was elucidated on the basis of spectroscopic methods and proved to be a novel glycopeptide containing a 3-oxazolin-5-one ring between positions 36 and 38. Subjected to acid hydrolysis this compound gave the corresponding pseudo aglycone and aglycone derivatives which maintained the original oxazolinone structure. Tested for antibacterial activity, these compounds showed a moderate activity against Gram-positive and inactive against Gram-negative bacteria.