Biosyntheses of Novel Emycins from the Mutant Strain Streptomyces celluiosae ssp. griseoincarnatus 1114-2

摘要

The development of concepts for the search for structurally novel natural products which may eventually serve as lead structures for pharmaceutical or other indications is a permanent challenge, increased by resistance problems. This challenge may befaced in particular in academic research institutions, since sufficient test assays established on the industrial side are waiting for use. Parallel to the concept of creating novel natural products through targeted genetic modifications of poly Reticle-producing streptomycetes. we also use the often faster approach of arbitrarily genetically modifying selected strepto-mycetes. In this context we are particularly interested in those polyketide producers whose product spectra are obviously influenced byoxidoreductases. A good example is Sirepionines cel-lulosae ssp. griseoincarnutus(FH-S 1 1 14), an angucyclinone producer yielding elmycin D (1) as the major product, the known antibiotics ochromycinone (2) and deoxyrabelomycin (3) as minor products, and. among others, ernycin A (4) as trace products. From this product spectrum one can assume a biosynthetic relationship between these four metabolites resulting from oxidoreductase activities. Oxygenases are especially able to markedly modify a primary biosynthetic molecular backbone, as known from the biosynthesis of the polyether antibiotic monensin or prostaglandins. Thus a mutation of a strain showing intense oxidoreductase activities may result in a whole spectrum of novel products.