74 IdiotrophおよびCeruleninを利用するTylosinおよび関連化合物の生合成研究

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We have obtained a mutant strain No. 261 by the treatment of the tylosin (1) producing strain, Streptomyces fradiae KA-427, with nitrosoguanidine. The structures of protylonolide (3) and mycarosyl protylonolide (4) isolated from the culture broth of the mutant were elucidated by mass and nmr spectrometry and X-ray crystallography. The absolute configuration of 1 was deduced from the evidence that 3 is bioconverted to 1 and spectral identity of 1, 3 and leucomycin A_3 in which the absolute configuration was already established. Cofermentation and bioconversion studies indicated that mutant No. 261 is an idiotroph of mycaminose. Hybrid biosynthesis of tylosin-related compound was attempted using an antibiotic producer and cerulenin, an inhibitor of polyketide biosynthesis. The feeding of 3 to the fermentation broth of Streptomyces sp. AM-4900 producing picromycin, a 14-membered macrolide antibiotic, gave a product designated as 5-O-desosaminyl protylonolide (9) (=M-4365 G_1, 6). Consequently, it was found that the absolute configuration of M-4365 G_<1-3> (6, 7, 8) are identical with that of 1. Furthermore, in order to clarify the biosynthetic pathway after the lactone ring formation of 1, we attempted the syntheses of many tylosin-related compounds and examined the ability for the bioconversion of these compounds to 1 by Sm. fradiae in the presence of cerulenin. As a result, the preferred pathway from 3 to 1 are as follows: 1) addition of mycaminose to C_5-OH of 3; 2) oxidation of C_<20>-methyl to aldehyde and C_<23>-methyl to alcohol in undetermined order; 3) addition of mycinose to C_<23>-OH; 4) addition of mycarose to C_4'-OH. The biosynthetic relation of 1 and relomycin (2) is also discussed.
天然有機化合物討論会の論文
1980-09-10

74 IdiotrophおよびCeruleninを利用するTylosinおよび関連化合物の生合成研究

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