Elucidation of structure of novel macrolide antibiotics produced by mutant strains of Streptomyces fradiae.
نویسندگان
چکیده
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 of these mutant strains in fermentation, cofermentation, in vitro enzymatic and in vivo bioconversion studies, it was proposed that tylosin is assembled via a preferred series of biosynthetic steps'-'). This proposal is further supported by in vitro studies recently reported by OMURA and coworkers'). Since the substrate specificities of certain enzymes involved in tylosin biosynthesis are not particularly stringent, blocked biosynthetic steps involving those enzymes were readily bypassed in particular mutant strains of S. fradiae'-','). Consequently, some of the mutants produced biosynthetic intermediates to tylosin in high yield while others produced shunt metabolites, many of which possessed antimicrobial activity"). Since many of these biosynthetic intermediates and shunt metabolites had not been previously reported, they were isolated and identified by physicochemical methods. After our work had been completed, a communication from another group was published describing a series of compounds which had been obtained from an independently-derived set of mutants which were blocked in various steps of tylosin biosynthesis". In this paper, we report our work on the isolation and elucidation of structure of the 16-Iembered macrolides which have been obtained from the biosynthetically-blocked mutants of S. fi•adiae previously described').
منابع مشابه
Direct fermentative production of acyltylosins by genetically-engineered strains of Streptomyces fradiae.
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متن کاملNovel fermentation products from Streptomyces fradiae: X-ray crystal structure of 5-O-mycarosyltylactone and proof of the absolute configuration of tylosin.
5-O-Mycarosyltylactone has been isolated as a predominant factor from fermentation broths of a Streptomyces fradiae mutant. The relative configurations of mycarose and tylactone (protylonolide) have been determined by X-ray crystal structure analysis. Hydrolysis of 5-O-mycarosyltylactone yielded (-)-tylactone and L-(-)-mycarose. Taken together, these two experiments establish the absolute confi...
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عنوان ژورنال:
- The Journal of antibiotics
دوره 36 4 شماره
صفحات -
تاریخ انتشار 1983