Biosynthesis of A6\u277-anhydroerythromycin via enoyl reductase inhibition by isonicotinic hydrazide (INH)

Isonicotinic hydrazide (INH) was added to a fermentation of mutant of Saccharopolyspora erythraea ATCC 11912 to inhibit the activity of 2,4,6,8-tetramethyI-7,9-dihydroxy-2-en-5-on-undecyl-ACP enoyl reductase, an enzyme which catalyses enoyl reduction process of an intermediate in the erythronolide biosynthesis, and produce A"3-anhydroerythromycin derivative. The. optimum INH additional concentration of above 0.1% was able to inhibit the enzyme activity, and produce A6â¢7-anhydroerythromycin derivative as shown by FT-infrared spectrophotometric analysis of the product after its purification using thin layer chromatography. Keywords: Isonicotinic hydrazide (INH) enoyl reductase â d7-anhydroerythromycin â mutant Saccharopolyspor

Structural elucidation of A6\u277-anhydroerythromycin D using H-NMR-spectrometer

1-1-NMR-spectrometric analysis was carried out to samples I and 2 which were isolated respectively from Saccharopolyspora erythraea ATCC 11912 with and without additional isonicotinic hydrzide (INH). The sample I was confirmed as erythromycin D due to the proton appearance of 12-H at 32.3175 (dq) of the macrolactone, and the absence of 3"-niethoxy proton at 3.31 (s) of its neutral sugar. The sample 2 was confirmed as 46\u277-anhydroerythromycin D due to the presence of 7-H(-C=C-) at 35.343 (dq) instead of the methylene proton at C,and the presence of proton 12-Hat 82.318 (dq) of the macrolactone