Werner R G, Demain A L
J Antibiot (Tokyo). 1981 May;34(5):551-4. doi: 10.7164/antibiotics.34.551.
Tryptophan in a concentration of 0.4 microgram/ml increased the production of indolmycin by 37%. The lipophilic character of indolmycin was reduced via directed biosynthesis by substituting the aromatic ring system with a methoxy or hydroxy group in the 5-position of the antibiotic. This substitution was achieved by the addition of the corresponding tryptophan and indole precursors to a growing culture of Streptomyces griseus ATCC 12648. The more hydrophilic indolmycin derivatives displayed a moderate increase in antimicrobial activity as compared to indolmycin, but did not markedly change the Gram-positive/Gram-negative ratio of activity. Thin-layer chromatography and mass spectrometry showed that additives substituted in the 6-position were not incorporated into the molecule. Antibiotic titer was reduced by addition of the modified precursors, especially in the case of the precursors substituted in the 6-position.
浓度为0.4微克/毫升的色氨酸使吲哚霉素的产量提高了37%。通过在抗生素的5位用甲氧基或羟基取代芳香环系统，经定向生物合成降低了吲哚霉素的亲脂性。这种取代是通过向灰色链霉菌ATCC 12648的生长培养物中添加相应的色氨酸和吲哚前体来实现的。与吲哚霉素相比，亲水性更强的吲哚霉素衍生物的抗菌活性有适度提高，但革兰氏阳性/革兰氏阴性活性比没有明显变化。薄层色谱法和质谱分析表明，在6位取代的添加剂没有掺入分子中。添加修饰前体降低了抗生素效价，尤其是在6位取代的前体情况下。
