Mayer M, Thiericke R
Institut für Organische Chemie, Universität Göttingen, Germany.
J Antibiot (Tokyo). 1993 Sep;46(9):1372-80. doi: 10.7164/antibiotics.46.1372.
In the late biosynthesis of the decarestrictines, inhibitors of the de novo formation of cholesterol isolated from the culture broth of Penicillium simplicissimum (FH-A 6090), a common pentaketide precursor undergoes post-polyketide modifications leading to the different members of the decarestrictine family. Besides subsequent enzymatically catalyzed reactions an unexpected non-enzymatic conversion was found to be the key step in the biosynthetic sequence. Under acidic conditions during fermentation the decarestrictines A1 and A2 (3 and 4) are converted into the main product decarestrictine D (2) and the new decarestrictines N (5) and O (6), whose physico-chemical data are reported. Mechanistic aspects of the non-enzymatic reaction as well as a more detailed picture of the biosynthetic relationships of the decarestrictine family are described. By the application of pH-static fermentations these results were successfully used to manipulate the secondary metabolite pattern of strain FH-A 6090 directing the fermentation process to produce desired members of the decarestrictine family.
在去甲甾醇菌素的后期生物合成过程中，从简单青霉（FH-A 6090）培养液中分离得到的胆固醇从头合成抑制剂，一种常见的五酮前体经过聚酮后修饰，生成了去甲甾醇菌素家族的不同成员。除了后续的酶催化反应外，还发现了一个意想不到的非酶促转化是生物合成序列中的关键步骤。在发酵过程中的酸性条件下，去甲甾醇菌素A1和A2（3和4）转化为主要产物去甲甾醇菌素D（2）以及新的去甲甾醇菌素N（5）和O（6），本文报道了它们的物理化学数据。描述了非酶促反应的机理方面以及去甲甾醇菌素家族生物合成关系的更详细情况。通过应用pH静态发酵，这些结果成功地用于操纵菌株FH-A 6090的次生代谢产物模式，引导发酵过程产生所需的去甲甾醇菌素家族成员。
