Biosynthetic Studies of terpenoids produced by actinomycetes

长期以来，人们一直认为异戊烯基二磷酸（IPP），萜类化合物的起始单元，是通过经典的甲羟戊酸途径产生的。Rohmer最近发现的新的非甲羟戊酸途径提出了一个问题，链霉菌利用这两种途径中的哪一种？为了解决这个有趣的问题，我们已经研究了由链霉菌产生的萜类化合物，如萘，longestin，carquinostatin和新生霉素的生物合成。此外，还利用^ C-和^2 H-标记的前体研究了由游动放线菌产生的萜类化合物BE-40644的生物合成<13>，结果发现，一些链霉菌（longestin、carquinostatin和新生霉素产生菌）仅具有非甲羟戊酸途径，而另一些链霉菌（萘啶、呋喃喹辛、萘放射霉素和BE-40644产生菌）可以利用这两种途径。属于后一组的链霉菌在早期生长阶段使用非甲羟戊酸途径，然后逐渐将该途径转换为甲羟戊酸途径。我们从产萘素的金黄色链霉菌（Streptomyces aureouvifer）中纯化了HMG Co-A还原酶，并根据所获得的氨基酸序列制备了DNA探针。Southern杂交分析表明，甲羟戊酸途径的存在和链霉菌生物体的分类位置之间似乎没有关系。

It has long been believed that isopentenyl diphosphate (IPP), a starting unit of terpenoid Compound, is produced by the classical mevalonate pathway. Recent finding of the new non- mevalonate pathway by Rohmer raised a question which of the two pathways do Streptomycetes utilize? In order to address this interesting question, we have studied the biosynthesis of terpenoidal compounds produced by Streptomyces such as naphterpin, longestin, carquinostatin and novobiocin. In addition, the biosynthesis of a terpenoid BE-40644 produced by Actionoplanes was also studied byusing ^<13>C- and ^2H-labeled precursors.AS a result, it has turned out that several Streptomycetes (longestin, carquinostatin and novobiocin producers) possess only the non-mevalonate pathway, while some others (naphterpin, furaquinocin, napyradiomycin and BE-40644producers) can utilize both the pathways. Streptomycetes belonging to the latter group use the non-mevalonate pathway at earlier growth stage and then gradually the pathway is switched to the mevalonate pathway. Such switching of the metabolic pathways depending on the growth has never been reported.Then we purified HMG Co-A reductase from Streptomyces aureouvifer, a producer of naphterpin, and prepared a DNA probe based on the obtained amino acid sequence. Southern hybridization analysis showed that there seems to be no relationship between the presence of the mevalonate pathway and the taxonomical position of Streptomyces organisms.