Biosynthetic Studies of terpenoids produced by actinomycetes

二磷酸异戊烯酯（IPP）是萜类化合物的起始单位，一直被认为是由经典的甲羟戊酸途径产生的。侯麦最近发现的新的非甲羟戊酸途径提出了一个问题，即链霉菌利用的是两种途径中的哪一种？为了解决这一有趣的问题，我们研究了链霉菌产生的萜类化合物的生物合成，如萘酚素、长estin、carquinostatin和novobiocin。此外，还利用^<13 bb0 C-和^ 2h标记的前体研究了Actionoplanes生产的萜类BE-40644的生物合成。结果表明，一些链霉菌（longestin、carquinostatin和novobiocin产生者）仅具有非甲羟戊酸途径，而另一些链霉菌（萘酚、呋喃醌、napyradiomycin和be -40644产生者）可以同时利用这两种途径。后一类链霉菌在生长早期使用非甲羟戊酸途径，然后逐渐切换到甲羟戊酸途径。这种依赖于生长的代谢途径的转换从未被报道过。然后我们从产石脑油素的金黄色链霉菌（Streptomyces aurevifer）中纯化了HMG Co-A还原酶，并根据得到的氨基酸序列制备了DNA探针。南方杂交分析表明，甲羟戊酸途径的存在与链霉菌的分类地位似乎没有关系。

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.