Biosynthesis of the isoprenoid moieties of furanonaphthoquinone I and endophenazine A in Streptomyces cinnamonensis DSM 1042
Biosynthesis of the isoprenoid moieties of furanonaphthoquinone I and endophenazine A in Streptomyces cinnamonensis DSM 1042
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DOI：
10.1021/jo0703404
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发表时间：
2007-05-25
影响因子：
3.6
通讯作者：
Heide, Lutz
中科院分区：
文献类型：
--
作者：
Bringmann, Gerhard;Haagen, Yvonne;Heide, Lutz
肉桂链霉菌DSM 1042产生聚酮-类异戊二烯化合物呋喃萘醌I（FNQ I）和异戊二烯化吩嗪，主要是内吩嗪A。然而，最近鉴定的这些化合物的生物合成基因簇仅包含甲羟戊酸途径酶的单个基因，即推定的甲羟戊酸激酶基因。这与迄今为止检测的所有链霉菌菌株形成强烈对比，其中编码甲羟戊酸途径酶的所有六个基因聚集在6.8kb的单个操纵子中，因此提出了关于FNQ I和内吩嗪A的类异戊二烯部分的生物合成来源的问题。在这项研究中，我们研究了[C-13（2）]乙酸酯和[2-C-13]甘油掺入FNQ I和endophenazine A。结果明确证明，两种化合物的类异戊二烯结构单元主要通过甲羟戊酸途径形成（约80%），但MEP途径（约20%）也有助于这些分子的生物合成。在放线菌中，这是第一个实验证明的例子，利用两种生物合成途径形成一个单一的次级代谢产物。[2-C-13]甘油的掺入模式与“反向”异戊二烯基转移一致，即，与从GPP的C-3到FNQ I的聚酮核的C-C键的形成一致。
Streptomyces cinnamonensis DSM 1042 produces the polyketide-isoprenoid compound furanonaphthoquinone I (FNQ I) and isoprenylated phenazines, predominantly endophenazine A. However, the recently identified biosynthetic gene cluster for these compounds only contains a single gene for a mevalonate pathway enzyme, that is, a putative mevalonate kinase gene. This is in strong contrast to all Streptomyces strains examined so far, where all six genes encoding the mevalonate pathway enzymes are clustered in a single operon of 6.8 kb and, thus, raised the question about the biosynthetic origin of the isoprenoid moieties of FNQ I and endophenazine A. In this study, we investigated the incorporation of [C-13(2)]acetate and [2-C-13]glycerol into FNQ I and endophenazine A. The results unequivocally prove that the isoprenoid building blocks of both compounds are predominantly formed via the mevalonate pathway (approximately 80%) but that the MEP pathway (approximately 20%) contributes to the biosynthesis of these molecules, too. In actinomycetes, this is the first experimentally proven example of the utilization of both biosynthetic routes for the formation of one single secondary metabolite. The incorporation pattern of [2-C-13]glycerol was consistent with a "reverse" prenyl transfer, that is, with the formation of a C-C bond from C-3 of GPP to the polyketide nucleus of FNQ I.