Elucidation of novel FPP-methyltransferase-terpene synthase gene clusters in Proteobacteria

变形菌中新型 FPP-甲基转移酶-萜烯合酶基因簇的阐明

• 批准号: 390586930
• 负责人: Professorin Dr. Birgit Piechulla
• 金额: --
• 依托单位: Abteilung Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/390586930?language=en
• 关键词: Elucidation; novel; FPP; methyltransferase; terpene

The classical biosynthesis of terpenoids is based on the usage of C10-GPP, C15-FPP or C20-GGPP as substrates, but a paradigm change has to be considered. A coupling of C-methylation and cyclization by the FPP methyltransferase with a non-classical terpene synthase represents an unprecedented reaction mechanism which was recently shown for the unique biosynthesis of sodorifen in Serratia plymuthica 4Rx13. It illustrates an alternative avenue to enlarge terpene diversity due to the utilization of a C16 substrate. Substrate specificity of the succeeding sodorifen synthase for the non-canonical, monocyclic pre-sodorifen pyrosphosphate implies the coevolution of both enzymes. Preliminary additional evidence of this coevolution is also found in Pseudomonas chlororaphis O6 which produces the novel bis-homoterpene chlororaphen. So far, C-methylations and cyclizations of prenyl pyrophosphates have been exclusively found in bacteria scrutinizing the origin of respective biosynthetic pathways. We hypothesize that in proteobacteria rather than in actinobacteria (e.g. Streptomyces species) C-methylation and cyclization of FPP was established for the biosynthesis of novel terpenoids. Here we will verify whether the biosynthesis the of C17 compound chlororaphen depends on two preceding methyltransferase reactions which are followed by a terpene synthase reaction. Moreover, we will test the hypothesis whether FPP methyltransferases were (exclusively/dominantly) manifested in proteobacteria during evolution.

萜类化合物的经典生物合成基于使用 C10-GPP、C15-FPP 或 C20-GGPP 作为底物，但必须考虑范式的改变。 FPP 甲基转移酶与非经典萜烯合酶的 C-甲基化和环化偶联代表了一种前所未有的反应机制，最近在普城沙雷氏菌 4Rx13 中独特的索多芬生物合成中得到了证实。它说明了由于使用 C16 底物而扩大萜烯多样性的替代途径。随后的索多芬合酶对非典型单环前索多芬焦磷酸的底物特异性意味着两种酶的共同进化。这种共同进化的初步额外证据也在绿针假单胞菌 O6 中发现，它产生新型双同三烯氯莱酚。到目前为止，异戊烯基焦磷酸的 C-甲基化和环化仅在细菌中发现，并仔细检查了各自生物合成途径的起源。我们假设在变形菌中而不是在放线菌（例如链霉菌属）中，FPP 的 C-甲基化和环化是为了生物合成新型萜类化合物而建立的。在这里，我们将验证C17化合物氯莱酚的生物合成是否依赖于前面的两个甲基转移酶反应以及随后的萜烯合酶反应。此外，我们将检验 FPP 甲基转移酶是否（唯一/主要）在进化过程中出现在变形菌中的假设。