Carnosic acid biosynthesis elucidated by a synthetic biology platform
Carnosic acid biosynthesis elucidated by a synthetic biology platform
复制标题
DOI：
10.1073/pnas.1523787113
复制
发表时间：
2016-03-29
影响因子：
11.1
通讯作者：
Kampranis, Sotirios C.
中科院分区：
文献类型：
--
作者：
Ignea, Codruta;Athanasakoglou, Anastasia;Kampranis, Sotirios C.
在专用微生物“底盘”中实现特定植物天然产物生物合成途径重建的合成生物学方法提供了获得重要工业化合物(例如青蒿素、白藜芦醇、香草醛)的途径。然而，这种生产系统在促进阐明植物生物合成途径方面的潜力还没有得到充分的探索。在这里，我们报道了一个模块化的萜烯生产平台在鉴定鼠尾草和迷迭香中产生有效抗氧化剂鼠尾草酸和相关二萜的生物合成途径中的应用。已鉴定出四种细胞色素P450酶(CYP76AH24、CYP71BE52、CYP76AK6和CYP76AK8)，它们的结合活性解释了导致这些植物产生的主要二萜类化合物生物合成的所有氧化事件。这种方法将酵母发展为一种有效的工具，可以利用大量测序数据集的生物技术潜力，这些数据集越来越多地通过转录组或基因组研究变得可用。
Synthetic biology approaches achieving the reconstruction of specific plant natural product biosynthetic pathways in dedicated microbial "chassis" have provided access to important industrial compounds (e.g., artemisinin, resveratrol, vanillin). However, the potential of such production systems to facilitate elucidation of plant biosynthetic pathways has been underexplored. Here we report on the application of a modular terpene production platform in the characterization of the biosynthetic pathway leading to the potent antioxidant carnosic acid and related diterpenes in Salvia pomifera and Rosmarinus officinalis. Four cytochrome P450 enzymes are identified (CYP76AH24, CYP71BE52, CYP76AK6, and CYP76AK8), the combined activities of which account for all of the oxidation events leading to the biosynthesis of the major diterpenes produced in these plants. This approach develops yeast as an efficient tool to harness the biotechnological potential of the numerous sequencing datasets that are increasingly becoming available through transcriptomic or genomic studies.