通过合成生物学平台阐明的鼠尾草酸生物合成。
Carnosic acid biosynthesis elucidated by a synthetic biology platform.
作者信息
Ignea Codruta, Athanasakoglou Anastasia, Ioannou Efstathia, Georgantea Panagiota, Trikka Fotini A, Loupassaki Sofia, Roussis Vassilios, Makris Antonios M, Kampranis Sotirios C
机构信息
Department of Biochemistry, School of Medicine, University of Crete, Heraklion 71003, Greece;
Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Athens 15771, Greece;
出版信息
Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):3681-6. doi: 10.1073/pnas.1523787113. Epub 2016 Mar 14.
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.
合成生物学方法致力于在特定的微生物“底盘”中重建特定植物天然产物生物合成途径，从而获得了重要的工业化合物（如青蒿素、白藜芦醇、香草醛）。然而，此类生产系统在促进植物生物合成途径阐释方面的潜力尚未得到充分探索。在此，我们报告了一种模块化萜类化合物生产平台在表征导致强效抗氧化剂迷迭香酸及相关二萜类化合物生物合成途径中的应用，该途径存在于多育鼠尾草和迷迭香中。我们鉴定出了四种细胞色素P450酶（CYP76AH24、CYP71BE52、CYP76AK6和CYP76AK8），它们的联合活性解释了导致这些植物中主要二萜类化合物生物合成的所有氧化事件。这种方法将酵母开发成了一种高效工具，可利用通过转录组学或基因组学研究越来越容易获得的大量测序数据集的生物技术潜力。
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