Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids.
Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids.
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DOI：
10.1002/anie.201902761
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发表时间：
2019-06
影响因子：
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通讯作者：
Yu Wang;Nadine Tappertzhofen;D. Méndez-Sánchez;Maria Bawn;Boyu Lyu;J. Ward;H. Hailes
中科院分区：
文献类型：
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作者：
Yu Wang;Nadine Tappertzhofen;D. Méndez-Sánchez;Maria Bawn;Boyu Lyu;J. Ward;H. Hailes
苄基异喹啉生物碱是一类重要的高等植物次生代谢产物，具有重要的生物活性。通过合成生物学方法生产BIA提供了比传统合成方法或从植物材料分离更高产的策略。然而，通过组合异源酶在微生物中重建BIA途径也可以通过级联反应获得BIA。最重要的是，非天然BIA可以通过这种人工途径产生。在目前的研究中，我们描述了使用酪氨酸酶和脱羧酶和联合收割机这些与转氨酶和去甲乌药碱合酶的有效合成的几个BIA，包括六个非天然生物碱，级联从L-酪氨酸和类似物。
The benzylisoquinoline alkaloids (BIAs) are an important group of secondary metabolites from higher plants and have been reported to show significant biological activities. The production of BIAs through synthetic biology approaches provides a higher-yielding strategy than traditional synthetic methods or isolation from plant material. However, the reconstruction of BIA pathways in microorganisms by combining heterologous enzymes can also give access to BIAs through cascade reactions. Most importantly, non-natural BIAs can be generated through such artificial pathways. In the current study, we describe the use of tyrosinases and decarboxylases and combine these with a transaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs, including six non-natural alkaloids, in cascades from l-tyrosine and analogues.