The Discovery of Imine Reductases and their Utilisation for the Synthesis of Tetrahydroisoquinolines.
The Discovery of Imine Reductases and their Utilisation for the Synthesis of Tetrahydroisoquinolines.
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DOI：
10.1002/cctc.202201126
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发表时间：
2023-02-08
期刊：
影响因子：
4.5
通讯作者：
Ward, John M.
中科院分区：
文献类型：
--
作者：
Cardenas-Fernandez, Max;Roddan, Rebecca;Carter, Eve M.;Hailes, Helen C.;Ward, John M.
关键词：
亚胺还原酶(IRED)是一种依赖于NADPH的酶，在合成伯手性胺、仲手性胺和叔手性胺方面具有巨大的生物催化潜力。它们的应用包括环亚胺的还原和前手性酮的还原胺化。在本研究中，通过基因组挖掘发现了29个新的IRED。亚胺还原酶在pH为 7和9的条件下，在NADPH或NADH的存在下都有活性；一些IRD在这两种pH下都表现出很好的活性，并能够接受这两种辅因子。天冬氨酸和谷氨酸位于187个关键残基的IRED对NADH有偏好。IRED还与一系列二氢异喹啉进行筛选，以合成四氢异喹啉(THIQ)，这是一种具有广泛治疗性质的生物活性生物碱。当与葡萄糖-6-磷酸脱氢酶结合用于NADPH辅因子循环时，所选的IRED显示出高的立体选择性以及高的THIQ产率(>；90 %)。从9种微生物中筛选出29个新的亚胺还原酶(IRED)，并在不同条件下对其活性进行了模拟底物筛选。红外发光二极管被成功地用于合成四氢异喹啉(THIQs)，这是一种具有广泛治疗性质的生物活性生物碱。
Imine reductases (IREDs) are NADPH‐dependent enzymes with significant biocatalytic potential for the synthesis of primary, secondary, and tertiary chiral amines. Their applications include the reduction of cyclic imines and the reductive amination of prochiral ketones. In this study, twenty‐nine novel IREDs were revealed through genome mining. Imine reductase activities were screened at pH 7 and 9 and in presence of either NADPH or NADH; some IREDs showed good activities at both pHs and were able to accept both cofactors. IREDs with Asn and Glu at the key 187 residue showed preference for NADH. IREDs were also screened against a series of dihydroisoquinolines to synthesise tetrahydroisoquinolines (THIQs), bioactive alkaloids with a wide range of therapeutic properties. Selected IREDs showed high stereoselectivity, as well high THIQ yields (>90 %) when coupled to a glucose‐6‐phosphate dehydrogenase for NADPH cofactor recycling. Twenty‐nine novel Imine reductases (IREDs) were mined from 9 microorganisms, and their activity screened against model substrates and at different conditions. IREDs were successfully used for the synthesis of tetrahydroisoquinolines (THIQs), bioactive alkaloids with a wide range of therapeutic properties.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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