Engineering a Biometallic Whole Cell Catalyst for Enantioselective Deracemization Reactions
Engineering a Biometallic Whole Cell Catalyst for Enantioselective Deracemization Reactions
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DOI：
10.1021/cs200400t
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发表时间：
2011-11-01
期刊：
影响因子：
12.9
通讯作者：
Lloyd, Jonathan R.
中科院分区：
文献类型：
--
作者：
Foulkes, Joanne M.;Malone, Kirk J.;Lloyd, Jonathan R.
微生物细胞合成高活性纳米级功能材料的能力为开发下一代多功能工业生物催化剂的新型合成生物学工具提供了基础。在这里，我们证明了大肠杆菌，基因工程过量生产重组单胺氧化酶对手性胺具有高对映体选择性的有氧文化，可以增强与纳米级Pd（0）沉淀通过生物还原反应。其结果是一种新型的双环戊二烯基催化剂，用于外消旋胺的去外消旋化。该去外消旋化过程通常通过分别使用单独的对映体特异性生物催化剂和金属催化剂的离散顺序氧化/还原步骤来实现。这里，使用E.将携带克隆的单胺氧化酶基因和纳米级生物还原的Pd（0）颗粒的大肠杆菌培养物成功地用于外消旋1-甲基四氢异喹啉（MTQ）的转化，通过中间体1-甲基-3，4-二氢异喹啉转化为（R）-MTQ，对映体过量高达96%。在五轮氧化和还原之后没有催化剂活性的损失，并且重要的是，钯损失到反应上清液中最少。这是首次展示用于“单锅”多步反应的全细胞生物催化剂混合物，为广泛的集成工艺开辟了道路，提供了可扩展和高度灵活的平台技术。
The ability of microbial cells to synthesize highly reactive nanoscale functional materials provides the basis for a novel synthetic biology tool for developing the next generation of multifunctional industrial biocatalysts. Here, we demonstrate that aerobic cultures of Escherichia coli, genetically engineered to overproduce a recombinant monoamine oxidase possessing high enantioselectivity against chiral amines, can be augmented with nanoscale Pd(0) precipitated via bioreduction reactions. The result is a novel biometallic catalyst for the deracemization of racemic amines. This deracemization process is normally achieved by discrete sequential oxidation/reduction steps using a separate enantiomer-specific biocatalyst and metal catalyst, respectively. Here, use of E. coli cultures carrying the cloned monoamine oxidase gene and nanoscale bioreduced Pd(0) particles was used successfully for the conversion of racemic 1-methyltetrahydroisoquinoline (MTQ) to (R)-MTQ, via the intermediate 1-methyl-3,4-dihydroisoquinoline, with an enantiomeric excess of up to 96%. There was no loss of catalyst activity following the five rounds of oxidation and reduction, and importantly, there was minimal loss of palladium into the reaction supernatant. This first demonstration of a whole cell biometallic catalyst mixture for "single-pot", multistep reactions opens up the way for a wide range of integrated processes, offering a scalable and highly flexible platform technology.