Gustavsson Martin, Muraleedharan Madhu Nair, Larsson Gen
Division of Industrial Biotechnology, School of Biotechnology, Royal Institute of Technology (KTH), Stockholm, Sweden.
Appl Environ Microbiol. 2014 Apr;80(7):2293-8. doi: 10.1128/AEM.03678-13. Epub 2014 Jan 31.
Chiral amines are important for the chemical and pharmaceutical industries, and there is rapidly growing interest to use transaminases for their synthesis. Since the cost of the enzyme is an important factor for process economy, the use of whole-cell biocatalysts is attractive, since expensive purification and immobilization steps can be avoided. Display of the protein on the cell surface provides a possible way to reduce the mass transfer limitations of such biocatalysts. However, transaminases need to dimerize in order to become active, and furthermore, they require the cofactor pyridoxal phosphate; consequently, successful transaminase surface expression has not been reported thus far. In this work, we produced an Arthrobacter citreus ω-transaminase in Escherichia coli using a surface display vector based on the autotransporter adhesin involved in diffuse adherence (AIDA-I), which has previously been used for display of dimeric proteins. The correct localization of the transaminase in the E. coli outer membrane and its orientation toward the cell exterior were verified. Furthermore, transaminase activity was detected exclusively in the outer membrane protein fraction, showing that successful dimerization had occurred. The transaminase was found to be present in both full-length and proteolytically degraded forms. The removal of this proteolysis is considered to be the main obstacle to achieving sufficient whole-cell transaminase activity.
手性胺对化学和制药行业很重要,人们对使用转氨酶来合成手性胺的兴趣正在迅速增长。由于酶的成本是影响工艺经济性的一个重要因素,因此使用全细胞生物催化剂很有吸引力,因为可以避免昂贵的纯化和固定步骤。将蛋白质展示在细胞表面为减少此类生物催化剂的传质限制提供了一种可能的方法。然而,转氨酶需要二聚化才能变得有活性,此外,它们还需要辅因子磷酸吡哆醛;因此,迄今为止尚未有成功的转氨酶表面表达的报道。在这项工作中,我们使用基于参与弥散黏附的自转运黏附素(AIDA-I)的表面展示载体在大肠杆菌中生产了柠檬节杆菌ω-转氨酶,该载体此前已用于展示二聚体蛋白。验证了转氨酶在大肠杆菌外膜中的正确定位及其朝向细胞外的方向。此外,仅在外膜蛋白组分中检测到转氨酶活性,表明已成功发生二聚化。发现转氨酶以全长和蛋白水解降解形式存在。消除这种蛋白水解作用被认为是实现足够的全细胞转氨酶活性的主要障碍。