Ryu Jaewook, Lee Ukjin, Park Jiye, Yoo Do-Hyun, Ahn Jung Hoon
Korea Science Academy of KAIST, Busanjin-Gu, Busan, South Korea.
Korea Science Academy of KAIST, Busanjin-Gu, Busan, South Korea
Appl Environ Microbiol. 2015 Mar;81(5):1744-53. doi: 10.1128/AEM.03514-14. Epub 2014 Dec 29.
Pseudomonas fluorescens is an efficient platform for recombinant protein production. P. fluorescens has an ABC transporter secreting endogenous thermostable lipase (TliA) and protease, which can be exploited to transport recombinant proteins across the cell membrane. In this study, the expression vector pDART was constructed by inserting tliDEF, genes encoding the ABC transporter, along with the construct of the lipase ABC transporter recognition domain (LARD), into pDSK519, a widely used shuttle vector. When the gene for the target protein was inserted into the vector, the C-terminally fused LARD allowed it to be secreted through the ABC transporter into the extracellular medium. After secretion of the fused target protein, the LARD containing a hydrophobic C terminus enabled its purification through hydrophobic interaction chromatography (HIC) using a methyl-Sepharose column. Alkaline phosphatase (AP) and green fluorescent protein (GFP) were used to validate the expression, export, and purification of target proteins by the pDART system. Both proteins were secreted into the extracellular medium in P. fluorescens. In particular, AP was secreted in several Pseudomonas species with its enzymatic activity in extracellular media. Furthermore, purification of the target protein using HIC yielded some degree of AP and GFP purification, where AP was purified to almost a single product. The pDART system will provide greater convenience for the secretory production and purification of recombinant proteins in Gram-negative bacteria, such as Pseudomonas species.
荧光假单胞菌是重组蛋白生产的高效平台。荧光假单胞菌具有一种ABC转运蛋白,可分泌内源性耐热脂肪酶(TliA)和蛋白酶,可利用该转运蛋白将重组蛋白转运穿过细胞膜。在本研究中,通过将编码ABC转运蛋白的基因tliDEF以及脂肪酶ABC转运蛋白识别域(LARD)构建体插入广泛使用的穿梭载体pDSK519中,构建了表达载体pDART。当将目标蛋白的基因插入载体时,C末端融合的LARD使其能够通过ABC转运蛋白分泌到细胞外培养基中。融合的目标蛋白分泌后,含有疏水C末端的LARD能够通过使用甲基琼脂糖柱的疏水相互作用色谱法(HIC)进行纯化。使用碱性磷酸酶(AP)和绿色荧光蛋白(GFP)来验证pDART系统对目标蛋白的表达、输出和纯化。两种蛋白均在荧光假单胞菌中分泌到细胞外培养基中。特别是,AP在几种假单胞菌属中分泌,并在细胞外培养基中具有酶活性。此外,使用HIC纯化目标蛋白可对AP和GFP进行一定程度的纯化,其中AP几乎被纯化为单一产物。pDART系统将为革兰氏阴性菌(如假单胞菌属)中重组蛋白的分泌生产和纯化提供更大的便利。