Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Drug Design and Development Research Group (DDDRG), Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Mol Biotechnol. 2021 Apr;63(4):316-326. doi: 10.1007/s12033-021-00304-z. Epub 2021 Feb 9.
Prenylation of aromatic natural products by membrane-bound prenyltransferases (PTs) is an important biosynthesis step of many bioactive compounds. At present, only a few plant flavonoid-related PT genes have been functionally characterized, mainly due to the difficulties of expressing these membrane proteins. Rapid and effective methods to produce functional plant membrane proteins are thus indispensable. Here, we evaluated expression systems through cell-based and cell-free approaches to express Boesenbergia rotunda BrPT2 encoding a membrane-bound prenyltransferase. We attempted to express BrPT2 in Escherichia coli and tobacco plants but failed to detect this protein using the Western-blot technique, whereas an intact single band of 43 kDa was detected when BrPT2 was expressed using a cell-free protein synthesis system (PURE). Under in vitro enzymatic condition, the synthesized BrPT2 successfully catalyzed pinostrobin chalcone to pinostrobin. Molecular docking analysis showed that pinostrobin chalcone interacts with BrPT2 at two cavities: (1) the main binding site at the central cavity and (2) the allosteric binding site located away from the central cavity. Our findings suggest that cell-free protein synthesis could be an alternative for rapid production of valuable difficult-to-express membrane proteins.
芳香天然产物的膜结合 prenyltransferase(PTs)的 prenylation 是许多生物活性化合物的重要生物合成步骤。目前,仅对少数与植物类黄酮相关的 PT 基因进行了功能表征,主要是由于这些膜蛋白的表达存在困难。因此,快速有效的方法来生产功能性植物膜蛋白是必不可少的。在这里,我们通过基于细胞和无细胞的方法来评估表达系统,以表达编码膜结合 prenyltransferase 的 Boesenbergia rotunda BrPT2。我们尝试在大肠杆菌和烟草植物中表达 BrPT2,但使用 Western-blot 技术未能检测到该蛋白,而当使用无细胞蛋白合成系统(PURE)表达 BrPT2 时,则检测到完整的 43 kDa 单一条带。在体外酶促条件下,合成的 BrPT2 成功地催化了 pinostrobin chalcone 转化为 pinostrobin。分子对接分析表明,pinostrobin chalcone 在两个腔室与 BrPT2 相互作用:(1)中央腔的主要结合位点,(2)远离中央腔的变构结合位点。我们的研究结果表明,无细胞蛋白合成可能是快速生产有价值的难以表达的膜蛋白的替代方法。