中文摘要：通过噬菌体基因工程能开发出高性能的生物传感器。本文展示了对含基因工程噬菌体的气体炸药具有高选择性的快速响应光学生物传感器。该传感器在噬菌体中配备了肽序列，在可见光条件下与挥发性有机化合物(VOCs)的相互作用最佳。为了克服传统的问题，本研究通过大量经验计算，建立了一个包含8000个三肽的大型数据库，并筛选出对三个化学类别的九种VOCs的最佳电子鼻传感性能。第一性原理密度泛函理论（DFT）计算揭示了在电子能带结构水平上化学亲和性和光学性质变化之间的潜在关联。通过体外实验设计和用5个筛出的三肽序列转基因噬菌体和野生型噬菌体的多阵列传感器测试，验证了以上计算结果。由聚类分析评估的分类成功率与计算结果高度一致。本光学生物传感器对爆炸性挥发有机物的传感分辨率达到了1 ppb水平，远远超过了传统生物传感器。基于大数据计算预测和现场实验验证的系统相互作用可以为高性能生物传感器提供智能设计原则。
外文摘要：Genetic engineering of a bacteriophage is a promising way to develop a highly functional biosensor. Almost countless configurational degree of freedom in the manipulation, considerable uncertainty and cost involved with the approach, however, have been huddles for the objective. In this paper, we demonstrate rapidly responding optical biosensor with high selectivity toward gaseous explosives with genetically engineered phages. The sensors are equipped with peptide sequences in phages optimally interacting with the volatile organic compounds (VOCs) in visible light regime. To overcome the conventional issues, we use extensive utilization of empirical calculations to construct a large database of 8000 tripeptides and screen the best for electronic nose sensing performance toward nine VOCs belonging to three chemical classes. First-principles density functional theory (DFT) calculations unveil underlying correlations between the chemical affinity and optical property change on an electronic band structure level. The computational outcomes are validated by in vitro experimental design and testing of multiarray sensors using genetically modified phage implemented with five selected tripeptide sequences and wild-type phages. The classification success rates estimated from hierarchical cluster analysis are shown to be very consistent with the calculations. Our optical biosensor demonstrates a 1 ppb level of sensing resolution for explosive VOCs, which is a substantial improvement over conventional biosensor. The systematic interplay of big data-based computational prediction and in situ experimental validation can provide smart design principles for unconventionally outstanding biosensors.
外文关键词：Virtual screening；First-principles calculations；M13 bacteriophage； Electronic nose；Volatile organic compounds
作者：Park, J；Lee, JM；Chun, H；Lee, Y；Hong, SJ；Jung, H；Kim, YJ；Kim, WG；Devaraj, V；Choi, EJ；Oh, JW；Han, B
作者单位：Yonsei Univ；Pusan Natl Univ
期刊名称：BIOSENSORS & BIOELECTRONICS
期刊影响因子：10.257
出版年份：2021
出版刊次：177
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