Yeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production
Yeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production
复制标题
DOI：
10.1021/acssynbio.7b00396
复制
发表时间：
2018-03-01
影响因子：
4.7
通讯作者：
Lu, Timothy K.
中科院分区：
文献类型：
--
作者：
Cao, Jicong;de la Fuente-Nunez, Cesar;Lu, Timothy K.
抗生素耐药性是我们社会中最具挑战性的全球健康威胁之一。抗菌肽（AMP）是治疗耐药感染的传统抗生素的有前景的替代品。然而，它们受到高制造成本的限制。工程生物体代表了一种以廉价方式生产此类分子的有前途的方法。在这里，我们利用融合蛋白方法对巴斯德毕赤酵母进行基因改造，以产生原型 AMP apidaecin Ia，该方法利用了人血清白蛋白的有益特性（例如稳定性）。该肽成功地从融合蛋白构建体中分离、纯化，并被证明具有抗大肠杆菌的生物活性。为了证明这种方法作为 AMP 的制造解决方案，我们扩大了生物反应器的生产规模，以产生高 AMP 产量。我们预计该系统可以改进 AMP 生物制造平台。
Antibiotic resistance is one of the most challenging global health threats in our society. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics for the treatment of drug-resistant infections. However, they are limited by their high manufacturing cost. Engineering living organisms represents a promising approach to produce such molecules in an inexpensive manner. Here, we genetically modified the yeast Pichia pastoris to produce the prototypical AMP apidaecin Ia using a fusion protein approach that leverages the beneficial properties (e.g., stability) of human serum albumin. The peptide was successfully isolated from the fusion protein construct, purified, and demonstrated to have bioactivity against Escherichia coli. To demonstrate this approach as a manufacturing solution to AMPs, we scaled-up production in bioreactors to generate high AMP yields. We envision that this system could lead to improved AMP biomanufacturing platforms.