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Yeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-01-24 00:00:00 , DOI: 10.1021/acssynbio.7b00396
Jicong Cao 1, 2, 3 , Cesar de la Fuente-Nunez 1, 2, 3 , Rui Wen Ou 4 , Marcelo Der Torossian Torres 1, 2, 5 , Santosh G. Pande 6 , Anthony J. Sinskey 4 , Timothy K. Lu 1, 2, 3
Affiliation  

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.

中文翻译:

基于酵母的抗菌肽合成生物学平台

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(AMPs)代表了用于治疗耐药性感染的常规抗生素的有前途的替代品。但是,它们受到高制造成本的限制。工程化的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,我们使用融合蛋白方法对酵母巴斯德毕赤酵母进行了基因修饰,以产生原型AMP杀青霉素Ia,该蛋白利用了人类血清白蛋白的有益特性(例如,稳定性)。从融合蛋白构建体中成功分离出该肽,进行了纯化,并证明对大肠杆菌具有生物活性。。为了展示这种方法作为AMP的生产解决方案,我们扩大了生物反应器的生产规模,以产生较高的AMP产量。我们设想该系统可以改善AMP生物制造平台。
更新日期:2018-01-24
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