Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, U.K.
Asymptote, Cytiva, Chivers Way, Cambridge CB24 9BZ, U.K.
J Am Chem Soc. 2023 Apr 26;145(16):8794-8799. doi: 10.1021/jacs.3c01874. Epub 2023 Apr 17.
Bioprocessing and biotechnology exploit microorganisms (such as bacteria) for the production of chemicals, biologics, therapies, and food. A major unmet challenge is that bacteriophage (phage) contamination compromises products and necessitates shut-downs and extensive decontamination using nonspecific disinfectants. Here we demonstrate that poly(acrylic acid) prevents phage-induced killing of bacterial hosts, prevents phage replication, and that induction of recombinant protein expression is not affected by the presence of the polymer. Poly(acrylic acid) was more active than poly(methacrylic acid), and poly(styrenesulfonate) had no activity showing the importance of the carboxylic acids. Initial evidence supported a virustatic, not virucidal, mechanism of action. This simple, low-cost, mass-produced additive offers a practical, scalable, and easy to implement solution to reduce phage contamination.
生物加工和生物技术利用微生物(如细菌)来生产化学品、生物制剂、疗法和食品。一个主要的未满足的挑战是噬菌体(噬菌体)污染会损害产品,需要使用非特异性消毒剂进行停产和广泛消毒。在这里,我们证明聚丙烯酸可以防止噬菌体诱导的细菌宿主死亡,防止噬菌体复制,并且聚合物的存在不会影响重组蛋白表达的诱导。聚丙烯酸比聚甲基丙烯酸更有效,而聚苯乙烯磺酸盐没有活性,这表明羧酸的重要性。初步证据支持一种具有病毒抑制而非病毒杀灭作用的作用机制。这种简单、低成本、大规模生产的添加剂为减少噬菌体污染提供了一种实用、可扩展且易于实施的解决方案。