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Exploring the Specificity of Extracellular Wastewater Peptidases to Improve the Design of Sustainable Peptide-Based Antibiotics.
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2020-08-13 , DOI: 10.1021/acs.est.0c02564 Michael T Zumstein 1, 2 , Jeffrey J Werner 3 , Damian E Helbling 1
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2020-08-13 , DOI: 10.1021/acs.est.0c02564 Michael T Zumstein 1, 2 , Jeffrey J Werner 3 , Damian E Helbling 1
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New antimicrobial peptides are emerging as promising alternatives to conventional antibiotics because of their specificity for target pathogens and their potential to be rapidly hydrolyzed (i.e., inactivated) by extracellular peptidases during biological wastewater treatment, thereby limiting the emergence and propagation of antibiotic resistance in the environment. However, little is known about the specificity of extracellular peptidases derived from wastewater microbial communities, which is a major impediment for the design of sustainable peptide-based antibiotics that can be hydrolyzed by wastewater peptidases. We used a set of natural peptides to explore the specificity of dissolved extracellular wastewater peptidases. We found that enzyme-catalyzed hydrolysis occurred at specific sites and that a subset of these hydrolyses was conserved across enzyme pools derived from three independent wastewater microbial communities. An analysis of the amino-acid residues flanking the hydrolyzed bonds revealed a set of residue motifs that were linked to enzyme-catalyzed hydrolysis and are therefore candidates for incorporation into new and sustainable peptide-based antibiotics.
中文翻译：
探索细胞外废水肽酶的特异性，以改善基于肽的可持续抗生素的设计。
新抗菌肽正在成为有前途的替代品被迅速水解，因为它们的特异性靶病原体及其潜在的常规抗生素（即（在生物废水处理过程中被细胞外肽酶灭活），从而限制了环境中抗生素抗性的出现和传播。然而，关于源自废水微生物群落的细胞外肽酶的特异性知之甚少，这是设计可被废水肽酶水解的可持续的基于肽的抗生素的主要障碍。我们使用了一组天然肽来探索溶解的细胞外废水肽酶的特异性。我们发现，酶催化的水解发生在特定的位置，并且这些水解的一个子集在源自三个独立的废水微生物群落的酶池之间是保守的。
更新日期：2020-09-15
中文翻译：
探索细胞外废水肽酶的特异性，以改善基于肽的可持续抗生素的设计。
新抗菌肽正在成为有前途的替代品被迅速水解，因为它们的特异性靶病原体及其潜在的常规抗生素（即（在生物废水处理过程中被细胞外肽酶灭活），从而限制了环境中抗生素抗性的出现和传播。然而，关于源自废水微生物群落的细胞外肽酶的特异性知之甚少，这是设计可被废水肽酶水解的可持续的基于肽的抗生素的主要障碍。我们使用了一组天然肽来探索溶解的细胞外废水肽酶的特异性。我们发现，酶催化的水解发生在特定的位置，并且这些水解的一个子集在源自三个独立的废水微生物群落的酶池之间是保守的。
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