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Molecular insights into the antifungal mechanism of bacilysin
Authors:Tao?Wang  author-information"  >  author-information__contact u-icon-before"  >  mailto:tao-wang@zju.edu.cn"   title="  tao-wang@zju.edu.cn"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author,Xiao-huan?Liu,Mian-Bin?Wu  author-information"  >  author-information__contact u-icon-before"  >  mailto:wumb@zju.edu.cn"   title="  wumb@zju.edu.cn"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author,Shun?Ge
Affiliation:1.School of Biological Science,Jining Medical University,Jining,China;2.Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering,Zhejiang University,Hangzhou,China
Abstract:Bacilysin is one of the simplest antimicrobial peptides and has drawn great attention for its excellent performance against Candida albicans. In this study, the antifungal mechanism of bacilysin was investigated. The target enzyme glucosamine-6-phosphate synthase (GFA) was expressed heterologously in Escherichia coli and its inhibition by bacilysin and derivatives was studied. It was concluded that bacilysin could be hydrolyzed by a proteinase of C. albicans, and that the released product, anticapsin, then inhibited the aminotransferase activity of GFA. This result was verified by molecular simulation, and the interaction mode of anticapsin with GFA was detailed, which provides data for the development of novel antifungal drugs. Transport of bacilysin into fungal cells was also simulated and it was shown that bacilysin is more readily transported into cells than anticapsin. Thus, our findings support a mechanism whereby bacilysin is transported into fungal pathogens, hydrolyzed to anticapsin, which then inhibits GFA.
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