Antibiotics (Basel), 2020, 9(4)

Deep Functional Profiling Facilitates the Evaluation of the Antibacterial Potential of the Antibiotic Amicoumacin.

The global spread of antibiotic resistance is forcing the scientific community to find new molecular strategies to counteract it. Deep functional profiling of microbiomes provides an alternative source for the discovery of novel antibiotic producers and probiotics. Recently, we implemented this ultrahigh-throughput screening approach for the isolation of strains efficiently producing the ribosome-targeting antibiotic amicoumacin A (Ami). Proteomics and metabolomics revealed essential insight into the activation of Ami biosynthesis. Here, we applied omics to boost Ami biosynthesis, providing the optimized cultivation conditions for high-scale production of Ami. Ami displayed a pronounced activity against and , including methicillin-resistant (MRSA) strains, which was determined using both classical and massive single-cell microfluidic assays. However, the practical application of Ami is limited by its high cytotoxicity and particularly low stability. The former is associated with its self-lactonization, serving as an improvised intermediate state of Ami hydrolysis. This intramolecular reaction decreases Ami half-life at physiological conditions to less than 2 h, which is unprecedented for a terminal amide. While we speculate that the instability of Ami is essential for ecology, we believe that its stable analogs represent attractive lead compounds both for antibiotic discovery and for anticancer drug development.

Terekhov SS, Nazarov AS, Mokrushina YA, Baranova MN, Potapova NA, Malakhova MV, Ilina EN, Smirnov IV, Gabibov AG

IBCH: 8516
Ссылка на статью в журнале: https://www.mdpi.com/2079-6382/9/4/157
Кол-во цитирований на 03.2021: 4
Данные статьи проверены модераторами 2020-04-11

Список научных проектов, где отмечена публикация

  1. - (January 6, 2019 — December 31, 2020). Terekhov S.S.. Grant, RFBR.
  2. - (August 7, 2018 — December 7, 2021). Smirnov I.V.. Grant, RFBR.