期刊
ACS SYNTHETIC BIOLOGY
卷 10, 期 7, 页码 1703-1714出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.1c00080
关键词
lanthipeptide; nisin; antimicrobial activity; Lactococcus; Staphylococcus; thanatin
资金
- Netherlands Organization for Scientific Research (NWO), research program TTW [17241]
This study demonstrates the synthesis of novel macrocyclic lanthipeptides using thanatin and rip-thanatin as templates, showing selective antimicrobial activity against S. aureus, including an antibiotic-resistant MRSA strain. The hybrid peptides of nisin(1-20) and ripcin, ripcin B-G, which are inactive against Gram-negative pathogens, exhibited substantial antimicrobial activity against tested Gram-negative pathogens and were highly resistant against the nisin resistance protein NSR.
Lanthipeptides are (methyl)lanthionine ring-containing ribosomally synthesized and post-translationally modified peptides (RiPPs). Many lanthipeptides show strong antimicrobial activity against bacterial pathogens, including antibiotic-resistant bacterial pathogens. The group of disulfide-bond-containing antimicrobial peptides (AMPs) is well-known in nature and forms a rich source of templates for the production of novel peptides with corresponding (methyl)lanthionine analogues instead of disulfides. Here, we show that novel macrocyclic lanthipeptides (termed thanacin and ripcin) can be synthesized using the known antimicrobials thanatin and rip-thanatin as templates. Notably, the synthesized nisin(1-20)-ripcin hybrid lanthipeptides (ripcin B-G) showed selective antimicrobial activity against S. aureus, including an antibiotic-resistant MRSA strain. Interestingly, ripcin B-G, which are hybrid peptides of nisin(1-20) and ripcin that are each inactive against Gram-negative pathogens, showed substantial antimicrobial activity against the tested Gram-negative pathogens. Moreover, ripcin B-G was highly resistant against the nisin resistance protein (NSR; a peptidase that removes the C-terminal 6 amino acids of nisin and strongly reduces its antimicrobial activity), opposed to nisin itself. This study provides an example of converting disulfide-bond-based AMPs into (methyl)lanthionine-based macrocyclic hybrid lanthipeptides and can yield antimicrobial peptides with selective antimicrobial activity against S. aureus.
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