Lipid interactions couple turnercyclamycin antibacterial activity with carbohydrate-active enzyme packaging in membrane vesicles.
- 1Department of Medicinal Chemistry, University of Utah Salt Lake City UT 84112 USA [email protected].
- 2Johns Hopkins Applied Physics Laboratory Laurel MD 20723 USA.
- 3Ocean Genome Legacy Center, Northeastern University Nahant MA 01908 USA [email protected].
Abstract
Turnercyclamycins from shipworm-symbiotic bacteria are lipopeptides with promise for targeting bacterial infections. Their mechanisms of action and resistance suggest an essential role for lipid interactions. We purified analogs with lipid chain lengths ranging from C12 to C16 and tested them against E. coli, with and without ΔmlaA, which confers resistance to turnercyclamycin B but not to A. A C14 fatty acid provided the optimal side chain for activity against both strains. We disrupted a hydroxylating enzyme in Teredinibacter turnerae T7901, generated an unnatural analog, assigned specific activity to one of the tailoring enzymes, and genetically validated the tur biosynthetic pathway. By genome mining, we found structural homologs in Gynuella sunshinyii YC6258. Finally, we found that turnercyclamycins are selectively associated with T. turnerae membrane vesicles (MVs), linking these antibiotics to natural transport mechanisms. These results establish that lipid length determines turnercyclamycin antibacterial activity and suggest that the same interactions also govern ecological transport through MVs.
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BibTeX
@article{miller2026lipid,
title = {{Lipid interactions couple turnercyclamycin antibacterial activity with carbohydrate-active enzyme packaging in membrane vesicles.}},
author = {Bailey W Miller and Albebson L Lim and Mark T Gasser and Zhenjian Lin and Daniel L Distel and Eric W Schmidt},
journal = {RSC chemical biology},
year = {2026},
month = oct,
doi = {10.1039/d6cb00220j},
url = {https://europepmc.org/article/MED/42903939},
note = {CC BY},
}
RIS
TY - JOUR
TI - Lipid interactions couple turnercyclamycin antibacterial activity with carbohydrate-active enzyme packaging in membrane vesicles.
AU - Bailey W Miller
AU - Albebson L Lim
AU - Mark T Gasser
AU - Zhenjian Lin
AU - Daniel L Distel
AU - Eric W Schmidt
PY - 2026
DA - 2026/10/09
JO - RSC chemical biology
DO - 10.1039/d6cb00220j
UR - https://europepmc.org/article/MED/42903939
AB - Turnercyclamycins from shipworm-symbiotic bacteria are lipopeptides with promise for targeting bacterial infections. Their mechanisms of action and resistance suggest an essential role for lipid interactions. We purified analogs with lipid chain lengths ranging from C12 to C16 and tested them against E. coli, with and without ΔmlaA, which confers resistance to turnercyclamycin B but not to A. A C14 fatty acid provided the optimal side chain for activity against both strains. We disrupted a hydroxylating enzyme in Teredinibacter turnerae T7901, generated an unnatural analog, assigned specific activity to one of the tailoring enzymes, and genetically validated the tur biosynthetic pathway. By genome mining, we found structural homologs in Gynuella sunshinyii YC6258. Finally, we found that turnercyclamycins are selectively associated with T. turnerae membrane vesicles (MVs), linking these antibiotics to natural transport mechanisms. These results establish that lipid length determines turnercyclamycin antibacterial activity and suggest that the same interactions also govern ecological transport through MVs.
SN - 2633-0679
ER -