study of syn-BNPs that are inspired by un-
explored BGC families should prove to be a
productive strategy for identifying distinctive
scaffolds that can serve as lead structures for
developing antibiotics with diverse MOAs.
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ACKNOWLEDGMENTS
We thank J. C. Vederas for providing synthetic lipid II(lys), the
CDC for providing vancomycin-resistant strains, the Rockefeller
University High Throughput Screening and Spectroscopy Resource
Center for assistance with isothermal titration calorimetry
experiments, the Rockefeller University Comparative BioscienceCenter for help with animal studies, and the Rockefeller
University Electron MicroscopyResource Center for collecting
scanning electron microscope data.Funding:This work was
supported by the National Institutes of Health (grants
1U19AI142731 and 5R35GM122559).Author contributions:
S.F.B. and Z.W. designed the study and analyzed the data. Z.W.
performed the biochemical experiments. B.K. performed the
peptide synthesis. Z.W. and Y.H. performed the bioinformatic
analysis. M.Z. performed the pharmacokinetics assay. S.F.B. and
Z.W. designed the animal study. S.F.B. and Z.W. prepared the
manuscript. All authors were involved in discussing the
results and reviewing the manuscript.Competing interests:A
patent covering the structure and activity of cilagicin has been
filed by Rockefeller University. S.F.B. consulted for Lodo
Therapeutics and Zymergen and has Zymergen stock options.
The remaining authors declare no competing interests.
Data and materials availability:Thegenomesequences
of P. mucilaginosusK02 and KNP414 are available in GenBank
under accession numbers NC_017672.3 and NC_015690.1,
respectively. BGCs were collected from antiSMASH-db
(version 2.0). The Perl script used to identify lipopeptide
BGCs can be accessed through Zenodo ( 41 ). NMR spectra for
cilagicin and cilagicin BP are presented in the supplementary
materials. All data are available in the main text or the
supplementary materials.License information:Copyright ©
2022 the authors, some rights reserved; exclusive licensee
American Association for the Advancement of Science. No claim
to original US government works. https://www.science.org/
about/science-licenses-journal-article-reuseSUPPLEMENTARY MATERIALS
science.org/doi/10.1126/science.abn4213
Materials and Methods
Figs. S1 to S9
Tables S1 to S7
References ( 42 – 45 )
MDAR Reproducibility Checklist
View/request a protocol for this paper fromBio-protocol.Submitted 29 November 2021; accepted 6 April 2022
10.1126/science.abn4213Wanget al., Science 376 , 991–996 (2022) 27 May 2022 6of6
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