Brown, E. D. & Wright, G. D. Antibacterial drug discovery in the resistance era. Nature 529, 336–343 (2016).

CAS  PubMed  Article  Google Scholar 

Lewis, K. The science of antibiotic discovery. Cell 181, 29–45 (2020).

CAS  PubMed  Article  Google Scholar 

Ling, L. L. et al. A new antibiotic kills pathogens without detectable resistance. Nature 517, 455–459 (2015).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Tacconelli, E. et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis. 18, 318–327 (2018).

PubMed  Article  Google Scholar 

Zgurskaya, H. I., Rybenkov, V. V., Krishnamoorthy, G. & Leus, I. V. Trans-envelope multidrug efflux pumps of Gram-negative bacteria and their synergism with the outer membrane barrier. Res. Microbiol. 169, 351–356 (2018).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Richter, M. F. et al. Predictive compound accumulation rules yield a broad-spectrum antibiotic. Nature 545, 299–304 (2017).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Parker, E. N. et al. Implementation of permeation rules leads to a FabI inhibitor with activity against Gram-negative pathogens. Nat. Microbiol. 5, 67–75 (2020).

CAS  PubMed  Article  Google Scholar 

Gavrish, E. et al. Lassomycin, a ribosomally synthesized cyclic peptide, kills Mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2. Chem. Biol. 21, 509–518 (2014).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Quigley, J. et al. Novel antimicrobials from uncultured bacteria acting against Mycobacterium tuberculosis. mBio https://doi.org/10.1128/mBio.01516-20 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Shahsavari, N. et al. A silent operon of Photorhabdus luminescens encodes a prodrug mimic of GTP. mBio https://doi.org/10.1128/mbio.00700-22 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Leimer, N. et al. A selective antibiotic for lyme disease. Cell https://doi.org/10.1016/j.cell.2021.09.011 (2021).

Article  PubMed  Google Scholar 

Crawford, J. M. & Clardy, J. Bacterial symbionts and natural products. Chem. Commun. 47, 7559–7566 (2011).

CAS  Article  Google Scholar 

Tobias, N. J., Shi, Y. M. & Bode, H. B. Refining the natural product repertoire in entomopathogenic bacteria. Trends Microbiol. 26, 833–840 (2018).

CAS  PubMed  Article  Google Scholar 

Imai, Y. et al. A new antibiotic selectively kills Gram-negative pathogens. Nature 576, 459–464 (2019).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Kaur, H. et al. The antibiotic darobactin mimics a beta-strand to inhibit outer membrane insertase. Nature 593, 125–129 (2021).

CAS  PubMed  Article  Google Scholar 

Rutledge, P. J. & Challis, G. L. Discovery of microbial natural products by activation of silent biosynthetic gene clusters. Nat. Rev. Microbiol. 13, 509–523 (2015).

CAS  PubMed  Article  Google Scholar 

Hover, B. M. et al. Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens. Nat. Microbiol. 3, 415–422 (2018).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Stokes, J. M. et al. A deep learning approach to antibiotic discovery. Cell 180, 688–702.e13 (2020).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).

CAS  PubMed  Article  Google Scholar 

Santos-Aberturas, J. et al. Uncovering the unexplored diversity of thioamidated ribosomal peptides in Actinobacteria using the RiPPER genome mining tool. Nucleic Acids Res. 47, 4624–4637 (2019).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Sievers, F. et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).

PubMed  PubMed Central  Article  Google Scholar 

Grell, T. A., Goldman, P. J. & Drennan, C. L. SPASM and twitch domains in S-adenosylmethionine (SAM) radical enzymes. J. Biol. Chem. 290, 3964–3971 (2015).

CAS  PubMed  Article  Google Scholar 

Montalbán-López, M. et al. New developments in RiPP discovery, enzymology and engineering. Nat. Prod. Rep. 38, 130–239 (2021).

PubMed  Article  Google Scholar 

Akiva, E. et al. The structure–function linkage database. Nucleic Acids Res. 42, D521–D530 (2014).

CAS  PubMed  Article  Google Scholar 

Grove, T. L., Lee, K. H., St Clair, J., Krebs, C. & Booker, S. J. In vitro characterization of AtsB, a radical SAM formylglycine-generating enzyme that contains three [4Fe-4S] clusters. Biochemistry 47, 7523–7538 (2008).

CAS  PubMed  Article  Google Scholar 

Goldman, P. J. et al. X-ray structure of an AdoMet radical activase reveals an anaerobic solution for formylglycine posttranslational modification. Proc. Natl Acad. Sci. USA 110, 8519–8524 (2013).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Zhang, Q., Mo, T., Ding, W., Han, Y. & Deng, Z. The research on post-translational modification of RiPPs Xye catalyzed by CyFE PacB. Synth. Biol. J. https://doi.org/10.12211/2096-8280.2021-080 (2021).

Article  Google Scholar 

Vesth, T. et al. Veillonella, firmicutes: microbes disguised as gram negatives. Stand. Genom. Sci. 9, 431–448 (2013).

Article  Google Scholar 

Antunes, L. C. et al. Phylogenomic analysis supports the ancestral presence of LPS-outer membranes in the Firmicutes. eLife 5, e14589 (2016).

PubMed  PubMed Central  Article  Google Scholar 

Wang, M. et al. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat. Biotechnol. 34, 828–837 (2016).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Jones, C. G. et al. The CryoEM method MicroED as a powerful tool for small molecule structure determination. ACS Cent. Sci. 4, 1587–1592 (2018).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Haupert, L. M. & Simpson, G. J. Screening of protein crystallization trials by second order nonlinear optical imaging of chiral crystals (SONICC). Methods 55, 379–386 (2011).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Nguyen, T. Q. N. et al. Post-translational formation of strained cyclophanes in bacteria. Nat. Chem. 12, 1042–1053 (2020).

CAS  PubMed  Article  Google Scholar 

Matsunaga, S. & Fusetani, N. Theonellamides AE, cytotoxic bicyclic peptides, from a marine sponge Theonella sp. J. Org. Chem. 60, 1177–1181 (1995).

CAS  Article  Google Scholar 

Nicolet, Y. Structure–function relationships of radical SAM enzymes. Nat. Catal. 3, 337–350 (2020).

CAS  Article  Google Scholar 

Benjdia, A., Balty, C. & Berteau, O. Radical SAM enzymes in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs). Front. Chem. 5, 87 (2017).

PubMed  PubMed Central  Article  Google Scholar 

Yu, D. et al. An efficient recombination system for chromosome engineering in Escherichia coli. Proc. Natl Acad. Sci. USA 97, 5978–5983 (2000).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Datsenko, K. A. & Wanner, B. L. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc. Natl Acad. Sci. USA 97, 6640–6645 (2000).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Kaur, H. et al. Identification of conformation-selective nanobodies against the membrane protein insertase BamA by an integrated structural biology approach. J. Biomol. NMR https://doi.org/10.1007/s10858-019-00250-8 (2019).

Article