Metagenomic domain substitution for the high-throughput modification of nonribosomal peptides

Newman, D. J. & Cragg, G. M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J. Nat. Prod. 83, 770–803 (2020).

Article  CAS  PubMed  Google Scholar 

Cook, M. A. & Wright, G. D. The past, present, and future of antibiotics. Sci. Transl. Med. 14, eabo7793 (2022).

Article  CAS  PubMed  Google Scholar 

Felnagle, E. A. et al. Nonribosomal peptide synthetases involved in the production of medically relevant natural products. Mol. Pharm. 5, 191–211 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kunakom, S. & Eustaquio, A. S. Natural products and synthetic biology: where we are and where we need to go. mSystems 4, e00113-19 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Abbood, N., Präve, L., Bozhueyuek, K. A. J. & Bode, H. B. A practical guideline to engineering nonribosomal peptide synthetases. Methods Mol. Biol. 2670, 219–234 (2023).

Article  PubMed  Google Scholar 

WHO model list of essential medicines. World Health Organization www.who.int/publications/i/item/WHO-MHP-HPS-EML-2021.02 (2021).

Baltz, R. H. Renaissance in antibacterial discovery from actinomycetes. Curr. Opin. Pharmacol. 8, 557–563 (2008).

Article  CAS  PubMed  Google Scholar 

Bauman, K. D., Butler, K. S., Moore, B. S. & Chekan, J. R. Genome mining methods to discover bioactive natural products. Nat. Prod. Rep. 38, 2100–2129 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Milshteyn, A., Schneider, J. S. & Brady, S. F. Mining the metabiome: identifying novel natural products from microbial communities. Chem. Biol. 21, 1211–1223 (2014).

Article  CAS  PubMed  PubMed Central  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).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Craig, J. W., Chang, F. Y., Kim, J. H., Obiajulu, S. C. & Brady, S. F. Expanding small-molecule functional metagenomics through parallel screening of broad-host-range cosmid environmental DNA libraries in diverse proteobacteria. Appl. Environ. Microbiol. 76, 1633–1641 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brown, A. S., Calcott, M. J., Owen, J. G. & Ackerley, D. F. Structural, functional and evolutionary perspectives on effective re-engineering of non-ribosomal peptide synthetase assembly lines. Nat. Prod. Rep. 35, 1210–1228 (2018).

Article  CAS  PubMed  Google Scholar 

Winn, M., Fyans, J. K., Zhuo, Y. & Micklefield, J. Recent advances in engineering nonribosomal peptide assembly lines. Nat. Prod. Rep. 33, 317–347 (2016).

Article  CAS  PubMed  Google Scholar 

Baltz, R. H. Combinatorial biosynthesis of cyclic lipopeptide antibiotics: a model for synthetic biology to accelerate the evolution of secondary metabolite biosynthetic pathways. ACS Synth. Biol. 3, 748–758 (2014).

Article  CAS  PubMed  Google Scholar 

Calcott, M. J., Owen, J. G. & Ackerley, D. F. Efficient rational modification of non-ribosomal peptides by adenylation domain substitution. Nat. Commun. 11, 4554 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fleischhacker, K. et al. De novo design and engineering of non-ribosomal peptide synthetases. Nat. Chem. 10, 275–281 (2018).

Article  PubMed  Google Scholar 

Bozhuyuk, K. A. J. et al. Modification and de novo design of non-ribosomal peptide synthetases using specific assembly points within condensation domains. Nat. Chem. 11, 653–661 (2019).

Article  CAS  PubMed  Google Scholar 

Bozhüyük, K. A. J. et al. Evolution inspired engineering of megasynthetases. Preprint at bioRxiv https://doi.org/10.1101/2022.12.02.518901 (2022).

Kries, H., Niquille, D. L. & Hilvert, D. A subdomain swap strategy for reengineering nonribosomal peptides. Chem. Biol. 22, 640–648 (2015).

Article  CAS  PubMed  Google Scholar 

Thong, W. L. et al. Gene editing enables rapid engineering of complex antibiotic assembly lines. Nat. Commun. 12, 6872 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Baunach, M., Chowdhury, S., Stallforth, P. & Dittmann, E. The landscape of recombination events that create nonribosomal peptide diversity. Mol. Biol. Evol. 38, 2116–2130 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Booth, T. J. et al. Bifurcation drives the evolution of assembly-line biosynthesis. Nat. Commun. 13, 3498 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhong, L. et al. Engineering and elucidation of the lipoinitiation process in nonribosomal peptide biosynthesis. Nat. Commun. 12, 296 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Charlop-Powers, Z. et al. Global biogeographic sampling of bacterial secondary metabolism. eLife 4, e05048 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Charlop-Powers, Z., Owen, J. G., Reddy, B. V. B., Ternei, M. A. & Brady, S. F. Chemical–biogeographic survey of secondary metabolism in soil. Proc. Natl Acad. Sci. USA 111, 3757–3762 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu, R., Li, X. & Lam, K. S. Combinatorial chemistry in drug discovery. Curr. Opin. Chem. Biol. 28, 117–126 (2017).

Article  Google Scholar 

Marahiel, M. A., Stachelhaus, T. & Mootz, H. D. Modular peptide synthetases involved in nonribosomal peptide synthesis. Chem. Rev. 97, 2651–2673 (1997).

Article  CAS  PubMed  Google Scholar 

Baltz, R. H. Natural product drug discovery in the genomic era: realities, conjectures, misconceptions, and opportunities. J. Ind. Microbiol. Biotechnol. 46, 281–299 (2019).

Article  CAS  PubMed  Google Scholar 

Schneider, T. D. & Stephens, R. M. Sequence logos: a new way to display consensus sequences. Nucleic Acids Res. 18, 6097–6100 (1990).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Voigt, C. A., Martinez, C., Wang, Z. G., Mayo, S. L. & Arnold, F. H. Protein building blocks preserved by recombination. Nat. Struct. Biol. 9, 553–558 (2002).

CAS  PubMed  Google Scholar 

Tan, K. M. et al. Structures of teixobactin-producing nonribosomal peptide synthetase condensation and adenylation domains. Curr. Res. Struct. Biol. 2, 14–24 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Wang, Y. et al. ThreaDomEx: a unified platform for predicting continuous and discontinuous protein domains by multiple-threading and segment assembly. Nucleic Acids Res. 45, W400–W407 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Steiniger, C., Hoffmann, S. & Sussmuth, R. D. Desymmetrization of cyclodepsipeptides by assembly mode switching of iterative nonribosomal peptide synthetases. ACS Synth. Biol. 8, 661–667 (2019).

Article  CAS  PubMed  Google Scholar 

Yakimov, M. M., Giuliano, L., Timmis, K. N. & Golyshin, P. N. Recombinant acylheptapeptide lichenysin: high level of production by Bacillus subtilis cells. J. Mol. Microbiol. Biotechnol. 2, 217–224 (2000).

CAS  PubMed  Google Scholar 

Doekel, S. et al. Non-ribosomal peptide synthetase module fusions to produce derivatives of daptomycin in Streptomyces roseosporus. Microbiology (Reading) 154, 2872–2880 (2008).

Article  CAS  PubMed  Google Scholar 

Mootz, H. D., Schwarzer, D. & Marahiel, M. A. Construction of hybrid peptide synthetases by module and domain fusions. Proc. Natl Acad. Sci. USA 97, 5848–5853 (2000).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Linhart, C. & Shamir, R. The degenerate primer design problem: theory and applications. J. Comput. Biol. 12, 431–456 (2005).

Article  CAS  PubMed  Google Scholar 

Hsieh, T. C., Ma, K. H. & Chao, A. iNEXT: an R package for rarefaction and extrapolation of species diversity (Hill numbers). Methods Ecol. Evol. 7, 1451–1456 (2016).

Article  Google Scholar 

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