Non-modular fatty acid synthases yield distinct N-terminal acylation in ribosomal peptides.
Journal
Nature chemistry
ISSN: 1755-4349
Titre abrégé: Nat Chem
Pays: England
ID NLM: 101499734
Informations de publication
Date de publication:
25 Mar 2024
25 Mar 2024
Historique:
received:
24
05
2023
accepted:
27
02
2024
medline:
26
3
2024
pubmed:
26
3
2024
entrez:
26
3
2024
Statut:
aheadofprint
Résumé
Recent efforts in genome mining of ribosomally synthesized and post-translationally modified peptides (RiPPs) have expanded the diversity of post-translational modification chemistries. However, RiPPs are rarely reported as hybrid molecules incorporating biosynthetic machinery from other natural product families. Here we report lipoavitides, a class of RiPP/fatty-acid hybrid lipopeptides that display a unique, putatively membrane-targeting 4-hydroxy-2,4-dimethylpentanoyl (HMP)-modified N terminus. The HMP is formed via condensation of isobutyryl-coenzyme A (isobutyryl-CoA) and methylmalonyl-CoA catalysed by a 3-ketoacyl-(acyl carrier protein) synthase III enzyme, followed by successive tailoring reactions in the fatty acid biosynthetic pathway. The HMP and RiPP substructures are then connected by an acyltransferase exhibiting promiscuous activity towards the fatty acyl and RiPP substrates. Overall, the discovery of lipoavitides contributes a prototype of RiPP/fatty-acid hybrids and provides possible enzymatic tools for lipopeptide bioengineering.
Identifiants
pubmed: 38528101
doi: 10.1038/s41557-024-01491-3
pii: 10.1038/s41557-024-01491-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : AI144967
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : AI144967
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : AI144967
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : AI144967
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : AI144967
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : AI144967
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Arnison, P. G. et al. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat. Prod. Rep. 30, 108–160 (2013).
pubmed: 23165928
pmcid: 3954855
doi: 10.1039/C2NP20085F
Montalban-Lopez, M. et al. New developments in RiPP discovery, enzymology and engineering. Nat. Prod. Rep. 38, 130–239 (2021).
pubmed: 32935693
doi: 10.1039/D0NP00027B
Cao, L., Do, T. & Link, A. J. Mechanisms of action of ribosomally synthesized and posttranslationally modified peptides (RiPPs). J. Ind. Microbiol. Biotechnol. 48, kuab005 (2021).
pubmed: 33928382
pmcid: 8183687
doi: 10.1093/jimb/kuab005
Ongpipattanakul, C. et al. Mechanism of action of ribosomally synthesized and post-translationally modified peptides. Chem. Rev. 122, 14722–14814 (2022).
pubmed: 36049139
pmcid: 9897510
doi: 10.1021/acs.chemrev.2c00210
Melby, J. O., Nard, N. J. & Mitchell, D. A. Thiazole/oxazole-modified microcins: complex natural products from ribosomal templates. Curr. Opin. Chem. Biol. 15, 369–378 (2011).
pubmed: 21429787
pmcid: 3947797
doi: 10.1016/j.cbpa.2011.02.027
Franz, L., Kazmaier, U., Truman, A. W. & Koehnke, J. Bottromycins - biosynthesis, synthesis and activity. Nat. Prod. Rep. 38, 1659–1683 (2021).
pubmed: 33621290
doi: 10.1039/D0NP00097C
Vinogradov, A. A. & Suga, H. Introduction to thiopeptides: biological activity, biosynthesis, and strategies for functional reprogramming. Cell Chem. Biol. 27, 1032–1051 (2020).
pubmed: 32698017
doi: 10.1016/j.chembiol.2020.07.003
McIntosh, J. A., Donia, M. S. & Schmidt, E. W. Insights into heterocyclization from two highly similar enzymes. J. Am. Chem. Soc. 132, 4089–4091 (2010).
pubmed: 20210311
pmcid: 2862276
doi: 10.1021/ja9107116
Burkhart, B. J., Schwalen, C. J., Mann, G., Naismith, J. H. & Mitchell, D. A. YcaO-dependent posttranslational amide activation: biosynthesis, structure, and function. Chem. Rev. 117, 5389–5456 (2017).
pubmed: 28256131
pmcid: 5406272
doi: 10.1021/acs.chemrev.6b00623
Norris, G. E. & Patchett, M. L. The glycocins: in a class of their own. Curr. Opin. Struct. Biol. 40, 112–119 (2016).
pubmed: 27662231
doi: 10.1016/j.sbi.2016.09.003
Saad, H. et al. Nocathioamides, uncovered by a tunable metabologenomic approach, define a novel class of chimeric lanthipeptides. Angew. Chem. Int. Ed. 60, 16472–16479 (2021).
doi: 10.1002/anie.202102571
Medema, M. H., Cimermancic, P., Sali, A., Takano, E. & Fischbach, M. A. A systematic computational analysis of biosynthetic gene cluster evolution: lessons for engineering biosynthesis. PLoS Comput. Biol. 10, e1004016 (2014).
pubmed: 25474254
pmcid: 4256081
doi: 10.1371/journal.pcbi.1004016
Robey, M. T., Caesar, L. K., Drott, M. T., Keller, N. P. & Kelleher, N. L. An interpreted atlas of biosynthetic gene clusters from 1,000 fungal genomes. Proc. Natl Acad. Sci. USA 118, e2020230118 (2021).
pubmed: 33941694
pmcid: 8126772
doi: 10.1073/pnas.2020230118
Gavriilidou, A. et al. Compendium of specialized metabolite biosynthetic diversity encoded in bacterial genomes. Nat. Microbiol. 7, 726–735 (2022).
pubmed: 35505244
doi: 10.1038/s41564-022-01110-2
Walsh, C. T., Brien, R. V. O. & Khosla, C. Nonproteinogenic amino acid building blocks for nonribosomal peptide and hybrid polyketide scaffolds. Angew. Chem. Int. Ed. 52, 7098–7124 (2013).
doi: 10.1002/anie.201208344
Just-Baringo, X., Albericio, F. & Alvarez, M. Thiopeptide antibiotics: retrospective and recent advances. Mar. Drugs 12, 317–351 (2014).
pubmed: 24445304
pmcid: 3917276
doi: 10.3390/md12010317
Noike, M. et al. A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin. Nat. Chem. Biol. 11, 71–76 (2015).
pubmed: 25402768
doi: 10.1038/nchembio.1697
Ortiz-Lopez, F. J. et al. Cacaoidin, first member of the new lanthidin RiPP family. Angew. Chem. Int. Ed. 59, 12654–12658 (2020).
doi: 10.1002/anie.202005187
Jordan, P. A. & Moore, B. S. Biosynthetic pathway connects cryptic ribosomally synthesized posttranslationally modified peptide genes with pyrroloquinoline alkaloids. Cell Chem. Biol. 23, 1504–1514 (2016).
pubmed: 27866908
pmcid: 5182094
doi: 10.1016/j.chembiol.2016.10.009
Wiebach, V. et al. The anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptides. Nat. Chem. Biol. 14, 652–654 (2018).
pubmed: 29915235
doi: 10.1038/s41589-018-0068-6
Wiebach, V. et al. An amphipathic alpha-helix guides maturation of the ribosomally-synthesized lipolanthines. Angew. Chem. Int. Ed. 59, 16777–16785 (2020).
doi: 10.1002/anie.202003804
Kozakai, R. et al. Acyltransferase that catalyses the condensation of polyketide and peptide moieties of goadvionin hybrid lipopeptides. Nat. Chem. 12, 869–877 (2020).
pubmed: 32719482
doi: 10.1038/s41557-020-0508-2
Doroghazi, J. R. et al. A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nat. Chem. Biol. 10, 963–968 (2014).
pubmed: 25262415
pmcid: 4201863
doi: 10.1038/nchembio.1659
Blin, K. et al. AntiSMASH 6.0: improving cluster detection and comparison capabilities. Nucleic Acids Res. 49, W29–W35 (2021).
pubmed: 33978755
pmcid: 8262755
doi: 10.1093/nar/gkab335
Grant-Mackie, E. S., Williams, E. T., Harris, P. W. R. & Brimble, M. A. Aminovinyl cysteine containing peptides: a unique motif that imparts key biological activity. JACS Au 1, 1527–1540 (2021).
pubmed: 34723257
pmcid: 8549060
doi: 10.1021/jacsau.1c00308
Eyles, T. H., Vior, N. M., Lacret, R. & Truman, A. W. Understanding thioamitide biosynthesis using pathway engineering and untargeted metabolomics. Chem. Sci. 12, 7138–7150 (2021).
pubmed: 34123341
pmcid: 8153245
doi: 10.1039/D0SC06835G
Xu, M. et al. Functional genome mining reveals a class V lanthipeptide containing a D-amino acid introduced by an F
doi: 10.1002/anie.202008035
Kloosterman, A. M. et al. Expansion of RiPP biosynthetic space through integration of pan-genomics and machine learning uncovers a novel class of lantibiotics. PLoS Biol. 18, e3001026 (2020).
pubmed: 33351797
pmcid: 7794033
doi: 10.1371/journal.pbio.3001026
Schujman, G. E. & de Mendoza, D. Regulation of type II fatty acid synthase in Gram-positive bacteria. Curr. Opin. Microbiol. 11, 148–152 (2008).
pubmed: 18372209
doi: 10.1016/j.mib.2008.02.002
Hu, L. et al. Characterization of histidine functionalization and its timing in the biosynthesis of ribosomally synthesized and posttranslationally modified thioamitides. J. Am. Chem. Soc. 144, 4431–4438 (2022).
pubmed: 35230829
doi: 10.1021/jacs.1c11669
Sikandar, A., Lopatniuk, M., Luzhetskyy, A., Muller, R. & Koehnke, J. Total in vitro biosynthesis of the thioamitide thioholgamide and investigation of the pathway. J. Am. Chem. Soc. 144, 5136–5144 (2022).
pubmed: 35263083
doi: 10.1021/jacs.2c00402
Enghiad, B. et al. Cas12a-assisted precise targeted cloning using in vivo Cre-lox recombination. Nat. Commun. 12, 1171 (2021).
pubmed: 33608525
pmcid: 7896053
doi: 10.1038/s41467-021-21275-4
Frattaruolo, L., Lacret, R., Cappello, A. R. & Truman, A. W. A genomics-based approach identifies a thioviridamide-like compound with selective anticancer activity. ACS Chem. Biol. 12, 2815–2822 (2017).
pubmed: 28968491
doi: 10.1021/acschembio.7b00677
Bhushan, R. & Bruckner, H. Use of Marfey’s reagent and analogs for chiral amino acid analysis: assessment and applications to natural products and biological systems. J. Chromatogr. B 879, 3148–3161 (2011).
doi: 10.1016/j.jchromb.2011.05.058
Nilsson, J. et al. Enrichment of glycopeptides for glycan structure and attachment site identification. Nat. Methods 6, 809–811 (2009).
pubmed: 19838169
doi: 10.1038/nmeth.1392
Gabrielson, S. SciFinder. J. Med. Libr. Assoc. 106, 588–590 (2018).
pmcid: 6148602
doi: 10.5195/jmla.2018.515
Bender, C. L., Alarcon-Chaidez, F. & Gross, D. C. Pseudomonas syringae phytotoxins: mode of action, regulation, and biosynthesis by peptide and polyketide synthetases. Microbiol. Mol. Biol. Rev. 63, 266–292 (1999).
pubmed: 10357851
pmcid: 98966
doi: 10.1128/MMBR.63.2.266-292.1999
Fu, J. et al. Full-length RecE enhances linear-linear homologous recombination and facilitates direct cloning for bioprospecting. Nat. Biotechnol. 30, 440–446 (2012).
pubmed: 22544021
doi: 10.1038/nbt.2183
Tang, L., Zhang, Y. X. & Hutchinson, C. R. Amino acid catabolism and antibiotic synthesis: valine is a source of precursors for macrolide biosynthesis in Streptomyces ambofaciens and Streptomyces fradiae. J. Bacteriol. 176, 6107–6119 (1994).
pubmed: 7928973
pmcid: 196831
doi: 10.1128/jb.176.19.6107-6119.1994
Dayem, L. C. et al. Metabolic engineering of a methylmalonyl-CoA mutase–epimerase pathway for complex polyketide biosynthesis in Escherichia coli. Biochemistry 41, 5193–5201 (2002).
pubmed: 11955068
doi: 10.1021/bi015593k
Okamura, E., Tomita, T., Sawa, R., Nishiyama, M. & Kuzuyama, T. Unprecedented acetoacetyl-coenzyme A synthesizing enzyme of the thiolase superfamily involved in the mevalonate pathway. Proc. Natl Acad. Sci. USA 107, 11265–11270 (2010).
pubmed: 20534558
pmcid: 2895072
doi: 10.1073/pnas.1000532107
Inahashi, Y. et al. Biosynthesis of trehangelin in Polymorphospora rubra K07-0510: identification of metabolic pathway to angelyl-CoA. ChemBioChem 17, 1442–1447 (2016).
pubmed: 27311629
doi: 10.1002/cbic.201600208
Bobik, T. A. & Rasche, M. E. Identification of the human methylmalonyl-CoA racemase gene based on the analysis of prokaryotic gene arrangements. Implications for decoding the human genome. J. Biol. Chem. 276, 37194–37198 (2001).
pubmed: 11481338
doi: 10.1074/jbc.M107232200
Peter, D. M., Vogeli, B., Cortina, N. S. & Erb, T. J. A chemo-enzymatic road map to the synthesis of CoA esters. Molecules 21, 517 (2016).
pubmed: 27104508
pmcid: 6273144
doi: 10.3390/molecules21040517
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
pubmed: 34265844
pmcid: 8371605
doi: 10.1038/s41586-021-03819-2
Morris, G. M., Goodsell, D. S., Huey, R. & Olson, A. J. Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4. J. Comput. Aided Mol. Des. 10, 293–304 (1996).
pubmed: 8877701
doi: 10.1007/BF00124499
Kuhn, M. L., Majorek, K. A., Minor, W. & Anderson, W. F. Broad-substrate screen as a tool to identify substrates for bacterial Gcn5-related N-acetyltransferases with unknown substrate specificity. Protein Sci. 22, 222–230 (2013).
pubmed: 23184347
doi: 10.1002/pro.2199
Ramesh, S. et al. Bioinformatics-guided expansion and discovery of graspetides. ACS Chem. Biol. 16, 2787–2797 (2021).
pubmed: 34766760
pmcid: 8688276
doi: 10.1021/acschembio.1c00672
Imai, Y. et al. A new antibiotic selectively kills Gram-negative pathogens. Nature 576, 459–464 (2019).
pubmed: 31747680
pmcid: 7188312
doi: 10.1038/s41586-019-1791-1
Park, H. B., Perez, C. E., Barber, K. W., Rinehart, J. & Crawford, J. M. Genome mining unearths a hybrid nonribosomal peptide synthetase-like-pteridine synthase biosynthetic gene cluster. eLife 6, e25229 (2017).
pubmed: 28431213
pmcid: 5384830
doi: 10.7554/eLife.25229
Schor, R., Schotte, C., Wibberg, D., Kalinowski, J. & Cox, R. J. Three previously unrecognised classes of biosynthetic enzymes revealed during the production of xenovulene A. Nat. Commun. 9, 1963 (2018).
pubmed: 29773797
pmcid: 5958101
doi: 10.1038/s41467-018-04364-9
Yee, D. A. et al. Genome mining of alkaloidal terpenoids from a hybrid terpene and nonribosomal peptide biosynthetic pathway. J. Am. Chem. Soc. 142, 710–714 (2020).
pubmed: 31885262
pmcid: 7000236
doi: 10.1021/jacs.9b13046
Gotze, S. & Stallforth, P. Structure elucidation of bacterial nonribosomal lipopeptides. Org. Biomol. Chem. 18, 1710–1727 (2020).
pubmed: 32052002
doi: 10.1039/C9OB02539A
Robbel, L. & Marahiel, M. A. Daptomycin, a bacterial lipopeptide synthesized by a nonribosomal machinery. J. Biol. Chem. 285, 27501–27508 (2010).
pubmed: 20522545
pmcid: 2934615
doi: 10.1074/jbc.R110.128181
Poirel, L., Jayol, A. & Nordmann, P. Polymyxins: antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin. Microbiol. Rev. 30, 557–596 (2017).
pubmed: 28275006
pmcid: 5355641
doi: 10.1128/CMR.00064-16
Huttel, W. Echinocandins: structural diversity, biosynthesis, and development of antimycotics. Appl. Microbiol. Biotechnol. 105, 55–66 (2021).
pubmed: 33270153
doi: 10.1007/s00253-020-11022-y
Hubrich, F. et al. Ribosomally derived lipopeptides containing distinct fatty acyl moieties. Proc. Natl Acad. Sci. USA 119, e2113120119 (2022).
pubmed: 35027450
pmcid: 8784127
doi: 10.1073/pnas.2113120119
Pickens, L. B. et al. Biochemical analysis of the biosynthetic pathway of an anticancer tetracycline SF2575. J. Am. Chem. Soc. 131, 17677–17689 (2009).
pubmed: 19908837
pmcid: 2800175
doi: 10.1021/ja907852c
Ozaki, T. et al. Dissection of goadsporin biosynthesis by in vitro reconstitution leading to designer analogues expressed in vivo. Nat. Commun. 8, 14207 (2017).
pubmed: 28165449
pmcid: 5303826
doi: 10.1038/ncomms14207
Zong, C., Cheung-Lee, W. L., Elashal, H. E., Raj, M. & Link, A. J. Albusnodin: an acetylated lasso peptide from Streptomyces albus. Chem. Commun. 54, 1339–1342 (2018).
doi: 10.1039/C7CC08620B
Ziemert, N., Ishida, K., Liaimer, A., Hertweck, C. & Dittmann, E. Ribosomal synthesis of tricyclic depsipeptides in bloom-forming cyanobacteria. Angew. Chem. Int. Ed. 47, 7756–7759 (2008).
doi: 10.1002/anie.200802730
Kieser, T., Bibb, M.J., Buttner, M.J., Chater, K.F. & Hopwood, D.A. Practical Streptomyces Genetics (John Innes Foundation, 2000).
Tamura, K., Stecher, G. & Kumar, S. MEGA11: molecular evolutionary genetics analysis version 11. Mol. Biol. Evol. 38, 3022–3027 (2021).
pubmed: 33892491
pmcid: 8233496
doi: 10.1093/molbev/msab120
Stewart, J. J. P. MOPAC2016 (Stewart Computational Chemistry, 2016).
Krieger, E. & Vriend, G. YASARA View—molecular graphics for all devices—from smartphones to workstations. Bioinformatics 30, 2981–2982 (2014).
pubmed: 24996895
pmcid: 4184264
doi: 10.1093/bioinformatics/btu426
Trott, O. & Olson, A. J. Software news and update AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455–461 (2010).
pubmed: 19499576
pmcid: 3041641
doi: 10.1002/jcc.21334
Wang, J. M., Cieplak, P. & Kollman, P. A. How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J. Comput. Chem. 21, 1049–1074 (2000).
doi: 10.1002/1096-987X(200009)21:12<1049::AID-JCC3>3.0.CO;2-F
Duan, Y. et al. A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J. Comput. Chem. 24, 1999–2012 (2003).
pubmed: 14531054
doi: 10.1002/jcc.10349
Wang, J. M., Wolf, R. M., Caldwell, J. W., Kollman, P. A. & Case, D. A. Development and testing of a general amber force field. J. Comput. Chem. 25, 1157–1174 (2004).
pubmed: 15116359
doi: 10.1002/jcc.20035
Jakalian, A., Jack, D. B. & Bayly, C. I. Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation. J. Comput. Chem. 23, 1623–1641 (2002).
pubmed: 12395429
doi: 10.1002/jcc.10128
Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).
pubmed: 32881101
doi: 10.1002/pro.3943
Jurcik, A. et al. CAVER Analyst 2.0: analysis and visualization of channels and tunnels in protein structures and molecular dynamics trajectories. Bioinformatics 34, 3586–3588 (2018).
pubmed: 29741570
pmcid: 6184705
doi: 10.1093/bioinformatics/bty386