{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:56:25Z","timestamp":1777488985366,"version":"3.51.4"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"6797","license":[{"start":{"date-parts":[[2000,8,17]],"date-time":"2000-08-17T00:00:00Z","timestamp":966470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2000,8,17]],"date-time":"2000-08-17T00:00:00Z","timestamp":966470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2000,8,17]]},"DOI":"10.1038\/35021219","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T08:45:49Z","timestamp":1027673149000},"page":"775-781","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1235,"title":["Molecular mechanisms that confer antibacterial drug resistance"],"prefix":"10.1038","volume":"406","author":[{"given":"Christopher","family":"Walsh","sequence":"first","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2000,8,17]]},"reference":[{"key":"BF35021219_CR1","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1126\/science.257.5073.1064","volume":"257","author":"HC Neu","year":"1992","unstructured":"Neu, H.C. The crisis in antibiotic resistance. Science 257, 1064\u20131073 (1992).","journal-title":"Science"},{"key":"BF35021219_CR2","first-page":"144","volume":"335","author":"HS Gold","year":"1996","unstructured":"Gold, H. S. & Moellering, R.C. Antimicrobial-drug resistance . N. Engl. J. Med. 335, 144\u2013 1453 (1996).","journal-title":"N. Engl. J. Med."},{"key":"BF35021219_CR3","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/scientificamerican0398-46","volume":"275","author":"SB Levy","year":"1998","unstructured":"Levy, S.B. The challenge of antibiotic resistance. Sci. Am. 275 , 46\u201353 (1998).","journal-title":"Sci. Am."},{"key":"BF35021219_CR4","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1056\/NEJM199805073381909","volume":"338","author":"SB Levy","year":"1998","unstructured":"Levy, S.B. Multidrug resistance\u2014a sign of the times. N. Engl. J. Med.  338, 1376\u20131378 ( 1998).","journal-title":"N. Engl. J. Med."},{"key":"BF35021219_CR5","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1093\/clinids\/10.4.699","volume":"10","author":"BG Spratt","year":"1988","unstructured":"Spratt, B. G. & Cromie, K. D. Rev. Infect. Dis.  10, 699 (1988).","journal-title":"Rev. Infect. Dis."},{"key":"BF35021219_CR6","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1039\/NP9961300469","volume":"13","author":"DH Williams","year":"1996","unstructured":"Williams, D.H. The glycopeptide story\u2014how to kill the deadly \u201csuperbugs\u201d . Nat. Prod. Rep. 13, 469\u2013 477 (1996).","journal-title":"Nat. Prod. Rep."},{"issue":"Suppl. B","key":"BF35021219_CR7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/jac\/22.Supplement_B.13","volume":"22","author":"A Brisson-Noel","year":"1988","unstructured":"Brisson-Noel, A., Trieu-Cuot, P. & Courvalin, P. Mechanism of action of spiramycin and other macrolides . J. Antimicrob. Chemother. 22(Suppl. B), 13\u201323 (1988).","journal-title":"J. Antimicrob. Chemother."},{"key":"BF35021219_CR8","first-page":"317","volume-title":"The Tetracyclines, Handbook of Experimental Pharmacology","author":"I Chopra","year":"1985","unstructured":"Chopra, I. in The Tetracyclines, Handbook of Experimental Pharmacology Vol 78  (eds Hlavaka, J. J. & Boothe, J. H.) 317\u2013 392 (Springer, Berlin, 1985)."},{"key":"BF35021219_CR9","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1126\/science.274.5291.1367","volume":"274","author":"D Fourmy","year":"1996","unstructured":"Fourmy, D., Recht, M. I., Blanchard, S. C. & Puglisi, J.D. Structure of the A site of the Escherichia coli 16S ribosomal RNA complexed with an aminoglycoside antibiotic. Science 274, 1371\u20131376 (1996).","journal-title":"Science"},{"key":"BF35021219_CR10","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1006\/jmbi.1999.3247","volume":"294","author":"P Kloss","year":"1999","unstructured":"Kloss, P., Xiong, L., Shinabarger, D. L. & Mankin, A.S. Resistance of mutations in 23S rRNA identify the site of action of the protein synthesis inhibitor linezolid in the ribosomal peptidyl transferase center . J. Mol. Biol. 294, 93\u2013 101 (1999).","journal-title":"J. Mol. Biol."},{"key":"BF35021219_CR11","volume-title":"Quinolone Antibacterial Agents","author":"LL Shen","year":"1993","unstructured":"Shen, L.L. in Quinolone Antibacterial Agents, 2nd edn (eds Hooper, D. C. & Wolfson, J. S.) 77 (American Society for Microbiology, Washington DC, 1993)."},{"key":"BF35021219_CR12","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/S0966-842X(96)10085-8","volume":"5","author":"A Maxwell","year":"1997","unstructured":"Maxwell, A. DNA gyrase as a drug target. Trends Microbiol. 5, 102\u2013109 (1997).","journal-title":"Trends Microbiol."},{"key":"BF35021219_CR13","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1128\/AAC.39.7.1554","volume":"39","author":"L Ferrero","year":"1995","unstructured":"Ferrero, L., Cameron, B. & Crouzet, J. Analysis of gyrA and grlA mutations in stepwise-selected ciprofloxacin-resistant mutant of Staphylococcus aureus . Antimicrob. Agents Chemother. 39, 1554\u20131558 (1995).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BF35021219_CR14","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/383219a0","volume":"383","author":"J Davies","year":"1996","unstructured":"Davies, J. Bacteria on the rampage. Nature 383, 219 \u2013220 (1996).","journal-title":"Nature"},{"key":"BF35021219_CR15","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/S0002-9343(99)80270-8","volume":"102","author":"E Murray","year":"1997","unstructured":"Murray, E. Vancomycin resistant enterococci. Am. J. Med. 102, 284\u2013293 (1997).","journal-title":"Am. J. Med."},{"key":"BF35021219_CR16","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1128\/AAC.37.8.1563","volume":"37","author":"M Arthur","year":"1993","unstructured":"Arthur, M. & Courvalin, P. Genetics and mechanisms of glycopeptide resistance in enterococci. Antimicrob. Agents Chemother.  37, 1563\u20131571 (1993).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BF35021219_CR17","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S1074-5521(96)90079-4","volume":"3","author":"C Walsh","year":"1996","unstructured":"Walsh, C, Fisher, S. L., Park, I. S., Prahalad, M. & Wu, Z. Bacterial resistance to vancomycin: five genes and one missing hydrogen bond tell the story. Chem. Biol.  3, 21\u201328 (1996 ).","journal-title":"Chem. Biol."},{"key":"BF35021219_CR18","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1126\/science.8153624","volume":"264","author":"J Davies","year":"1994","unstructured":"Davies, J. Inactivation of antibiotics and the dissemination of resistance genes. Science 264, 375\u2013382 ( 1994).","journal-title":"Science"},{"key":"BF35021219_CR19","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1086\/520287","volume":"26","author":"JJ Schentag","year":"1998","unstructured":"Schentag, J.J. et al. Genesis of methicillin resistant Staphylococcus aureus  (MRSA). Clin. Infect. Dis. 26, 1204 \u20131212 (1998).","journal-title":"Clin. Infect. Dis."},{"key":"BF35021219_CR20","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1056\/NEJM199102283240906","volume":"324","author":"GA Jacoby","year":"1991","unstructured":"Jacoby, G. A. & Archer, G.L. New mechanisms of resistance to antibacterial agents. N. Engl. J. Med. 324, 601\u2013612 (1991).","journal-title":"N. Engl. J. Med."},{"key":"BF35021219_CR21","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1128\/AAC.36.4.695","volume":"36","author":"SB Levy","year":"1992","unstructured":"Levy, S.B. Active efflux mechanisms for antimicrobial resistance. Antimicrob. Agents Chemother. 36, 695\u2013703 (1992).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BF35021219_CR22","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1128\/mr.60.4.575-608.1996","volume":"60","author":"IT Paulsen","year":"1996","unstructured":"Paulsen, I. T., Brown, M. H. & Skurray, R.A. Proton-dependent multidrug efflux systems. Microbiol. Rev. 60, 575\u2013608 (1996).","journal-title":"Microbiol. Rev."},{"key":"BF35021219_CR23","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1111\/j.1365-2958.1990.tb00696.x","volume":"4","author":"J Ross","year":"1990","unstructured":"Ross, J. et al. Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super gene family. Mol. Microbiol. 4, 1207\u20131214 (1990).","journal-title":"Mol. Microbiol."},{"key":"BF35021219_CR24","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1128\/AAC.28.2.302","volume":"28","author":"A Philippon","year":"1985","unstructured":"Philippon, A., Labia, R. & Jacoby, G. Extended spectrum beta-lactamases. Antimicrob. Agents Chemother. 28, 302\u2013307 (1985).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BF35021219_CR25","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1128\/mr.57.1.138-163.1993","volume":"57","author":"KJ Shaw","year":"1993","unstructured":"Shaw, K. J., Rather, P. N., Hare, S. R. & Miller, G. H. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol. Rev.  57, 138\u2013163 (1993).","journal-title":"Microbiol. Rev."},{"key":"BF35021219_CR26","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/S0092-8674(00)80274-3","volume":"89","author":"WC Hon","year":"1997","unstructured":"Hon, W. C. et al. Structure of an enzyme required for aminoglycoside antibiotic resistance reveals homology to eukaryotic protein kinases. Cell  89, 887\u2013895 ( 1997).","journal-title":"Cell"},{"key":"BF35021219_CR27","doi-asserted-by":"publisher","first-page":"7103","DOI":"10.1021\/bi973113c","volume":"37","author":"D Bussiere","year":"1998","unstructured":"Bussiere, D. et al. Crystal structure of ErmC\u2032, an rRNA methyltransferase which mediates antibiotic resistance in bacteria. Biochemistry  37, 7103\u20137112 ( 1998).","journal-title":"Biochemistry"},{"key":"BF35021219_CR28","doi-asserted-by":"publisher","first-page":"10408","DOI":"10.1021\/bi00107a007","volume":"30","author":"TDH Bugg","year":"1991","unstructured":"Bugg, T. D. H. et al. Molecular basis for vancomycin resistance in Enterococcus faecium, BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. Biochemistry  30, 10408\u201310415 (1991).","journal-title":"Biochemistry"},{"key":"BF35021219_CR29","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/0014-5793(87)80373-3","volume":"221","author":"MD Song","year":"1987","unstructured":"Song, M. D., Wachi, M., Doi, M., Ishino, F. & Matsuhashi, M. Evolution of an inducible penicillin target protein in MRSA by gene fusion. FEBS Lett. 221, 167 (1987).","journal-title":"FEBS Lett."},{"key":"BF35021219_CR30","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1126\/science.8153626","volume":"264","author":"BG Spratt","year":"1994","unstructured":"Spratt, B. G. Resistance to antibiotics mediated by target alterations. Science  264, 388\u2013393 ( 1994).","journal-title":"Science"},{"key":"BF35021219_CR31","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1021\/ar00112a001","volume":"18","author":"JR Knowles","year":"1985","unstructured":"Knowles, J. R. Penicillin resistance: the chemistry of beta-lactamase inhibition. Acc. Chem. Res. 18, 97\u2013105 (1985).","journal-title":"Acc. Chem. Res."},{"key":"BF35021219_CR32","doi-asserted-by":"crossref","unstructured":"The choice of antibacterial drugs. Med. Lett. 41, 95\u2013104 ( 1999).","DOI":"10.1023\/A:1018889825562"},{"key":"BF35021219_CR33","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1021\/jm00035a016","volume":"37","author":"ML Nelson","year":"1994","unstructured":"Nelson, M. L., Park, B. H. & Levy, S. B. Molecular requirement for the inhibition of the tetracycline antiport protein and the effect of potent inhibitors on the growth of tetracycline-resistant bacteria. J. Med. Chem. 37, 1355\u2013 1361 (1994).","journal-title":"J. Med. Chem."},{"key":"BF35021219_CR34","doi-asserted-by":"publisher","first-page":"3853","DOI":"10.1021\/jm960294s","volume":"39","author":"DW Chu","year":"1996","unstructured":"Chu, D. W., Plattner, J. J. & Katz, L. New directions in antibacterial research. J. Med. Chem. 39, 3853\u20133874 (1996).","journal-title":"J. Med. Chem."},{"key":"BF35021219_CR35","unstructured":"Agouridas, C., Benedetti, Y., Denis, A., Le Martert, O. & Chantot, J. F. Ketolides: a new distinct class of macrolide antibacterials, synthesis and structural characteristics of RU 004. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy Abstr. F158 (American Society for Microbiology, 1995)."},{"key":"BF35021219_CR36","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.1128\/AAC.41.10.2165","volume":"41","author":"F Biavasco","year":"1997","unstructured":"Biavasco, F. et al. In vitro antibacterial activity of LY333328, a new semisynthetic glycopeptide. Antimicrob. Agents Chemother. 41, 2165\u20132172 (1997).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BF35021219_CR37","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1126\/science.280.5364.711","volume":"280","author":"DH Williams","year":"1998","unstructured":"Williams, D. H., Maguire, A. J., Tsuzuki, W. & Westwell, M. S. An analysis of the origins of cooperative binding energy of dimerization. Science 280, 711\u2013713 ( 1998).","journal-title":"Science"},{"key":"BF35021219_CR38","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1126\/science.284.5413.507","volume":"284","author":"M Ge","year":"1999","unstructured":"Ge, M. et al. Vancomycin derivatives that inhibit peptidoglycan biosynthesis without binding D-Ala-D-Ala. Science 284, 507\u2013511 (1999).","journal-title":"Science"},{"key":"BF35021219_CR39","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1126\/science.284.5413.442","volume":"284","author":"C Walsh","year":"1999","unstructured":"Walsh, C. Deconstructing vancomycin. Science 284, 442\u2013443 (1999).","journal-title":"Science"},{"key":"BF35021219_CR40","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1128\/AAC.39.1.238","volume":"39","author":"AL Barry","year":"1995","unstructured":"Barry, A. L. & Fuchs, P. C. In vitro activities of a streptogramin (RP59500), three macrolides, and an azolide against four respiratory tract pathogens. Agents Chemother. 39, 238\u2013 240 (1995).","journal-title":"Agents Chemother."},{"issue":"Suppl. A","key":"BF35021219_CR41","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1093\/jac\/39.suppl_1.145","volume":"39","author":"PK Linden","year":"1997","unstructured":"Linden, P. K., Pasculle, A. W., McDevitt, D. & Kramer, D. J. Effect of quinupristin\/dalfopristin (synercid) treatment of infections caused by vancomycin-resistant Enterococcus faecium (VREF). J. Antimicrob. Chemother. 39(Suppl. A), 145 \u2013151 (1997).","journal-title":"J. Antimicrob. Chemother."},{"key":"BF35021219_CR42","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1086\/313597","volume":"30","author":"JW Chien","year":"2000","unstructured":"Chien, J. W., Kucia, M. L. & Salata, R. A. Use of linezolid, an oxazolidinone, in the treatment of multidrug-resistant gram-positive bacterial infections. Clin. Infect. Dis. 30, 146\u2013151 (2000).","journal-title":"Clin. Infect. Dis."},{"key":"BF35021219_CR43","doi-asserted-by":"publisher","first-page":"12570","DOI":"10.1021\/bi961017q","volume":"35","author":"M Kurz","year":"1996","unstructured":"Kurz, M. & Guba, W. 3D structure of ramoplanin: a potent inhibitor of bacterial cell wall biosynthesis. Biochemistry  35, 12570\u201312575 (1996).","journal-title":"Biochemistry"},{"key":"BF35021219_CR44","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1128\/AAC.41.3.497","volume":"41","author":"I Chapra","year":"1997","unstructured":"Chapra, I., Hodgson, J., Metcalf, B. & Poste, G. The search for antimicrobial agents effective against bacteria resistant to multiple antibiotics. Antimicrob. Agents Chemother. 41, 497\u2013 503 (1997).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BF35021219_CR45","doi-asserted-by":"publisher","first-page":"13904","DOI":"10.1021\/bi9711543","volume":"36","author":"MK Chan","year":"1997","unstructured":"Chan, M. K. et al. Crystal structure of E. coli peptide deformylase. Biochemistry 36, 13904\u201313909 (1997).","journal-title":"Biochemistry"},{"key":"BF35021219_CR46","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1021\/bi992245y","volume":"39","author":"DZ Chen","year":"2000","unstructured":"Chen, D. Z. et al. Actinonin, a naturally occurring antibacterial agent is a potent peptide deformylase inhibitor. Biochemistry  39, 1256\u20131262 (2000).","journal-title":"Biochemistry"},{"key":"BF35021219_CR47","first-page":"111","volume":"30","author":"JF Barret","year":"1995","unstructured":"Barret, J. F. & Isaacson, R. E. Bacterial virulence as a potential target for therapeutic intervention. Annu. Rep. Med. Chem.  30, 111\u2013118 (1995).","journal-title":"Annu. Rep. Med. Chem."},{"key":"BF35021219_CR48","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/S1074-5521(97)90217-9","volume":"4","author":"C Stephens","year":"1997","unstructured":"Stephens, C. & Shapiro, L. Bacterial protein secretion\u2014a target for new antibiotics? Chem. Biol. 4, 637\u2013641 (1997).","journal-title":"Chem. Biol."},{"key":"BF35021219_CR49","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1128\/AAC.42.7.1529","volume":"42","author":"JF Barret","year":"1998","unstructured":"Barret, J. F. & Hoch, J. A. Two-component signal transduction as a target for microbial anti-infective therapy. Antimicrob. Agents Chemother. 42, 1529\u20131536 (1998).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BF35021219_CR50","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1046\/j.1365-2958.1997.4251782.x","volume":"24","author":"M Kleerebezem","year":"1997","unstructured":"Kleerebezem, M., Quadri, L. E. N., Kuipers, O. P. & de Vos, W. M. Quorum sensing by peptide pheromones and two-component signal-transduction systems in gram-positive bacteria. Mol. Microbiol.  24, 895\u2013904 (1997).","journal-title":"Mol. Microbiol."},{"key":"BF35021219_CR51","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1046\/j.1365-2958.1997.3291701.x","volume":"24","author":"C Reimmann","year":"1997","unstructured":"Reimmann, C. et al. The global activator gacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. Mol. Microbiol. 24, 309\u2013 319 (1997).","journal-title":"Mol. Microbiol."},{"key":"BF35021219_CR52","doi-asserted-by":"publisher","first-page":"8194","DOI":"10.1021\/jm990212a","volume":"42","author":"MJ Sofia","year":"1999","unstructured":"Sofia, M. J. et al. Discovery of novel disaccharide antibacterial agents using a combinatorial library approach. J. Med. Chem. 42, 8194\u20138198 (1999).","journal-title":"J. Med. Chem."},{"key":"BF35021219_CR53","doi-asserted-by":"publisher","first-page":"8565","DOI":"10.1021\/ja981746o","volume":"120","author":"DS Tan","year":"1998","unstructured":"Tan, D. S., Foley, M. A., Shair, M. D. & Schreiber, S. L. Stereoselective synthesis of over two million compounds having structural features both reminiscent of natural products and compatible with miniaturized cell-based assays. J. Am. Chem. Soc. 120, 8565\u20138566 (1998).","journal-title":"J. Am. Chem. Soc."},{"key":"BF35021219_CR54","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1367-5931(97)80005-1","volume":"1","author":"PF Leadlay","year":"1997","unstructured":"Leadlay, P. F. Combinatorial approaches to polyketide biosynthesis. Curr. Opin. Chem. Biol. 1, 162\u2013168 ( 1997).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"BF35021219_CR55","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1021\/cr960025+","volume":"97","author":"L Katz","year":"1997","unstructured":"Katz, L. Manipulation of modular polyketide synthases. Chem. Rev.  97, 2557\u20132575 (1997).","journal-title":"Chem. Rev."},{"key":"BF35021219_CR56","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.1021\/cr960027u","volume":"97","author":"C Khosla","year":"1997","unstructured":"Khosla, C. Harnessing the biosynthetic potential of modular polyketide synthases. Chem. Rev. 97, 2577\u20132590 (1997).","journal-title":"Chem. Rev."},{"key":"BF35021219_CR57","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1126\/science.282.5386.63","volume":"282","author":"DE Cane","year":"1998","unstructured":"Cane, D. E., Walsh, C. T. & Khosla, C. Harnessing the biosynthetic code: combinations, permutations, and mutations. Science 282, 63\u2013 68 (1998).","journal-title":"Science"},{"key":"BF35021219_CR58","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1073\/pnas.96.5.1846","volume":"96","author":"R McDaniel","year":"1999","unstructured":"McDaniel, R. et al. Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel \"unnatural\" natural products. Proc. Natl Acad. Sci. USA 96, 1846\u2013 1851 (1999).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BF35021219_CR59","doi-asserted-by":"publisher","first-page":"9881","DOI":"10.1021\/ja992810k","volume":"121","author":"L Zhao","year":"1999","unstructured":"Zhao, L. et al. Engineering a methymycin\/pikromycin-calicheamicin hybrid: construction of two new macrolides carrying a designed sugar moiety. J. Am. Chem. Soc. 121, 9881\u20139882 (1999).","journal-title":"J. Am. Chem. Soc."},{"key":"BF35021219_CR60","first-page":"583","volume":"25","author":"DM Schlaes","year":"1997","unstructured":"Schlaes, D.M. et al. Guidelines for the prevention of antimicrobial resistance in hospitals. Clin. Infect. Dis. 25, 583 \u2013599 (1997).","journal-title":"Clin. Infect. Dis."},{"key":"BF35021219_CR61","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1056\/NEJM199902183400709","volume":"340","author":"FA Waldvogel","year":"1999","unstructured":"Waldvogel, F. A. New resistance in Staphylococcus aureus. N. Engl. J. Med.  340, 556\u2013557 ( 1999).","journal-title":"N. Engl. J. Med."},{"key":"BF35021219_CR62","doi-asserted-by":"crossref","unstructured":"Drugs for HIV infection. Med. Lett.  42, 1\u20136 (2000 ).","DOI":"10.1046\/j.1365-2516.2000.00050.x"},{"key":"BF35021219_CR63","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1126\/science.279.5353.996","volume":"279","author":"W Witte","year":"1998","unstructured":"Witte, W. Medical consequences of antibiotic use in agriculture. Science  279, 996\u2013997 ( 1998).","journal-title":"Science"},{"key":"BF35021219_CR64","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1093\/clinids\/24.1.90","volume":"24","author":"JW Chow","year":"1997","unstructured":"Chow, J. W., Donahedian, S. M. & Zervos, M. J. Emergence of increased resistance to quinupristin\/dalfopristin during therapy for Enterococcus faecium bacteremia. Clin. Infect. Dis. 24, 90\u201391 ( 1997).","journal-title":"Clin. Infect. Dis."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/35021219.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/35021219","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/35021219.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T10:07:10Z","timestamp":1663582030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/35021219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,8,17]]},"references-count":64,"journal-issue":{"issue":"6797","published-print":{"date-parts":[[2000,8,17]]}},"alternative-id":["BF35021219"],"URL":"https:\/\/doi.org\/10.1038\/35021219","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,8,17]]},"assertion":[{"value":"17 August 2000","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}