{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:46:48Z","timestamp":1790952408121,"version":"4.1.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"18","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R03AI141950"],"award-info":[{"award-number":["R03AI141950"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008569","name":"Oklahoma Center for the Advancement of Science and Technology","doi-asserted-by":"publisher","award":["HR19-080"],"award-info":[{"award-number":["HR19-080"]}],"id":[{"id":"10.13039\/100008569","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Faculty Investment Award, University of Oklahoma"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Appl Microbiol Biotechnol"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n<jats:title>Abstract<\/jats:title>\n<jats:p>Daptomycin is a last resort antibiotic for the treatment of infections caused by many Gram-positive bacterial strains, including vancomycin-resistant <jats:italic>Enterococcus<\/jats:italic> (VRE) and methicillin- and vancomycin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA and VRSA). However, the emergence of daptomycin-resistant strains of <jats:italic>S. aureus<\/jats:italic> and <jats:italic>Enterococcus<\/jats:italic> in recent years has renewed interest in synthesizing daptomycin analogs to overcome resistance mechanisms. Within this context, three aromatic prenyltransferases have been shown to accept daptomycin as a substrate, and the resulting prenylated analog was shown to be more potent against Gram-positive strains than the parent compound. Consequently, utilizing prenyltransferases to derivatize daptomycin offered an attractive alternative to traditional synthetic approaches, especially given the molecule\u2019s structural complexity. Herein, we report exploiting the ability of prenyltransferase CdpNPT to synthesize alkyl-diversified daptomycin analogs in combination with a library of synthetic non-native alkyl-pyrophosphates. The results revealed that CdpNPT can transfer a variety of alkyl groups onto daptomycin\u2019s tryptophan residue using the corresponding alkyl-pyrophosphates, while subsequent scaled-up reactions suggested that the enzyme can alkylate the N1, C2, C5, and C6 positions of the indole ring. In vitro antibacterial activity assays using 16 daptomycin analogs revealed that some of the analogs displayed 2\u201380-fold improvements in potency against MRSA, VRE, and daptomycin-resistant strains of <jats:italic>S. aureus<\/jats:italic> and <jats:italic>Enterococcus faecalis<\/jats:italic>. Thus, along with the new potent analogs, these findings have established that the regio-chemistry of alkyl substitution on the tryptophan residue can modulate daptomycin\u2019s potency. With additional protein engineering to improve the regio-selectivity, the described method has the potential to become a powerful tool for diversifying complex indole-containing molecules.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Key points<\/jats:title>\n<jats:p><jats:italic>\u2022 CdpNPT displays impressive donor promiscuity with daptomycin as the acceptor.<\/jats:italic><\/jats:p>\n<jats:p><jats:italic>\u2022 CdpNPT catalyzes N1-, C2-, C5-, and C6-alkylation on daptomycin\u2019s tryptophan residue.<\/jats:italic><\/jats:p>\n<jats:p><jats:italic>\u2022 Differential alkylation of daptomycin\u2019s tryptophan residue modulates its activity.<\/jats:italic><\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s00253-020-10790-x","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T07:38:12Z","timestamp":1595921892000},"page":"7853-7865","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Chemoenzymatic synthesis of daptomycin analogs active against daptomycin-resistant strains"],"prefix":"10.1007","volume":"104","author":[{"given":"Erin M.","family":"Scull","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrasekhar","family":"Bandari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce P.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Tonelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlan","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Cichewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0960-4794","authenticated-orcid":false,"given":"Shanteri","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"issue":"12","key":"10790_CR1","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1086\/420818","volume":"38","author":"RD Arbeit","year":"2004","unstructured":"Arbeit RD, Maki D, Tally FP, Campanaro E, Eisenstein BI (2004) The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis 38(12):1673\u20131681. https:\/\/doi.org\/10.1086\/420818","journal-title":"Clin Infect Dis"},{"key":"10790_CR2","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1039\/b402722a","volume":"2","author":"L-J Ball","year":"2004","unstructured":"Ball L-J, Goult CM, Donarski JA, Micklefield J, Ramesh V (2004) NMR structure determination and calcium binding effects of lipopeptide antibiotic daptomycin. Org Biomol Chem 2:1872\u20131878. https:\/\/doi.org\/10.1039\/b402722a","journal-title":"Org Biomol Chem"},{"issue":"23","key":"10790_CR3","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.1002\/cbic.201700469","volume":"18","author":"C Bandari","year":"2017","unstructured":"Bandari C, Scull EM, Masterson JM, Tran RHQ, Foster SB, Nicholas KM, Singh S (2017) Determination of alkyl-donor promiscuity of tyrosine-O-prenyltransferase SirD from Leptosphaeria maculans. ChemBioChem 18(23):2323\u20132327. https:\/\/doi.org\/10.1002\/cbic.201700469","journal-title":"ChemBioChem"},{"issue":"8","key":"10790_CR4","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1039\/c9md00177h","volume":"10","author":"C Bandari","year":"2019","unstructured":"Bandari C, Scull EM, Bavineni T, Nimmo SL, Gardner ED, Bensen RC, Burgett AW, Singh S (2019) FgaPT2, a biocatalytic tool for alkyl-diversification of indole natural products. MedChemComm 10(8):1465\u20131475. https:\/\/doi.org\/10.1039\/c9md00177h","journal-title":"MedChemComm"},{"key":"10790_CR5","doi-asserted-by":"publisher","unstructured":"Barnawi G, Noden M, Taylor R, Lohani C, Beriashvili D, Palmer M, Taylor SD (2018) An entirely fmoc solid phase approach to the synthesis of daptomycin analogs. Pept Sci:e23094. https:\/\/doi.org\/10.1002\/bip.23094","DOI":"10.1002\/bip.23094"},{"key":"10790_CR6","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/j.1749-6632.2012.06819.x","volume":"1277","author":"AS Bayer","year":"2013","unstructured":"Bayer AS, Schneider T, Sahl HG (2013) Mechanisms of daptomycin resistance in Staphylococcus aureus: role of the cell membrane and cell wall. Ann N Y Acad Sci 1277:139\u2013158. https:\/\/doi.org\/10.1111\/j.1749-6632.2012.06819.x","journal-title":"Ann N Y Acad Sci"},{"issue":"7","key":"10790_CR7","doi-asserted-by":"publisher","first-page":"AAC.00023-18","DOI":"10.1128\/aac.00023-18","volume":"62","author":"R Boudjemaa","year":"2018","unstructured":"Boudjemaa R, Cabriel C, Dubois-Brissonnet F, Bourg N, Dupuis G, Gruss A, L\u00e9v\u00eaque-Fort S, Briandet R, Fontaine-Aupart M-P, Steenkeste K (2018) Impact of bacterial membrane fatty acid composition on the failure of daptomycin to kill Staphylococcus aureus. Antimicrob Agents Chemother 62(7):AAC.00023-18. https:\/\/doi.org\/10.1128\/aac.00023-18","journal-title":"Antimicrob Agents Chemother"},{"issue":"5","key":"10790_CR8","first-page":"282","volume":"33","author":"NH Chan Tompkins","year":"2008","unstructured":"Chan Tompkins NH, Harnicar SJ (2008) Prescribing trends with daptomycin (Cubicin) for the treatment of gram-positive infections. Pharm Ther 33(5):282\u2013288","journal-title":"Pharm Ther"},{"issue":"10","key":"10790_CR9","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.1128\/aac.48.10.3928-3933.2004","volume":"48","author":"P Cottagnoud","year":"2004","unstructured":"Cottagnoud P, Pfister M, Acosta F, Cottagnoud M, Flatz L, Kuhn F, Muller HP, Stucki A (2004) Daptomycin is highly efficacious against penicillin-resistant and penicillin- and quinolone-resistant Pneumococci in experimental meningitis. Antimicrob Agents Chemother 48(10):3928\u20133933. https:\/\/doi.org\/10.1128\/aac.48.10.3928-3933.2004","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"10790_CR10","doi-asserted-by":"publisher","first-page":"761","DOI":"10.7164\/antibiotics.40.761","volume":"40","author":"M Debono","year":"1987","unstructured":"Debono M, Barnhart M, Carrell CB, Hoffmann JA, Occolowitz JL, Abbott BJ, Fukuda DS, Hamill RL, Biemann K, Herlihy WC (1987) A21978C, a complex of new acidic peptide antibiotics. Isolation, chemistry, and mass spectral structure elucidation. J Antibiot 40(6):761\u2013777. https:\/\/doi.org\/10.7164\/antibiotics.40.761","journal-title":"J Antibiot"},{"issue":"8","key":"10790_CR11","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.7164\/antibiotics.41.1093","volume":"41","author":"M Debono","year":"1988","unstructured":"Debono M, Abbott BJ, Molloy RM, Fukuda DS, Hunt AH, Daupert VM, Counter FT, Ott JL, Carrell CB, Howard LC, Boeck LVD, Hamill RL (1988) Enzymatic and chemical modifications of lipopeptide antibiotic A21978C: the synthesis and evaluation of daptomycin (LY146032). J Antibiot 41(8):1093\u20131105. https:\/\/doi.org\/10.7164\/antibiotics.41.1093","journal-title":"J Antibiot"},{"key":"10790_CR12","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/BF00197809","volume":"6","author":"F Delaglio","year":"1995","unstructured":"Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfiefer J, Bax A (1995) NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR 6:277\u2013293. https:\/\/doi.org\/10.1007\/BF00197809","journal-title":"J Biomol NMR"},{"issue":"Pt 9","key":"10790_CR13","doi-asserted-by":"publisher","first-page":"2872","DOI":"10.1099\/mic.0.2008\/020685-0","volume":"154","author":"S Doekel","year":"2008","unstructured":"Doekel S, Coeffet-Le Gal MF, Gu JQ, Chu M, Baltz RH, Brian P (2008) Non-ribosomal peptide synthetase module fusions to produce derivatives of daptomycin in Streptomyces roseosporus. Microbiology 154(Pt 9):2872\u20132880. https:\/\/doi.org\/10.1099\/mic.0.2008\/020685-0","journal-title":"Microbiology"},{"issue":"Suppl 1","key":"10790_CR14","doi-asserted-by":"publisher","first-page":"S10","DOI":"10.1086\/647938","volume":"50","author":"BI Eisenstein","year":"2010","unstructured":"Eisenstein BI, Oleson FB Jr, Baltz RH (2010) Daptomycin: from the mountain to the clinic, with essential help from Francis Tally, MD. Clin Infect Dis 50(Suppl 1):S10\u2013S15. https:\/\/doi.org\/10.1086\/647938","journal-title":"Clin Infect Dis"},{"issue":"4","key":"10790_CR15","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/nchembio.2285","volume":"13","author":"SI Elshahawi","year":"2017","unstructured":"Elshahawi SI, Cao H, Shaaban KA, Ponomareva LV, Subramanian T, Farman ML, Spielmann HP, Phillips GN, Thorson JS, Singh S (2017) Structure and specificity of a permissive bacterial C-prenyltransferase. Nat Chem Biol 13(4):366\u2013368. https:\/\/doi.org\/10.1038\/nchembio.2285","journal-title":"Nat Chem Biol"},{"issue":"7","key":"10790_CR16","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1056\/NEJMoa053783","volume":"355","author":"J Fowler","year":"2006","unstructured":"Fowler J, VG, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA, Cabell CH, Link AS, De Meyer I, Filler SG, Zervos M, Cook P, Parsonnet J, Bernstein JM, Price CS, Forrest GN, F\u00e4tkenheuer G, Gareca M, Rehm SJ, Brodt HR, Tice A, Cosgrove SE (2006) Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 355(7):653\u2013665. https:\/\/doi.org\/10.1056\/NEJMoa053783","journal-title":"N Engl J Med"},{"issue":"6","key":"10790_CR17","first-page":"391","volume":"30","author":"N Gom\u00e9z Casanova","year":"2017","unstructured":"Gom\u00e9z Casanova N, Siller Ruiz M, Mu\u00f1oz Bellido JL (2017) Mechanisms of resistance to daptomycin in Staphylococcus aureus. Rev Esp Quimioter 30(6):391\u2013396","journal-title":"Rev Esp Quimioter"},{"key":"10790_CR18","doi-asserted-by":"publisher","unstructured":"Gray DA, Wenzel M (2020) More than a pore: a current perspective on the in vivo mode of action of the lipopeptide antibiotic daptomycin. Antibiotics (Basel) 9(1). https:\/\/doi.org\/10.3390\/antibiotics9010017","DOI":"10.3390\/antibiotics9010017"},{"issue":"51","key":"10790_CR19","doi-asserted-by":"publisher","first-page":"17025","DOI":"10.1021\/ja045455t","volume":"126","author":"J Gr\u00fcnewald","year":"2004","unstructured":"Gr\u00fcnewald J, Sieber SA, Mahlert C, Linne U, Marahiel MA (2004) Synthesis and derivatization of daptomycin: a chemoenzymatic route to acidic lipopeptide antibiotics. J Am Chem Soc 126(51):17025\u201317031. https:\/\/doi.org\/10.1021\/ja045455t","journal-title":"J Am Chem Soc"},{"issue":"19","key":"10790_CR20","doi-asserted-by":"publisher","first-page":"6248","DOI":"10.1016\/j.bmcl.2012.08.013","volume":"22","author":"Y He","year":"2012","unstructured":"He Y, Li J, Yin N, Herradura PS, Martel L, Zhang Y, Pearson AL, Kulkarni V, Mascio C, Howland K, Silverman JA, Keith DD, Metcalf CA (2012) Reduced pulmonary surfactant interaction of daptomycin analogs via tryptophan replacement with alternative amino acids. Bioorg Med Chem Lett 22(19):6248\u20136251. https:\/\/doi.org\/10.1016\/j.bmcl.2012.08.013","journal-title":"Bioorg Med Chem Lett"},{"issue":"23","key":"10790_CR21","doi-asserted-by":"publisher","first-page":"4187","DOI":"10.1016\/j.bmcl.2003.07.019","volume":"13","author":"J Hill","year":"2003","unstructured":"Hill J, Siedlecki J, Parr I, Morytko M, Yu X, Zhang Y, Silverman J, Controneo N, Laganas V, Li T, Lai J-J, Keith D, Shimer G, Finn J (2003) Synthesis and biological activity of N-acylated ornithine analogues of daptomycin. Bioorg Med Chem Lett 13(23):4187\u20134191. https:\/\/doi.org\/10.1016\/j.bmcl.2003.07.019","journal-title":"Bioorg Med Chem Lett"},{"key":"10790_CR22","doi-asserted-by":"publisher","first-page":"4383","DOI":"10.1007\/s00253-020-10529-8","volume":"104","author":"BP Johnson","year":"2020","unstructured":"Johnson BP, Scull EM, Dimas DA, Bavineni T, Bandari C, Batchev AL, Gardner ED, Nimmo SL, Singh S (2020) Acceptor substrate determines donor specificity of an aromatic prenyltransferase: expanding the biocatalytic potential of NphB. Appl Microbiol Biotechnol 104:4383\u20134395. https:\/\/doi.org\/10.1007\/s00253-020-10529-8","journal-title":"Appl Microbiol Biotechnol"},{"issue":"7","key":"10790_CR23","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.chembiol.2004.04.020","volume":"11","author":"D Jung","year":"2004","unstructured":"Jung D, Rozek A, Okon M, Hancock RE (2004) Structural transitions as determinants of the action of the calcium-dependent antibiotic daptomycin. Chem Biol 11(7):949\u2013957. https:\/\/doi.org\/10.1016\/j.chembiol.2004.04.020","journal-title":"Chem Biol"},{"issue":"16","key":"10790_CR24","doi-asserted-by":"publisher","first-page":"6272","DOI":"10.1021\/ja4012468","volume":"135","author":"HY Lam","year":"2013","unstructured":"Lam HY, Zhang Y, Liu H, Xu J, Wong CTT, Xu C, Li X (2013) Total synthesis of daptomycin by cyclization via a chemoselective serine ligation. J Am Chem Soc 135(16):6272\u20136279. https:\/\/doi.org\/10.1021\/ja4012468","journal-title":"J Am Chem Soc"},{"issue":"8","key":"10790_CR25","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1093\/bioinformatics\/btu830","volume":"31","author":"W Lee","year":"2015","unstructured":"Lee W, Tonelli M, Markley JL (2015) NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy. Bioinformatics 31(8):1325\u20131327. https:\/\/doi.org\/10.1093\/bioinformatics\/btu830","journal-title":"Bioinformatics"},{"issue":"22","key":"10790_CR26","doi-asserted-by":"publisher","first-page":"5834","DOI":"10.1021\/ol4029012","volume":"15","author":"M Liebhold","year":"2013","unstructured":"Liebhold M, Li S-M (2013) Regiospecific benzylation of tryptophan derivatives catalyzed by a fungal dimethylallyl transferase. Org Lett 15(22):5834\u20135837. https:\/\/doi.org\/10.1021\/ol4029012","journal-title":"Org Lett"},{"issue":"18","key":"10790_CR27","doi-asserted-by":"publisher","first-page":"4882","DOI":"10.1021\/ol302207r","volume":"14","author":"M Liebhold","year":"2012","unstructured":"Liebhold M, Xie X, Li S-M (2012) Expansion of enzymatic Friedel\u2013crafts alkylation on indoles: acceptance of unnatural \u03b2-unsaturated allyl diphosphates by dimethylallyl-tryptophan synthases. Org Lett 14(18):4882\u20134885. https:\/\/doi.org\/10.1021\/ol302207r","journal-title":"Org Lett"},{"issue":"12","key":"10790_CR28","doi-asserted-by":"publisher","first-page":"3062","DOI":"10.1021\/ol401247s","volume":"15","author":"M Liebhold","year":"2013","unstructured":"Liebhold M, Xie X, Li S-M (2013) Breaking cyclic dipeptide prenyltransferase regioselectivity by unnatural alkyl donors. Org Lett 15(12):3062\u20133065. https:\/\/doi.org\/10.1021\/ol401247s","journal-title":"Org Lett"},{"key":"10790_CR29","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.bmcl.2016.12.046","volume":"27","author":"DA Lin","year":"2016","unstructured":"Lin DA, Lam HY, Han W, Cotroneo N, Pandya BA, Li X (2016) Structure-activity relationship of daptomycin analogues with substitution at (2S,3R)-3-methyl glutamic acid position. Bioorg Med Chem Lett 27:456\u2013459. https:\/\/doi.org\/10.1016\/j.bmcl.2016.12.046","journal-title":"Bioorg Med Chem Lett"},{"issue":"23","key":"10790_CR30","doi-asserted-by":"publisher","first-page":"5490","DOI":"10.1016\/j.bmcl.2015.10.072","volume":"25","author":"CR Lohani","year":"2015","unstructured":"Lohani CR, Taylor R, Palmer M, Taylor SD (2015a) Solid-phase synthesis and in vitro biological activity of a Thr4\u2192Ser4 analog of daptomycin. Bioorg Med Chem Lett 25(23):5490\u20135494. https:\/\/doi.org\/10.1016\/j.bmcl.2015.10.072","journal-title":"Bioorg Med Chem Lett"},{"issue":"3","key":"10790_CR31","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1021\/acs.orglett.5b00043","volume":"17","author":"CR Lohani","year":"2015","unstructured":"Lohani CR, Taylor R, Palmer M, Taylor SD (2015b) Solid-phase total synthesis of daptomycin and analogs. Org Lett 17(3):748\u2013751. https:\/\/doi.org\/10.1021\/acs.orglett.5b00043","journal-title":"Org Lett"},{"issue":"5","key":"10790_CR32","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1099\/mic.0.27757-0","volume":"151","author":"V Miao","year":"2005","unstructured":"Miao V, Co\u00ebffet-LeGal M, Brian P, Brost R, Penn J, Whiting A, Martin S, Ford R, Parr I, Bouchard M, Silva CJ, Wrigley SK, Baltz RH (2005) Daptomycin biosynthesis in Streptomyces roseosporus: cloning and analysis of the gene cluster and revision of peptide stereochemistry. Microbiology 151(5):1507\u20131523. https:\/\/doi.org\/10.1099\/mic.0.27757-0","journal-title":"Microbiology"},{"issue":"3","key":"10790_CR33","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.chembiol.2005.12.012","volume":"13","author":"V Miao","year":"2006","unstructured":"Miao V, Co\u00ebffet-Le Gal M-F, Nguyen K, Brian P, Penn J, Whiting A, Steele J, Kau D, Martin S, Ford R, Gibson T, Bouchard M, Wrigley SK, Baltz RH (2006) Genetic engineering in Streptomyces roseosporus to produce hybrid lipopeptide antibiotics. Chem Biol 13(3):269\u2013276. https:\/\/doi.org\/10.1016\/j.chembiol.2005.12.012","journal-title":"Chem Biol"},{"issue":"45","key":"10790_CR34","doi-asserted-by":"publisher","first-page":"E7077","DOI":"10.1073\/pnas.1611173113","volume":"113","author":"A M\u00fcller","year":"2016","unstructured":"M\u00fcller A, Wenzel M, Strahl H, Grein F, Saaki TNV, Kohl B, Siersma T, Bandow JE, Sahl HG, Schneider T, Hamoen LW (2016) Daptomycin inhibits cell envelope synthesis by interfering with fluid membrane microdomains. Proc Natl Acad Sci U S A 113(45):E7077\u2013E7086. https:\/\/doi.org\/10.1073\/pnas.1611173113","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"10790_CR35","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1186\/s12974-018-1272-8","volume":"15","author":"L Muri","year":"2018","unstructured":"Muri L, Grandgirard D, Buri M, Perny M, Leib SL (2018) Combined effect of non-bacteriolytic antibiotic and inhibition of matrix metalloproteinases prevents brain injury and preserves learning, memory and hearing function in experimental paediatric pneumococcal meningitis. J Neuroinflammation 15(1):233. https:\/\/doi.org\/10.1186\/s12974-018-1272-8","journal-title":"J Neuroinflammation"},{"key":"10790_CR36","doi-asserted-by":"publisher","first-page":"16194","DOI":"10.1038\/nmicrobiol.2016.194","volume":"2","author":"V Pader","year":"2016","unstructured":"Pader V, Hakim S, Painter KL, Wigneshweraraj S, Clarke TB, Edwards AM (2016) Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids. Nat Microbiol 2:16194. https:\/\/doi.org\/10.1038\/nmicrobiol.2016.194","journal-title":"Nat Microbiol"},{"issue":"17","key":"10790_CR37","doi-asserted-by":"publisher","first-page":"4494","DOI":"10.1128\/JB.00011-12","volume":"194","author":"J Pogliano","year":"2012","unstructured":"Pogliano J, Pogliano N, Silverman JA (2012) Daptomycin-mediated reorganization of membrane architecture causes mislocalization of essential cell division proteins. J Bacteriol 194(17):4494\u20134504. https:\/\/doi.org\/10.1128\/JB.00011-12","journal-title":"J Bacteriol"},{"issue":"36","key":"10790_CR38","doi-asserted-by":"publisher","first-page":"27501","DOI":"10.1074\/jbc.r110.128181","volume":"285","author":"L Robbel","year":"2010","unstructured":"Robbel L, Marahiel MA (2010) Daptomycin, a bacterial lipopeptide synthesized by a nonribosomal machinery. J Biol Chem 285(36):27501\u201327508. https:\/\/doi.org\/10.1074\/jbc.r110.128181","journal-title":"J Biol Chem"},{"issue":"Suppl. 6","key":"10790_CR39","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/j.1469-0691.2009.03054.x","volume":"15","author":"G Sakoulas","year":"2009","unstructured":"Sakoulas G (2009) Clinical outcomes with daptomycin: a post-marketing, real-world evaluation. Clin Microbiol Infect 15(Suppl. 6):11\u201316. https:\/\/doi.org\/10.1111\/j.1469-0691.2009.03054.x","journal-title":"Clin Microbiol Infect"},{"issue":"1","key":"10790_CR40","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.jmb.2012.05.033","volume":"422","author":"JM Schuller","year":"2012","unstructured":"Schuller JM, Zocher G, Liebhold M, Xie X, Stahl M, Li SM, Stehle T (2012) Structure and catalytic mechanism of a cyclic dipeptide prenyltransferase with broad substrate promiscuity. J Mol Biol 422(1):87\u201399. https:\/\/doi.org\/10.1016\/j.jmb.2012.05.033","journal-title":"J Mol Biol"},{"issue":"23","key":"10790_CR41","doi-asserted-by":"publisher","first-page":"4245","DOI":"10.1016\/j.bmcl.2003.07.025","volume":"13","author":"J Siedlecki","year":"2003","unstructured":"Siedlecki J, Hill J, Parr I, Yu X, Morytko M, Zhang Y, Silverman J, Controneo N, Laganas V, Li T, Li J, Keith D, Shimer G, Finn J (2003) Array synthesis of novel lipodepsipeptide. Bioorg Med Chem Lett 13(23):4245\u20134249. https:\/\/doi.org\/10.1016\/j.bmcl.2003.07.025","journal-title":"Bioorg Med Chem Lett"},{"issue":"12","key":"10790_CR42","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1086\/430352","volume":"191","author":"JA Silverman","year":"2005","unstructured":"Silverman JA, I. ML, Van Praagh ADG, Li T, Alder J (2005) Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. J Infect Dis 191(12):2149\u20132152. https:\/\/doi.org\/10.1086\/430352","journal-title":"J Infect Dis"},{"issue":"3","key":"10790_CR43","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1093\/jac\/dkh546","volume":"55","author":"JN Steenbergen","year":"2005","unstructured":"Steenbergen JN, Alder J, Thorne GM, Tally FP (2005) Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections. J Antimicrob Chemother 55(3):283\u2013288. https:\/\/doi.org\/10.1093\/jac\/dkh546","journal-title":"J Antimicrob Chemother"},{"issue":"4","key":"10790_CR44","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1093\/jac\/46.4.523","volume":"46","author":"FP Tally","year":"2000","unstructured":"Tally FP, Debruin MF (2000) Development of daptomycin for Gram-positive infections. J Antimicrob Chemother 46(4):523\u2013526. https:\/\/doi.org\/10.1093\/jac\/46.4.523","journal-title":"J Antimicrob Chemother"},{"issue":"1","key":"10790_CR45","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1039\/c4np00099d","volume":"32","author":"ME Tanner","year":"2015","unstructured":"Tanner ME (2015) Mechanistic studies on the indole prenyltransferases. Nat Prod Rep 32(1):88\u2013101. https:\/\/doi.org\/10.1039\/c4np00099d","journal-title":"Nat Prod Rep"},{"issue":"11","key":"10790_CR46","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1021\/acsinfecdis.7b00138","volume":"3","author":"R Taylor","year":"2017","unstructured":"Taylor R, Beriashvili D, Taylor S, Palmer M (2017) Daptomycin pore formation is restricted by lipid acyl chain composition. ACS Infect Dis 3(11):797\u2013801. https:\/\/doi.org\/10.1021\/acsinfecdis.7b00138","journal-title":"ACS Infect Dis"},{"issue":"10","key":"10790_CR47","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1007\/s00018-008-7579-3","volume":"65","author":"M Tello","year":"2008","unstructured":"Tello M, Kuzuyama T, Heide L, Noel JP, Richard SB (2008) The ABBA family of aromatic prenyltransferases: broadening natural product diversity. Cell Mol Life Sci 65(10):1459\u20131463. https:\/\/doi.org\/10.1007\/s00018-008-7579-3","journal-title":"Cell Mol Life Sci"},{"key":"10790_CR48","doi-asserted-by":"publisher","first-page":"202","DOI":"10.2174\/1389557511209030202","volume":"12","author":"C Vilhena","year":"2012","unstructured":"Vilhena C, Bettencourt A (2012) Daptomycin: a review of properties, clinical use, drug delivery and resistance. Mini-Rev Med Chem 12:202\u2013209. https:\/\/doi.org\/10.2174\/1389557511209030202","journal-title":"Mini-Rev Med Chem"},{"issue":"5","key":"10790_CR49","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1002\/adsc.201400958","volume":"357","author":"J Winkelblech","year":"2015","unstructured":"Winkelblech J, Liebhold M, Gunera J, Xie X, Kolb P, Li S-M (2015) Tryptophan C5-, C6-, and C7-prenylating enzymes displaying a preference for C-6 of the indole ring in the presence of unnatural dimethylallyl diphosphate analogues. Adv Synth Cat 357(5):975\u2013986. https:\/\/doi.org\/10.1002\/adsc.201400958","journal-title":"Adv Synth Cat"},{"issue":"12","key":"10790_CR50","doi-asserted-by":"publisher","first-page":"5137","DOI":"10.1021\/acs.jmedchem.5b00366","volume":"58","author":"N Yin","year":"2015","unstructured":"Yin N, Li J, He Y, Herradura P, Pearson A, Mesleh MF, Mascio CT, Howland K, Steenbergen J, Thorne GM, Citron D, Van Praagh AD, Mortin LI, Keith D, Silverman J, Metcalf C (2015) Structure-activity relationship studies of a series of semisynthetic lipopeptides leading to the discovery of surotomycin, a novel cyclic lipopeptide being developed for the treatment of Clostridium difficile-associated diarrhea. J Med Chem 58(12):5137\u20135142. https:\/\/doi.org\/10.1021\/acs.jmedchem.5b00366","journal-title":"J Med Chem"},{"issue":"3","key":"10790_CR51","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s10295-009-0667-z","volume":"37","author":"J You","year":"2010","unstructured":"You J, Dai H, Chen Z, Liu G, He Z, Song F, Yang X, Fu H, Zhang L, Chen X (2010) Trichoderone, a novel cytotoxic cyclopentenone and cholesta-7, 22-diene-3\u03b2, 5\u03b1, 6\u03b2-triol, with new activities from the marine-derived fungus Trichoderma sp. J Ind Microbiol Biotechnol 37(3):245\u2013252. https:\/\/doi.org\/10.1007\/s10295-009-0667-z","journal-title":"J Ind Microbiol Biotechnol"},{"issue":"17","key":"10790_CR52","doi-asserted-by":"publisher","first-page":"7115","DOI":"10.1007\/s00253-015-6452-1","volume":"99","author":"H Yu","year":"2015","unstructured":"Yu H, Liebhold M, Xie X, Li SM (2015) Tyrosine O-prenyltransferases TyrPT and SirD displaying similar behavior toward unnatural alkyl or benzyl diphosphate as their natural prenyl donor dimethylallyl diphosphate. Appl Microbiol Biotechnol 99(17):7115\u20137124. https:\/\/doi.org\/10.1007\/s00253-015-6452-1","journal-title":"Appl Microbiol Biotechnol"},{"issue":"17","key":"10790_CR53","doi-asserted-by":"publisher","first-page":"11584","DOI":"10.1074\/jbc.M114.554444","volume":"289","author":"T Zhang","year":"2014","unstructured":"Zhang T, Muraih JK, Tishbi N, Herskowitz J, Victor RL, Silverman J, Uwumarenogie S, Taylor SD, Palmer M, Mintzer E (2014) Cardiolipin prevents membrane translocation and permeabilization by daptomycin. J Biol Chem 289(17):11584\u201311591. https:\/\/doi.org\/10.1074\/jbc.M114.554444","journal-title":"J Biol Chem"}],"container-title":["Applied Microbiology and Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00253-020-10790-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00253-020-10790-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00253-020-10790-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T23:23:21Z","timestamp":1627428201000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00253-020-10790-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,28]]},"references-count":53,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10790"],"URL":"https:\/\/doi.org\/10.1007\/s00253-020-10790-x","relation":{},"ISSN":["0175-7598","1432-0614"],"issn-type":[{"value":"0175-7598","type":"print"},{"value":"1432-0614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,28]]},"assertion":[{"value":"21 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"N\/A","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statements"}},{"value":"N\/A","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}}]}}