细菌脂蛋白生物合成调控研究进展
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摘要
细菌脂蛋白是一组具有多种功能的膜蛋白。由于其广泛的功能,这些蛋白质对细菌的正常生长、分化和发育是必须的。脂蛋白的经典生物合成路径需要细胞质膜的3种酶:前脂蛋白二酰甘油基转移酶(Lgt),脂蛋白信号肽酶Ⅱ(LspA)和脂蛋白N-酰基转移酶(Lnt)相继发挥催化作用,产生成熟的三酰化脂蛋白。这3种酶的缺失会导致革兰阴性菌的死亡及革兰阳性菌活力和致病能力的下降,并且这3种酶是原核生物所特有的,在人体中无同源类似物。因此这些酶是下一代广谱抗生素研发的潜在靶标。近几年来,这些酶的晶体结构已被相继解析出来,从而可以开展基于结构的药物设计。本文主要综述细菌脂蛋白生物合成路径以所涉及到的3种酶的晶体结构和生物学功能。
Bacterial lipoprotein are a set of lipid-modified membrane-anchored proteins with many different functions. These proteins are essential for bacterial growth, division and development because of their broad biological functions. The canonical biosynthesis pathway of lipoproteins need three key enzymes embedded in the cytoplasm(prolipoproteindiacylglyceryl transferase, lipoprotein signal peptidase II, and apolipoprotein N-acyltransferase) function sequentially to produce mature triacylated lipoproteins. The absence of these enzymes results in the death of Gram-negative bacteria and decrease in the vitality and pathogenicity of Gram-positive bacteria, and these enzymes are unique to prokaryotes, having no equivalents in humans. So these enzymes present excellent potential targets for the next generation of broad spectrum antibiotics. In recent years, the crystal structure of these enzymes has been successively resolved, allowing structure-based drug design. Hence, this review highlights the crystal structure as well as biological function of three enzymes involved in biosynthesis pathway of bacterial lipoproteins.
Bacterial lipoprotein are a set of lipid-modified membrane-anchored proteins with many different functions. These proteins are essential for bacterial growth, division and development because of their broad biological functions. The canonical biosynthesis pathway of lipoproteins need three key enzymes embedded in the cytoplasm(prolipoproteindiacylglyceryl transferase, lipoprotein signal peptidase II, and apolipoprotein N-acyltransferase) function sequentially to produce mature triacylated lipoproteins. The absence of these enzymes results in the death of Gram-negative bacteria and decrease in the vitality and pathogenicity of Gram-positive bacteria, and these enzymes are unique to prokaryotes, having no equivalents in humans. So these enzymes present excellent potential targets for the next generation of broad spectrum antibiotics. In recent years, the crystal structure of these enzymes has been successively resolved, allowing structure-based drug design. Hence, this review highlights the crystal structure as well as biological function of three enzymes involved in biosynthesis pathway of bacterial lipoproteins.
引文
[1]Pugsley A P.The complete general secretory pathway in Gramnegative bacteria[J].Microbiol Rev,1993,57(1):50-108.
[2]Sutcliffe I C,Russell R.Lipoproteins of Gram-positive bacteria[J].J Bacteriol,1995,177(5):1123-1128.
[3]Hutchings M I,Almer T,Harrington D J,et al.Lipoprotein biogenesis in Gram-positive bacteria:Knowing when to hold'em,knowing when to fold'em[J].Trends Microbiol,2009,17(1):13-21
[4]Khandavilli S,Homer K A,Yuste J,et al.Maturation of Streptococcus pneumoniae lipoproteins by a type II signal peptidase is required for ABC transporter function and full virulence[J].Mol Microbiol,2008,67(3):541-557.
[5]Iwasaki A,Medzhitov R.Regulation of adaptive immunity by the innate immune system[J].Science,2010,327(5963):291-295.
[6]Sutcliffe I C,Harrington D J,Hutchings M I.Aphylum level analysis reveals lipoprotein biosynthesis to be a fundamental property of bacteria[J].Protein Cell,2012,3(3):163-170.
[7]Hantke,Braun V.Covalent binding of lipid to protein.Diglyceride and amide-linked fatty acid at the N-terminal end of the murein-lipoprotein of the Escherichia coli outer membrane[J].Eur J Biochem,1973,34(2):284-296.
[8]Driessen A J,Nouwen N.Protein translocation across thebacterial cytoplasmic membrane[J].Ann Rev Biochem,2008,77(1):643-667.
[9]Berks B C,Palmer T,Sargent F.Protein targeting by thebacterial twin-arginine translocation(Tat)pathway[J].Curr Opin Microbiol,2005,8(2):174-181.
[10]Guotao Mao,Yan Zhao,Xuejun Zhang,et al.Crystal structure of E.coli lipoprotein diacylglyceryl transferase[J].Nat Commun,2016,7:10198-10210.
[11]Hayashi S,Chang S Y,Chang S,et al.Modification and processing of internalized signal sequences of prolipoprotein in Escherichia coli and in Bacillus subtilis[J].J Biol Chem,1985,260(9):5753-5759
[12]Navarre W W,Daefler S,Schneewind O.Cell wall sorting of lipoproteins in Staphylococcus aureus[J].J Bacteriol,178,178(2):441-446.
[13]Babu M M,Priya M L,Selvan A T,et al.A database ofbacterial lipoproteins(DOLOP)with functionalassignments to predicted lipoproteins[J].J Bacteriol,2006,188(8):2761-2773.
[14]Gan K,Sankaran K,Williams M G,et al.The umpAgene of Escherichia coli encodes phosphatidylglycerol:Prolipoprotein diacylglyceryl transferase(lgt)and regulates thymidylate synthase levels through translational coupling[J].J Bacteriol,1995,177(7):1879-1882.
[15]Tokunaga M,Loranger J M,Wu H C.Prolipoprotein modificationand processing enzymes in Escherichia coli[J].J Biol Chem,1984,259(6):3825-3830.
[16]T h o m p s o n B J,Wi d d i c k D A,H i c k s M G,e t a l.Investigating lipoprotein biogenesis and function in the model Gram-positive bacterium Streptomyces coelicolor[J].Mol Microbiol,2010,77(4):943-957.
[17]Sankaran K,Wu H C.Lipid modification of bacterial prolipoprotein:Transfer of diacylglycerylmoiety from phosphatidylglycerol[J].J Biol Chem,1994,269(31):19701-19706.
[18]Pailler J,Aucher W,Pires M,et al.Phosphatidylglycerol:Prolipoproteindiacylglyceryltransferase(Lgt)of E.coli has seven transmembrane segments and its essentialresidues are embedded in the membrane[J].J Bacteriol,2012,194(9):2142-2151.
[19]Sankaran K,Gan K,Rash B,et al.Roles of histidine-103and tyrosine-235 in the function of the prelipoprotein diacylglyceryl transferase of Escherichia coli[J].J Bacteriol,1997,179(9):2944-2948.
[20]Malinverni J C,Werner J,Kim S,et al.YfiO stabilizes the YaeT complex and is essential for outer membrane protein assembly in Escherichia coli[J].Mol Microbiol,2006,61(1):151-164.
[21]Leskela S,Wahlstrom E,Kontinen V P,et al.Lipid modification of prelipoproteins isdispensable for growth but essential for efficient protein secretion in Bacillus subtilis:characterization of the Lgt gene[J].MolMicrobiol,1999,31(4):1075-1085.
[22]Tjalsma H,Kontinen V P,Pragai Z,et al.The role of lipoprotein processing by signal peptidase II in the Grampositive eubacterium Bacillus subtilis.Signal peptidase II is required for the efficient secretion of alpha-amylase,a nonlipoprotein[J].J Biol Chem,1999,274(3):1698-1707.
[23]Bengtsson J,Karamata D.Bacillus subtilis contains two small c-type cytochromes with homologous heme domains but different types of membrane anchors[J].J Biol Chem,1999,274(37):6179-26184.
[24]Igarashi T.Setlow B,Paidhungat M,et al.Effects of a gerF(lgt)mutation on the germination of spores of Bacillus subtilis[J].J Bacteriol,2004,186(10):2984-2991
[25]Brik A,Wong C H.HIV-1 protease:mechanism and drug discovery[J].Org Biomol Chem,2003,1(1):5-14.
[26]Gerstel B,Loessner M,Wehland J,et al.Inactivation of Lgt allows systematic characterization of lipoproteins from Listeria monocytogenes[J].J Bacteriol,2007,189(2):313-324.
[27]Henneke P,Dramsi S,Mancuso G,et al.Lipoproteins arecritical TLR2 activating toxins in group B streptococcal sepsis[J].J Immunol,2008,180(9):6149-6158.
[28]Denham E L,Ward P N,Leigh J A,et al.Lipoprotein signal peptides are processed by Lsp and Eep of Streptococcus uberis[J].J Bacteriol,2008,190(13):4641-4647.
[29]HamiltonA,Robinson C,Sutcliffeet I C,et al.Mutation of the maturase lipoprotein attenuates the virulence of Streptococcus equi to a greater extent than does loss of general lipoprotein lipidation[J].Infect Immun,2006,74(12):6907-6919.
[30]Remaut H,Fronze R.In bacterial membranes:Structural and molecular biology[J].Caister Academic Press,2014,(243):55-179.
[31]Zuckert W R.Protein trafficking and secretion in bacteria[J].Biochim Biophys Acta,2014,8(1843):1509-1516.
[32]Buddelmeijer N.The molecular mechanism of bacterial lipoprotein modification-how,when and why[J].FEMSMicrobio.Rev,2015,39(2):246-2619.
[33]Kovacs-Simon A,Titball R W,Michell S L.Lipoproteins of bacterial pathogens[J].Infect Immun,2011,79(2):548-561.
[34]Vogeley L,Bailey J,Stansfeld L,et al.Structural basis of lipoprotein signal peptidase II action and inhibition by the antibiotic globomycin[J].Science,2016,351(6275):876.
[35]Inukai M,Enokita R,Torikata A,et al.Globomycin,a new peptideantibiotic with spheroplast-forming activity.I.Taxonomy of producing organisms and fermentation[J].JAntibiot,1978,31(5):410-420.
[36]Dev I K,Harvey R J,Ray P H.Inhibition of prolipoprotein signal peptidase by globomycin[J].J Biol Chem,1985,260(10):5891-5984.
[37]Xiao Y,Wall D.Genetic redundancy,proximity,and functionality of lspA,the target of antibiotic TA,in the Myxococcus xanthus producer strain[J].J Bacteriol,2014,196(6):1174-1183.
[38]Kiho T,Nakayama M,Yasuda K,et al.Synthesis and antimicrobial activity of novel globomycin analogues[J].Bioorg Med Chem Lett,2003,13(14):2315-2318.
[39]Kiho T,Nakayama M,Yasuda K,et al.Structure-activity relationships of globomycin analogues as antibiotics[J].Bioorg Med Chem,2004,12(2):337-361.
[40]Rosenberg E,Dworkin M.Autocides and a paracide,antibiotic TA,produced by Myxococcus xanthus[J].J Ind Microbiol,1996,17(5-6):424-431.
[41]Seiya K,Anna O,Daniel W,et al.Lipoprotein signal peptidase inhibitors with antibiotic properties identified through design of a robust in vitro HT platform[J].Cell Chem Biol,2018,25(3):1-8.
[42]Gupta S D,Wu H C.Identification and subcellular localization of apolipoprotein N-acyltransferase in Escherichia coli[J].FEMS Microbiol Lett,1991,78(1):37-41.
[43]Fukuda A,Matsuyama S,Hara T,et al.Aminoacylation of the N-terminal cysteine is essential for Loldependentrelease of lipoproteins from membranes but does not depend on lipoproteinsorting signals[J].J Biol Chem,2002,277(45):43512-43518.
[44]Gupta S D,DowhamW,Wu H C.Phosphatidylethanolamine is not essential for the N-acylation of apolipoprotein in Escherichia coli[J].J Biol Chem,1991,266(15):9983-9986.
[45]Vidal-Ingigliardi D,Lewenza S,Buddelmeijer N.Identification of essential residues in apolipoprotein N-acyltransferase,a member of the CN hydrolase family[J].J Bacteriol,2007,189(12):4456-4464.
[46]Buddelmeijer N,Young R.The essential Escherichia coli apolipoprotein N-acyltransferase(Lnt)exists as an extracytoplasmic thioester acyl-enzyme intermediate[J].Biochemistry,2010,49(2):341-346.
[47]Hillmann F,Argentini M,Buddelmeijer N.Kinetics and phospholipid specificity of apolipoprotein N-acyltransferase[J].J Biol Chem,2011,286(32):27936-27946.
[48]Tschumi A,Nai C,Auchli Y,et al.Identification of apolipoprotein N-acyltransferase(Lnt)in mycobacteria[J].JBiol Chem,2009,284(40):27146-27156.
[49]Widdick D A,Hicks M G,Thompson B J,et al.Dissecting the complete lipoprotein biogenesis pathway in Streptomyces scabies[J].Mol Microbiol,2011,80(5):1395-1412.
[50]Goren M B.Mycobacterial lipids:selected topics[J].Bacteriol Rev,1972,36(1):33-64.
[51]Jackowski S,Rock C O.Transfer of fatty acids from the1-position of phosp-hatidylethanolamine to the major outer membrane lipoprotein of Escherichia coli[J].J Biol Chem,1986,261(24):11328-11333.
[52]Vidal-Ingigliardi D,Lewenza S,Buddelmeijer N.Identification of essential residues in apolipoprotein N-acyltransferase,a member of the CN hydrolase family[J].J Bacteriol,2007,189(12):4456-4464.
[53]Buddelmeijer N,Young R.The essential Escherichia coli apolipoprotein N-acyltransferase(Lnt)exists as an extra cytoplasmic thioester acyl-enzyme intermediate[J].Biochemistry,2010,49(2):341-346.
[54]Widdick D A,Hicks M G,Thompson B J,et al.Dissecting the complete lipoprotein biogenesis pathway in Streptomyces scabies[J].Mol Microbiol,2011,80(5):1395-1412.
[55]Cameron L N,Michele D,Jeremy M M,et al.Structural insights into lipoprotein N-acylation by Escherichia coli apolipoprotein N-acyltransferase[J].PNAS,2017,114(30):6044-6053.
[2]Sutcliffe I C,Russell R.Lipoproteins of Gram-positive bacteria[J].J Bacteriol,1995,177(5):1123-1128.
[3]Hutchings M I,Almer T,Harrington D J,et al.Lipoprotein biogenesis in Gram-positive bacteria:Knowing when to hold'em,knowing when to fold'em[J].Trends Microbiol,2009,17(1):13-21
[4]Khandavilli S,Homer K A,Yuste J,et al.Maturation of Streptococcus pneumoniae lipoproteins by a type II signal peptidase is required for ABC transporter function and full virulence[J].Mol Microbiol,2008,67(3):541-557.
[5]Iwasaki A,Medzhitov R.Regulation of adaptive immunity by the innate immune system[J].Science,2010,327(5963):291-295.
[6]Sutcliffe I C,Harrington D J,Hutchings M I.Aphylum level analysis reveals lipoprotein biosynthesis to be a fundamental property of bacteria[J].Protein Cell,2012,3(3):163-170.
[7]Hantke,Braun V.Covalent binding of lipid to protein.Diglyceride and amide-linked fatty acid at the N-terminal end of the murein-lipoprotein of the Escherichia coli outer membrane[J].Eur J Biochem,1973,34(2):284-296.
[8]Driessen A J,Nouwen N.Protein translocation across thebacterial cytoplasmic membrane[J].Ann Rev Biochem,2008,77(1):643-667.
[9]Berks B C,Palmer T,Sargent F.Protein targeting by thebacterial twin-arginine translocation(Tat)pathway[J].Curr Opin Microbiol,2005,8(2):174-181.
[10]Guotao Mao,Yan Zhao,Xuejun Zhang,et al.Crystal structure of E.coli lipoprotein diacylglyceryl transferase[J].Nat Commun,2016,7:10198-10210.
[11]Hayashi S,Chang S Y,Chang S,et al.Modification and processing of internalized signal sequences of prolipoprotein in Escherichia coli and in Bacillus subtilis[J].J Biol Chem,1985,260(9):5753-5759
[12]Navarre W W,Daefler S,Schneewind O.Cell wall sorting of lipoproteins in Staphylococcus aureus[J].J Bacteriol,178,178(2):441-446.
[13]Babu M M,Priya M L,Selvan A T,et al.A database ofbacterial lipoproteins(DOLOP)with functionalassignments to predicted lipoproteins[J].J Bacteriol,2006,188(8):2761-2773.
[14]Gan K,Sankaran K,Williams M G,et al.The umpAgene of Escherichia coli encodes phosphatidylglycerol:Prolipoprotein diacylglyceryl transferase(lgt)and regulates thymidylate synthase levels through translational coupling[J].J Bacteriol,1995,177(7):1879-1882.
[15]Tokunaga M,Loranger J M,Wu H C.Prolipoprotein modificationand processing enzymes in Escherichia coli[J].J Biol Chem,1984,259(6):3825-3830.
[16]T h o m p s o n B J,Wi d d i c k D A,H i c k s M G,e t a l.Investigating lipoprotein biogenesis and function in the model Gram-positive bacterium Streptomyces coelicolor[J].Mol Microbiol,2010,77(4):943-957.
[17]Sankaran K,Wu H C.Lipid modification of bacterial prolipoprotein:Transfer of diacylglycerylmoiety from phosphatidylglycerol[J].J Biol Chem,1994,269(31):19701-19706.
[18]Pailler J,Aucher W,Pires M,et al.Phosphatidylglycerol:Prolipoproteindiacylglyceryltransferase(Lgt)of E.coli has seven transmembrane segments and its essentialresidues are embedded in the membrane[J].J Bacteriol,2012,194(9):2142-2151.
[19]Sankaran K,Gan K,Rash B,et al.Roles of histidine-103and tyrosine-235 in the function of the prelipoprotein diacylglyceryl transferase of Escherichia coli[J].J Bacteriol,1997,179(9):2944-2948.
[20]Malinverni J C,Werner J,Kim S,et al.YfiO stabilizes the YaeT complex and is essential for outer membrane protein assembly in Escherichia coli[J].Mol Microbiol,2006,61(1):151-164.
[21]Leskela S,Wahlstrom E,Kontinen V P,et al.Lipid modification of prelipoproteins isdispensable for growth but essential for efficient protein secretion in Bacillus subtilis:characterization of the Lgt gene[J].MolMicrobiol,1999,31(4):1075-1085.
[22]Tjalsma H,Kontinen V P,Pragai Z,et al.The role of lipoprotein processing by signal peptidase II in the Grampositive eubacterium Bacillus subtilis.Signal peptidase II is required for the efficient secretion of alpha-amylase,a nonlipoprotein[J].J Biol Chem,1999,274(3):1698-1707.
[23]Bengtsson J,Karamata D.Bacillus subtilis contains two small c-type cytochromes with homologous heme domains but different types of membrane anchors[J].J Biol Chem,1999,274(37):6179-26184.
[24]Igarashi T.Setlow B,Paidhungat M,et al.Effects of a gerF(lgt)mutation on the germination of spores of Bacillus subtilis[J].J Bacteriol,2004,186(10):2984-2991
[25]Brik A,Wong C H.HIV-1 protease:mechanism and drug discovery[J].Org Biomol Chem,2003,1(1):5-14.
[26]Gerstel B,Loessner M,Wehland J,et al.Inactivation of Lgt allows systematic characterization of lipoproteins from Listeria monocytogenes[J].J Bacteriol,2007,189(2):313-324.
[27]Henneke P,Dramsi S,Mancuso G,et al.Lipoproteins arecritical TLR2 activating toxins in group B streptococcal sepsis[J].J Immunol,2008,180(9):6149-6158.
[28]Denham E L,Ward P N,Leigh J A,et al.Lipoprotein signal peptides are processed by Lsp and Eep of Streptococcus uberis[J].J Bacteriol,2008,190(13):4641-4647.
[29]HamiltonA,Robinson C,Sutcliffeet I C,et al.Mutation of the maturase lipoprotein attenuates the virulence of Streptococcus equi to a greater extent than does loss of general lipoprotein lipidation[J].Infect Immun,2006,74(12):6907-6919.
[30]Remaut H,Fronze R.In bacterial membranes:Structural and molecular biology[J].Caister Academic Press,2014,(243):55-179.
[31]Zuckert W R.Protein trafficking and secretion in bacteria[J].Biochim Biophys Acta,2014,8(1843):1509-1516.
[32]Buddelmeijer N.The molecular mechanism of bacterial lipoprotein modification-how,when and why[J].FEMSMicrobio.Rev,2015,39(2):246-2619.
[33]Kovacs-Simon A,Titball R W,Michell S L.Lipoproteins of bacterial pathogens[J].Infect Immun,2011,79(2):548-561.
[34]Vogeley L,Bailey J,Stansfeld L,et al.Structural basis of lipoprotein signal peptidase II action and inhibition by the antibiotic globomycin[J].Science,2016,351(6275):876.
[35]Inukai M,Enokita R,Torikata A,et al.Globomycin,a new peptideantibiotic with spheroplast-forming activity.I.Taxonomy of producing organisms and fermentation[J].JAntibiot,1978,31(5):410-420.
[36]Dev I K,Harvey R J,Ray P H.Inhibition of prolipoprotein signal peptidase by globomycin[J].J Biol Chem,1985,260(10):5891-5984.
[37]Xiao Y,Wall D.Genetic redundancy,proximity,and functionality of lspA,the target of antibiotic TA,in the Myxococcus xanthus producer strain[J].J Bacteriol,2014,196(6):1174-1183.
[38]Kiho T,Nakayama M,Yasuda K,et al.Synthesis and antimicrobial activity of novel globomycin analogues[J].Bioorg Med Chem Lett,2003,13(14):2315-2318.
[39]Kiho T,Nakayama M,Yasuda K,et al.Structure-activity relationships of globomycin analogues as antibiotics[J].Bioorg Med Chem,2004,12(2):337-361.
[40]Rosenberg E,Dworkin M.Autocides and a paracide,antibiotic TA,produced by Myxococcus xanthus[J].J Ind Microbiol,1996,17(5-6):424-431.
[41]Seiya K,Anna O,Daniel W,et al.Lipoprotein signal peptidase inhibitors with antibiotic properties identified through design of a robust in vitro HT platform[J].Cell Chem Biol,2018,25(3):1-8.
[42]Gupta S D,Wu H C.Identification and subcellular localization of apolipoprotein N-acyltransferase in Escherichia coli[J].FEMS Microbiol Lett,1991,78(1):37-41.
[43]Fukuda A,Matsuyama S,Hara T,et al.Aminoacylation of the N-terminal cysteine is essential for Loldependentrelease of lipoproteins from membranes but does not depend on lipoproteinsorting signals[J].J Biol Chem,2002,277(45):43512-43518.
[44]Gupta S D,DowhamW,Wu H C.Phosphatidylethanolamine is not essential for the N-acylation of apolipoprotein in Escherichia coli[J].J Biol Chem,1991,266(15):9983-9986.
[45]Vidal-Ingigliardi D,Lewenza S,Buddelmeijer N.Identification of essential residues in apolipoprotein N-acyltransferase,a member of the CN hydrolase family[J].J Bacteriol,2007,189(12):4456-4464.
[46]Buddelmeijer N,Young R.The essential Escherichia coli apolipoprotein N-acyltransferase(Lnt)exists as an extracytoplasmic thioester acyl-enzyme intermediate[J].Biochemistry,2010,49(2):341-346.
[47]Hillmann F,Argentini M,Buddelmeijer N.Kinetics and phospholipid specificity of apolipoprotein N-acyltransferase[J].J Biol Chem,2011,286(32):27936-27946.
[48]Tschumi A,Nai C,Auchli Y,et al.Identification of apolipoprotein N-acyltransferase(Lnt)in mycobacteria[J].JBiol Chem,2009,284(40):27146-27156.
[49]Widdick D A,Hicks M G,Thompson B J,et al.Dissecting the complete lipoprotein biogenesis pathway in Streptomyces scabies[J].Mol Microbiol,2011,80(5):1395-1412.
[50]Goren M B.Mycobacterial lipids:selected topics[J].Bacteriol Rev,1972,36(1):33-64.
[51]Jackowski S,Rock C O.Transfer of fatty acids from the1-position of phosp-hatidylethanolamine to the major outer membrane lipoprotein of Escherichia coli[J].J Biol Chem,1986,261(24):11328-11333.
[52]Vidal-Ingigliardi D,Lewenza S,Buddelmeijer N.Identification of essential residues in apolipoprotein N-acyltransferase,a member of the CN hydrolase family[J].J Bacteriol,2007,189(12):4456-4464.
[53]Buddelmeijer N,Young R.The essential Escherichia coli apolipoprotein N-acyltransferase(Lnt)exists as an extra cytoplasmic thioester acyl-enzyme intermediate[J].Biochemistry,2010,49(2):341-346.
[54]Widdick D A,Hicks M G,Thompson B J,et al.Dissecting the complete lipoprotein biogenesis pathway in Streptomyces scabies[J].Mol Microbiol,2011,80(5):1395-1412.
[55]Cameron L N,Michele D,Jeremy M M,et al.Structural insights into lipoprotein N-acylation by Escherichia coli apolipoprotein N-acyltransferase[J].PNAS,2017,114(30):6044-6053.