1932

Abstract

Chris Raetz passed away on August 16, 2011, still at the height of his productive years. His seminal contributions to biomedical research were in the genetics, biochemistry, and structural biology of phospholipid and lipid A biosynthesis in and other gram-negative bacteria. He defined the catalytic properties and structures of many of the enzymes responsible for the “Raetz pathway for lipid A biosynthesis.” His deep understanding of chemistry, coupled with knowledge of medicine, biochemistry, genetics, and structural biology, formed the underpinnings for his contributions to the lipid field. He displayed an intense passion for science and a broad interest that came from a strong commitment to curiosity-driven research, a commitment he imparted to his mentees and colleagues. What follows is a testament to both Chris's science and humanity from his friends and colleagues.

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2013-06-02
2024-10-15
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Literature Cited

  1. Dowhan W. 1.  2011. The Raetz pathway for lipid A biosynthesis: Christian Rudolf Hubert Raetz, MD, PhD, 1946–2011. J. Lipid Res 52:1857–60 [Google Scholar]
  2. Raetz CR, Dowhan W, Kennedy EP. 2.  1976. Partial purification and characterization of cytidine 5′-diphosphate-diglyceride hydrolase from membranes of Escherichia coli. J. Bacteriol. 125:855–63 [Google Scholar]
  3. Raetz CR, Hirschberg CB, Dowhan W, Wickner WT, Kennedy EP. 3.  1972. A membrane-bound pyrophosphatase in Escherichia coli catalyzing the hydrolysis of cytidine diphosphate-diglyceride. J. Biol. Chem. 247:2245–47 [Google Scholar]
  4. Raetz CR, Kennedy EP. 4.  1972. The association of phosphatidylserine synthetase with ribosomes in extracts of Escherichia coli. J. Biol. Chem. 247:2008–14 [Google Scholar]
  5. Raetz CR, Kennedy EP. 5.  1973. Function of cytidine diphosphate-diglyceride and deoxycytidine diphosphate-diglyceride in the biogenesis of membrane lipids in Escherichia coli. J. Biol. Chem. 248:1098–105 [Google Scholar]
  6. Raetz CR, Kennedy EP. 6.  1974. Partial purification and properties of phosphatidylserine synthetase from Escherichia coli. J. Biol. Chem. 249:5038–45 [Google Scholar]
  7. Dowhan W, Wickner WT, Kennedy EP. 7.  1974. Purification and properties of phosphatidylserine decarboxylase from Escherichia coli. J. Biol. Chem. 249:3079–84 [Google Scholar]
  8. Raetz CR. 8.  1975. Isolation of Escherichia coli mutants defective in enzymes of membrane lipid synthesis. Proc. Natl. Acad. Sci. USA 72:2274–78 [Google Scholar]
  9. Esko JD, Wermuth MM, Raetz CR. 9.  1981. Thermolabile CDP-choline synthetase in an animal cell mutant defective in lecithin formation. J. Biol. Chem. 256:7388–93 [Google Scholar]
  10. Raetz CR, Larson TJ, Dowhan W. 10.  1977. Gene cloning for the isolation of enzymes of membrane lipid synthesis: phosphatidylserine synthase overproduction in Escherichia coli. Proc. Natl. Acad. Sci. USA 74:1412–16 [Google Scholar]
  11. Raetz CR. 11.  1986. Molecular genetics of membrane phospholipid synthesis. Annu. Rev. Genet. 20:253–95 [Google Scholar]
  12. Nishijima M, Bulawa CE, Raetz CR. 12.  1981. Two interacting mutations causing temperature-sensitive phosphatidylglycerol synthesis in Escherichia coli membranes. J. Bacteriol. 145:113–21 [Google Scholar]
  13. Nishijima M, Raetz CR. 13.  1979. Membrane lipid biogenesis in Escherichia coli: identification of genetic loci for phosphatidylglycerophosphate synthetase and construction of mutants lacking phosphatidylglycerol. J. Biol. Chem. 254:7837–44 [Google Scholar]
  14. Nishijima M, Raetz CR. 14.  1981. Characterization of two membrane-associated glycolipids from an Escherichia coli mutant deficient in phosphatidylglycerol. J. Biol. Chem. 256:10690–96 [Google Scholar]
  15. Onishi HR, Pelak BA, Gerckens LS, Silver LL, Kahan FM. 15.  et al. 1996. Antibacterial agents that inhibit lipid A biosynthesis. Science 274:980–82 [Google Scholar]
  16. Wickner WT, Stubbe J, Hirschberg CB, Garrett T, Dowhan W. 16.  2011. Chris Raetz, scientist and enduring friend. Proc. Natl. Acad. Sci. USA 108:17255–56 [Google Scholar]
  17. Stubbe J. 17.  2012. Christian R. Raetz (1946–2011). ACS Chem. Biol. 7:12–13 [Google Scholar]
  18. Rick PD, Fung LW, Ho C, Osborn MJ. 18.  1977. Lipid A mutants of Salmonella typhimurium. Purification and characterization of a lipid A precursor produced by a mutant in 3-deoxy-d-mannooctulosonate-8-phosphate synthetase. J. Biol. Chem. 252:4904–12 [Google Scholar]
  19. Qureshi N, Takayama K, Ribi E. 19.  1982. Purification and structural determination of nontoxic lipid A obtained from the lipopolysaccharide of Salmonella typhimurium. J. Biol. Chem. 257:11808–15 [Google Scholar]
  20. Takayama K, Qureshi N, Mascagni P, Anderson L, Raetz CR. 20.  1983. Glucosamine-derived phospholipids in Escherichia coli. Structure and chemical modification of a triacyl glucosamine 1-phosphate found in a phosphatidylglycerol-deficient mutant. J. Biol. Chem. 258:14245–52 [Google Scholar]
  21. Bulawa CE, Raetz CR. 21.  1984. The biosynthesis of Gram-negative endotoxin. Identification and function of UDP-2,3-diacylglucosamine in Escherichia coli. J. Biol. Chem. 259:4846–51 [Google Scholar]
  22. Ray BL, Painter G, Raetz CR. 22.  1984. The biosynthesis of Gram-negative endotoxin. Formation of lipid A disaccharides from monosaccharide precursors in extracts of Escherichia coli. J. Biol. Chem. 259:4852–59 [Google Scholar]
  23. Raetz CR, Purcell S, Meyer MV, Qureshi N, Takayama K. 23.  1985. Isolation and characterization of eight lipid A precursors from a 3-deoxy-d-manno-octylosonic acid-deficient mutant of Salmonella typhimurium. J. Biol. Chem. 260:16080–88 [Google Scholar]
  24. Raetz CR, Reynolds CM, Trent MS, Bishop RE. 24.  2007. Lipid A modification systems in gram-negative bacteria. Annu. Rev. Biochem. 76:295–329 [Google Scholar]
  25. Anderson MS, Bulawa CE, Raetz CR. 25.  1985. The biosynthesis of Gram-negative endotoxin. Formation of lipid A precursors from UDP-GlcNAc in extracts of Escherichia coli. J. Biol. Chem. 260:15536–41 [Google Scholar]
  26. Raetz CR, Roderick SL. 26.  1995. A left-handed parallel β helix in the structure of UDP-N-acetylglucosamine acyltransferase. Science 270:997–1000 [Google Scholar]
  27. Coggins BE, McClerren AL, Jiang L, Li X, Rudolph J. 27.  et al. 2005. Refined solution structure of the LpxC-TU-514 complex and pKa analysis of an active site histidine: insights into the mechanism and inhibitor design. Biochemistry 44:1114–26 [Google Scholar]
  28. Kamio Y, Nikaido H. 28.  1976. Outer membrane of Salmonella typhimurium: accessibility of phospholipid head groups to phospholipase c and cyanogen bromide activated dextran in the external medium. Biochemistry 15:2561–70 [Google Scholar]
  29. Hancock RE, Diamond G. 29.  2000. The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol. 8:402–10 [Google Scholar]
  30. Ernst RK, Guina T, Miller SI. 30.  2001. Salmonella typhimurium outer membrane remodeling: role in resistance to host innate immunity. Microbes Infect. 3:1327–34 [Google Scholar]
  31. Bader MW, Sanowar S, Daley ME, Schneider AR, Cho U. 31.  et al. 2005. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 122:461–72 [Google Scholar]
  32. Trent MS, Pabich W, Raetz CR, Miller SI. 32.  2001. A PhoP/PhoQ-induced lipase (PagL) that catalyzes 3-O-deacylation of lipid A precursors in membranes of Salmonella typhimurium. J. Biol. Chem. 276:9083–92 [Google Scholar]
  33. Gibbons HS, Lin S, Cotter RJ, Raetz CR. 33.  2000. Oxygen requirement for the biosynthesis of the S-2-hydroxymyristate moiety in Salmonella typhimurium lipid A. Function of LpxO, a new Fe2+/α-ketoglutarate-dependent dioxygenase homologue. J. Biol. Chem. 275:32940–49 [Google Scholar]
  34. Murata T, Tseng W, Guina T, Miller SI, Nikaido H. 34.  2007. PhoPQ-mediated regulation produces a more robust permeability barrier in the outer membrane of Salmonella enterica serovar Typhimurium. J. Bacteriol. 189:7213–22 [Google Scholar]
  35. Vorachek-Warren MK, Carty SM, Lin S, Cotter RJ, Raetz CR. 35.  2002. An Escherichia coli mutant lacking the cold shock-induced palmitoleoyltransferase of lipid A biosynthesis: absence of unsaturated acyl chains and antibiotic hypersensitivity at 12°C. J. Biol. Chem. 277:14186–93 [Google Scholar]
  36. Polissi A, Georgopoulos C. 36.  1996. Mutational analysis and properties of the msbA gene of Escherichia coli, coding for an essential ABC family transporter. Mol. Microbiol. 20:1221–33 [Google Scholar]
  37. Zhou Z, White KA, Polissi A, Georgopoulos C, Raetz CR. 37.  1998. Function of Escherichia coli MsbA, an essential ABC family transporter, in lipid A and phospholipid biosynthesis. J. Biol. Chem. 273:12466–75 [Google Scholar]
  38. Doerrler WT, Reedy MC, Raetz CR. 38.  2001. An Escherichia coli mutant defective in lipid export. J. Biol. Chem. 276:11461–64 [Google Scholar]
  39. Doerrler WT, Raetz CR. 39.  2002. ATPase activity of the MsbA lipid flippase of Escherichia coli. J. Biol. Chem. 277:36697–705 [Google Scholar]
  40. Golenbock DT, Hampton RY, Qureshi N, Takayama K, Raetz CR. 40.  1991. Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. J. Biol. Chem. 266:19490–98 [Google Scholar]
  41. Zagorski N. 41.  2007. Profile of Christian R. H. Raetz.. Proc. Natl. Acad. Sci. USA 104:17252–54 [Google Scholar]
  42. McClerren AL, Endsley S, Bowman JL, Andersen NH, Guan Z. 42.  et al. 2005. A slow, tight-binding inhibitor of the zinc-dependent deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin. Biochemistry 44:16574–83 [Google Scholar]
  43. Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE. 43.  1974. Steroid 5α-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 186:1213–15 [Google Scholar]
  44. Gormley GJ, Stoner E, Rittmaster RS, Gregg H, Thompson DL. 44.  et al. 1990. Effects of finasteride (MK-906), a 5α-reductase inhibitor, on circulating androgens in male volunteers. J. Clin. Endocrinol. Metab. 70:1136–41 [Google Scholar]
  45. Andersson S, Bishop RW, Russell DW. 45.  1989. Expression cloning and regulation of steroid 5α-reductase, an enzyme essential for male sexual differentiation. J. Biol. Chem. 264:16249–55 [Google Scholar]
  46. Andersson S, Berman DM, Jenkins EP, Russell DW. 46.  1991. Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism. Nature 354:159–61 [Google Scholar]
  47. Jenkins EP, Andersson S, Imperato-McGinley J, Wilson JD, Russell DW. 47.  1992. Genetic and pharmacological evidence for more than one human steroid 5α-reductase. J. Clin. Investig. 89:293–300 [Google Scholar]
  48. Russell DW, Wilson JD. 48.  1994. Steroid 5α-reductase: two genes/two enzymes. Annu. Rev. Biochem. 63:25–61 [Google Scholar]
  49. Harris G, Azzolina B, Baginsky W, Cimis G, Rasmusson GH. 49.  et al. 1992. Identification and selective inhibition of an isozyme of steroid 5α-reductase in human scalp. Proc. Natl. Acad. Sci. USA 89:10787–91 [Google Scholar]
  50. Price NP, Jeyaretnam B, Carlson RW, Kadrmas JL, Raetz CR, Brozek KA. 50.  1995. Lipid A biosynthesis in Rhizobium leguminosarum: role of a 2-keto-3-deoxyoctulosonate-activated 4′ phosphatase. Proc. Natl. Acad. Sci. USA 92:7352–56 [Google Scholar]
  51. Brozek KA, Kadrmas JL, Raetz CR. 51.  1996. Lipopolysaccharide biosynthesis in Rhizobium leguminosarum. Novel enzymes that process precursors containing 3-deoxy-d-manno-octulosonic acid. J. Biol. Chem. 271:32112–18 [Google Scholar]
  52. Kadrmas JL, Brozek KA, Raetz CR. 52.  1996. Lipopolysaccharide core glycosylation in Rhizobium leguminosarum. An unusual mannosyl transferase resembling the heptosyl transferase I of Escherichia coli. J. Biol. Chem. 271:32119–25 [Google Scholar]
  53. Chin DJ, Gil G, Russell DW, Liscum L, Luskey KL. 53.  et al. 1984. Nucleotide sequence of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, a glycoprotein of endoplasmic reticulum. Nature 308:613–17 [Google Scholar]
  54. Russell DW. 54.  2003. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72:137–74 [Google Scholar]
  55. Fahy E, Subramaniam S, Brown HA, Glass CK, Merrill AH Jr. 55.  et al. 2005. A comprehensive classification system for lipids. J. Lipid Res. 46:839–61 [Google Scholar]
  56. Sud M, Fahy E, Cotter D, Brown A, Dennis EA. 56.  et al. 2007. LMSD: LIPID MAPS structure database. Nucleic Acids Res. 35:D527–32 [Google Scholar]
  57. Raetz CR, Garrett TA, Reynolds CM, Shaw WA, Moore JD. 57.  et al. 2006. Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4. J. Lipid Res. 47:1097–111 [Google Scholar]
  58. Dennis EA, Deems RA, Harkewicz R, Quehenberger O, Brown HA. 58.  et al. 2010. A mouse macrophage lipidome. J. Biol. Chem. 285:39976–85 [Google Scholar]
  59. Quehenberger O, Armando AM, Brown AH, Milne SB, Myers DS. 59.  et al. 2010. Lipidomics reveals a remarkable diversity of lipids in human plasma. J. Lipid Res. 51:3299–305 [Google Scholar]
  60. Wang X, Karbarz MJ, McGrath SC, Cotter RJ, Raetz CR. 60.  2004. MsbA transporter-dependent lipid A 1-dephosphorylation on the periplasmic surface of the inner membrane: topography of Francisella novicida LpxE expressed in Escherichia coli. J. Biol. Chem. 279:49470–78 [Google Scholar]
  61. Kong Q, Six DA, Roland KL, Liu Q, Gu L. 61.  et al. 2011. Salmonella synthesizing 1-dephosphorylated [corrected] lipopolysaccharide exhibits low endotoxic activity while retaining its immunogenicity. J. Immunol. 187:412–23 [Google Scholar]
  62. Icho T, Raetz CR. 62.  1983. Multiple genes for membrane-bound phosphatases in Escherichia coli and their action on phospholipid precursors. J. Bacteriol. 153:722–30 [Google Scholar]
  63. Funk CR, Zimniak L, Dowhan W. 63.  1992. The pgpA and pgpB genes of Escherichia coli are not essential: evidence for a third phosphatidylglycerophosphate phosphatase. J. Bacteriol. 174:205–13 [Google Scholar]
  64. Lu YH, Guan Z, Zhao J, Raetz CR. 64.  2011. Three phosphatidylglycerol-phosphate phosphatases in the inner membrane of Escherichia coli. J. Biol. Chem. 286:5506–18 [Google Scholar]
  65. Zhang J, Guan Z, Murphy AN, Wiley SE, Perkins GA. 65.  et al. 2011. Mitochondrial phosphatase PTPMT1 is essential for cardiolipin biosynthesis. Cell Metab. 13:690–700 [Google Scholar]
  66. Pagliarini DJ, Wiley SE, Kimple ME, Dixon JR, Kelly P. 66.  et al. 2005. Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic β cells. Mol. Cell 19:197–207 [Google Scholar]
  67. Pluschke G, Hirota Y, Overath P. 67.  1978. Function of phospholipids in Escherichia coli. Characterization of a mutant deficient in cardiolipin synthesis. J. Biol. Chem. 253:5048–55 [Google Scholar]
  68. Hiraoka S, Nukui K, Uetake N, Ohta A, Shibuya I. 68.  1991. Amplification and substantial purification of cardiolipin synthase of Escherichia coli. J. Biochem. 110:443–49 [Google Scholar]
  69. Guo D, Tropp BE. 69.  2000. A second Escherichia coli protein with CL synthase activity. Biochim. Biophys. Acta 1483:263–74 [Google Scholar]
  70. Tan BK, Bogdanov M, Zhao J, Dowhan W, Raetz CRH, Guan Z. 70.  2012. Discovery of a novel cardiolipin synthase in Escherichia coli utilizing phosphatidylethanolamine and phosphatidylglycerol as substrates. Proc. Natl. Acad. Sci. USA 109:16504–9 [Google Scholar]
  71. Li C, Guan Z, Liu D, Raetz CR. 71.  2011. Pathway for lipid A biosynthesis in Arabidopsis thaliana resembling that of Escherichia coli. Proc. Natl. Acad. Sci. USA 108:11387–92 [Google Scholar]
  72. Sun W, Six D, Kuang X, Roland KL, Raetz CR, Curtiss R 3rd. 72.  2011. A live attenuated strain of Yersinia pestis KIM as a vaccine against plague. Vaccine 29:2986–98 [Google Scholar]
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