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Microbiol Mol Biol Rev. Dec 1997; 61(4): 429–441.
PMCID: PMC232619

Cyclopropane ring formation in membrane lipids of bacteria.

Abstract

It has been known for several decades that cyclopropane fatty acids (CFAs) occur in the phospholipids of many species of bacteria. CFAs are formed by the addition of a methylene group, derived from the methyl group of S-adenosylmethionine, across the carbon-carbon double bond of unsaturated fatty acids (UFAs). The C1 transfer does not involve free fatty acids or intermediates of phospholipid biosynthesis but, rather, mature phospholipid molecules already incorporated into membrane bilayers. Furthermore, CFAs are typically produced at the onset of the stationary phase in bacterial cultures. CFA formation can thus be considered a conditional, postsynthetic modification of bacterial membrane lipid bilayers. This modification is noteworthy in several respects. It is catalyzed by a soluble enzyme, although one of the substrates, the UFA double bond, is normally sequestered deep within the hydrophobic interior of the phospholipid bilayer. The enzyme, CFA synthase, discriminates between phospholipid vesicles containing only saturated fatty acids and those containing UFAs; it exhibits no affinity for vesicles of the former composition. These and other properties imply that topologically novel protein-lipid interactions occur in the biosynthesis of CFAs. The timing and extent of the UFA-to-CFA conversion in batch cultures and the widespread distribution of CFA synthesis among bacteria would seem to suggest an important physiological role for this phenomenon, yet its rationale remains unclear despite experimental tests of a variety of hypotheses. Manipulation of the CFA synthase of Escherichia coli by genetic methods has nevertheless provided valuable insight into the physiology of CFA formation. It has identified the CFA synthase gene as one of several rpoS-regulated genes of E. coli and has provided for the construction of strains in which proposed cellular functions of CFAs can be properly evaluated. Cloning and manipulation of the CFA synthase structural gene have also enabled this novel but extremely unstable enzyme to be purified and analyzed in molecular terms and have led to the identification of mechanistically related enzymes in clinically important bacterial pathogens.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Akamatsu Y, Law JH. Enzymatic synthesis of 10-methylene stearic acid and tuberculostearic acid. Biochem Biophys Res Commun. 1968 Oct 10;33(1):172–176. [PubMed]
  • Akamatsu Y, Law JH. Enzymatic alkylenation of phospholipid fatty acid chains by extracts of Mycobacterium phlei. J Biol Chem. 1970 Feb 25;245(4):701–708. [PubMed]
  • Beach DH, Pascal RA, Jr, Holz GG., Jr Effects of thiastearic acids on growth and on dihydrosterculic acid and other phospholipid fatty acyl groups of Leishmania promastigotes. Mol Biochem Parasitol. 1989 Jun 1;35(1):57–66. [PubMed]
  • Casadaban MJ, Martinez-Arias A, Shapira SK, Chou J. Beta-galactosidase gene fusions for analyzing gene expression in escherichia coli and yeast. Methods Enzymol. 1983;100:293–308. [PubMed]
  • Cheng X. Structure and function of DNA methyltransferases. Annu Rev Biophys Biomol Struct. 1995;24:293–318. [PubMed]
  • Cheng X, Blumenthal RM. Finding a basis for flipping bases. Structure. 1996 Jun 15;4(6):639–645. [PubMed]
  • Conrad RS, Gilleland HE., Jr Lipid alterations in cell envelopes of polymyxin-resistant Pseudomonas aeruginosa isolates. J Bacteriol. 1981 Nov;148(2):487–497. [PMC free article] [PubMed]
  • Cronan JE, Jr, Nunn WD, Batchelor JG. Studies on the biosynthesis of cyclopropane fatty acids in Escherichia coli. Biochim Biophys Acta. 1974 Apr 26;348(1):63–75. [PubMed]
  • Cronan JE, Jr, Reed R, Taylor FR, Jackson MB. Properties and biosynthesis of cyclopropane fatty acids in Escherichia coli. J Bacteriol. 1979 Apr;138(1):118–121. [PMC free article] [PubMed]
  • Crowfoot PD, Hunt AL. The effect of oxygen tension on methylene hexadecanoic acid formation in Pseudomonas fluorescens and Escherichia coli. Biochim Biophys Acta. 1970 May 5;202(3):550–552. [PubMed]
  • DeVeaux LC, Cronan JE, Jr, Smith TL. Genetic and biochemical characterization of a mutation (fatA) that allows trans unsaturated fatty acids to replace the essential cis unsaturated fatty acids of Escherichia coli. J Bacteriol. 1989 Mar;171(3):1562–1568. [PMC free article] [PubMed]
  • Díaz-Guerra L, Moreno F, San Millán JL. appR gene product activates transcription of microcin C7 plasmid genes. J Bacteriol. 1989 May;171(5):2906–2908. [PMC free article] [PubMed]
  • Dougherty DA. Cation-pi interactions in chemistry and biology: a new view of benzene, Phe, Tyr, and Trp. Science. 1996 Jan 12;271(5246):163–168. [PubMed]
  • Dubnau E, Lanéelle MA, Soares S, Bénichou A, Vaz T, Promé D, Promé JC, Daffé M, Quémard A. Mycobacterium bovis BCG genes involved in the biosynthesis of cyclopropyl keto- and hydroxy-mycolic acids. Mol Microbiol. 1997 Jan;23(2):313–322. [PubMed]
  • Dufourc EJ, Smith IC, Jarrell HC. A 2H-NMR analysis of dihydrosterculoyl-containing lipids in model membranes: structural effects of a cyclopropane ring. Chem Phys Lipids. 1983 Aug;33(2):153–177. [PubMed]
  • Eberhardt S, Richter G, Gimbel W, Werner T, Bacher A. Cloning, sequencing, mapping and hyperexpression of the ribC gene coding for riboflavin synthase of Escherichia coli. Eur J Biochem. 1996 Dec 15;242(3):712–719. [PubMed]
  • Fish WR, Holz GG, Jr, Beach DH, Owen E, Anekwe GE. The cyclopropane fatty acid of trypanosomatids. Mol Biochem Parasitol. 1981 Jun;3(2):103–115. [PubMed]
  • Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty BA, Merrick JM, et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995 Jul 28;269(5223):496–512. [PubMed]
  • George KM, Yuan Y, Sherman DR, Barry CE., 3rd The biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Identification and functional analysis of CMAS-2. J Biol Chem. 1995 Nov 10;270(45):27292–27298. [PubMed]
  • Gitter B, Diefenbach R, Keweloh H, Riesenberg D. Influence of stringent and relaxed response on excretion of recombinant proteins and fatty acid composition in Escherichia coli. Appl Microbiol Biotechnol. 1995 Apr;43(1):89–92. [PubMed]
  • Gottesman S. Proteases and their targets in Escherichia coli. Annu Rev Genet. 1996;30:465–506. [PubMed]
  • Grogan DW, Cronan JE., Jr Use of lambda phasmids for deletion mapping of non-selectable markers cloned in plasmids. Gene. 1983 Apr;22(1):75–83. [PubMed]
  • Grogan DW, Cronan JE., Jr Cloning and manipulation of the Escherichia coli cyclopropane fatty acid synthase gene: physiological aspects of enzyme overproduction. J Bacteriol. 1984 Apr;158(1):286–295. [PMC free article] [PubMed]
  • Grogan DW, Cronan JE., Jr Genetic characterization of the Escherichia coli cyclopropane fatty acid (cfa) locus and neighboring loci. Mol Gen Genet. 1984;196(2):367–372. [PubMed]
  • Grogan DW, Cronan JE., Jr Characterization of Escherichia coli mutants completely defective in synthesis of cyclopropane fatty acids. J Bacteriol. 1986 Jun;166(3):872–877. [PMC free article] [PubMed]
  • Guckert JB, Hood MA, White DC. Phospholipid ester-linked fatty acid profile changes during nutrient deprivation of Vibrio cholerae: increases in the trans/cis ratio and proportions of cyclopropyl fatty acids. Appl Environ Microbiol. 1986 Oct;52(4):794–801. [PMC free article] [PubMed]
  • Halper LA, Norton SJ. Regulation of cyclopropane fatty acid biosynthesis by variations in enzyme activities. Biochem Biophys Res Commun. 1975 Feb 3;62(3):683–688. [PubMed]
  • Harley JB, Santangelo GM, Rasmussen H, Goldfine H. Dependence of Escherichia coli hyperbaric oxygen toxicity on the lipid acyl chain composition. J Bacteriol. 1978 Jun;134(3):808–820. [PMC free article] [PubMed]
  • Haque M, Hirai Y, Yokota K, Mori N, Jahan I, Ito H, Hotta H, Yano I, Kanemasa Y, Oguma K. Lipid profile of Helicobacter spp.: presence of cholesteryl glucoside as a characteristic feature. J Bacteriol. 1996 Apr;178(7):2065–2070. [PMC free article] [PubMed]
  • Heipieper HJ, de Bont JA. Adaptation of Pseudomonas putida S12 to ethanol and toluene at the level of fatty acid composition of membranes. Appl Environ Microbiol. 1994 Dec;60(12):4440–4444. [PMC free article] [PubMed]
  • HILDEBRAND JG, LAW JH. FATTY ACID DISTRIBUTION IN BACTERIAL PHOSPHOLIPIDS. THE SPECIFICITY OF THE CYCLOPROPANE SYNTHETASE REACTION. Biochemistry. 1964 Sep;3:1304–1308. [PubMed]
  • Inamoto Y, Hamanaka S, Hamanaka Y, Nagate T, Kondo I, Takemoto T, Okita K. Lipid composition and fatty acid analysis of Helicobacter pylori. J Gastroenterol. 1995 Jun;30(3):315–318. [PubMed]
  • Jacques NA, Hunt A l. Studies on cyclopropane fatty acid synthesis. Effect of carbon source and oxygen tension on cyclopropane fatty acid synthetase activity in Pseudomonas denitrificans. Biochim Biophys Acta. 1980 Sep 8;619(3):453–470. [PubMed]
  • Jacques NA. Relationship between cyclopropane synthetase and the formation of cyclopropane fatty acids by Proteus vulgaris grown under various respiratory conditions. J Gen Microbiol. 1982 Jan;128(1):177–184. [PubMed]
  • Jishage M, Ishihama A. Variation in RNA polymerase sigma subunit composition within different stocks of Escherichia coli W3110. J Bacteriol. 1997 Feb;179(3):959–963. [PMC free article] [PubMed]
  • Jungkind DL, Wood RC. Factors involved in the synthesis of cyclopropane fatty acids by Streptococcus faecalis. Biochim Biophys Acta. 1974 Feb 25;337(2):286–297. [PubMed]
  • Kagan RM, Clarke S. Widespread occurrence of three sequence motifs in diverse S-adenosylmethionine-dependent methyltransferases suggests a common structure for these enzymes. Arch Biochem Biophys. 1994 May 1;310(2):417–427. [PubMed]
  • Keweloh H, Heipieper HJ. Trans unsaturated fatty acids in bacteria. Lipids. 1996 Feb;31(2):129–137. [PubMed]
  • Knivett VA, Cullen J. Some factors affecting cyclopropane acid formation in Escherichia coli. Biochem J. 1965 Sep;96(3):771–776. [PMC free article] [PubMed]
  • Lange R, Fischer D, Hengge-Aronis R. Identification of transcriptional start sites and the role of ppGpp in the expression of rpoS, the structural gene for the sigma S subunit of RNA polymerase in Escherichia coli. J Bacteriol. 1995 Aug;177(16):4676–4680. [PMC free article] [PubMed]
  • Langley KE, Hawrot E, Kennedy EP. Membrane assembly: movement of phosphatidylserine between the cytoplasmic and outer membranes of Escherichia coli. J Bacteriol. 1982 Dec;152(3):1033–1041. [PMC free article] [PubMed]
  • Liu J, Barry CE, 3rd, Besra GS, Nikaido H. Mycolic acid structure determines the fluidity of the mycobacterial cell wall. J Biol Chem. 1996 Nov 22;271(47):29545–29551. [PubMed]
  • Macdonald PM, Sykes BD, McElhaney RN. Fluorine-19 nuclear magnetic resonance studies of lipid fatty acyl chain order and dynamics in Acholeplasma laidlawii B membranes. A direct comparison of the effects of cis and trans cyclopropane ring and double-bond substituents on orientational order. Biochemistry. 1985 Aug 13;24(17):4651–4659. [PubMed]
  • Marinari LA, Goldfine H, Panos C. Specificity of cyclopropane fatty acid synthesis in Escherichia coli. Utilization of isomers of monounsaturated fatty acids. Biochemistry. 1974 Apr 23;13(9):1978–1983. [PubMed]
  • McGarrity JT, Armstrong JB. The effect of temperature and other growth conditions on the fatty acid composition of Escherichia coli. Can J Microbiol. 1981 Aug;27(8):835–840. [PubMed]
  • McGarrity JT, Armstrong JB. Phase transition behaviour of artificial liposomes composed of phosphatidylcholines acylated with cyclopropane fatty acids. Biochim Biophys Acta. 1981 Jan 22;640(2):544–548. [PubMed]
  • Meyer H, Holz GG., Jr Biosynthesis of lipids by kinetoplastid flagellates. J Biol Chem. 1966 Nov 10;241(21):5000–5007. [PubMed]
  • Murakami-Murofushi K, Kobayashi S, Onimura K, Matsumoto M, Shioda M, Yoshida S, Shoji M, Murofushi H. Selective inhibition of DNA polymerase-alpha family with chemically synthesized derivatives of PHYLPA, a unique Physarum lysophosphatidic acid. Biochim Biophys Acta. 1995 Aug 24;1258(1):57–60. [PubMed]
  • Nieboer M, Vis AJ, Witholt B. Overproduction of a foreign membrane protein in Escherichia coli stimulates and depends on phospholipid synthesis. Eur J Biochem. 1996 Oct 15;241(2):691–696. [PubMed]
  • Nikaido H, Kim SH, Rosenberg EY. Physical organization of lipids in the cell wall of Mycobacterium chelonae. Mol Microbiol. 1993 Jun;8(6):1025–1030. [PubMed]
  • Ohlrogge JB, Gunstone FD, Ismail IA, Lands WE. Positional specificity of cyclopropane ring formation from cis-octadecenoic acid isomers in Escherichia coli. Biochim Biophys Acta. 1976 May 27;431(2):257–267. [PubMed]
  • Okuyama H, Okajima N, Sasaki S, Higashi S, Murata N. The cis/trans isomerization of the double bond of a fatty acid as a strategy for adaptation to changes in ambient temperature in the psychrophilic bacterium, Vibrio sp. strain ABE-1. Biochim Biophys Acta. 1991 Jun 19;1084(1):13–20. [PubMed]
  • Orgambide GG, Reusch RN, Dazzo FB. Methoxylated fatty acids reported in Rhizobium isolates arise from chemical alterations of common fatty acids upon acid-catalyzed transesterification procedures. J Bacteriol. 1993 Aug;175(15):4922–4926. [PMC free article] [PubMed]
  • Perly B, Smith IC, Jarrell HC. Effects of replacement of a double bond by a cyclopropane ring in phosphatidylethanolamines: a 2H NMR study of phase transitions and molecular organization. Biochemistry. 1985 Feb 12;24(4):1055–1063. [PubMed]
  • Polacheck JW, Tropp BE, Law JH. Biosynthesis of cyclopropane compounds. 8. The conversion of oleate to dihydrosterculate. J Biol Chem. 1966 Jul 25;241(14):3362–3364. [PubMed]
  • Pratt LA, Silhavy TJ. The response regulator SprE controls the stability of RpoS. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2488–2492. [PMC free article] [PubMed]
  • Rahman MD, Ziering DL, Mannarelli SJ, Swartz KL, Huang DS, Pascal RA., Jr Effects of sulfur-containing analogues of stearic acid on growth and fatty acid biosynthesis in the protozoan Crithidia fasciculata. J Med Chem. 1988 Aug;31(8):1656–1659. [PubMed]
  • Ramos JL, Duque E, Rodríguez-Herva JJ, Godoy P, Haïdour A, Reyes F, Fernández-Barrero A. Mechanisms for solvent tolerance in bacteria. J Biol Chem. 1997 Feb 14;272(7):3887–3890. [PubMed]
  • Roberts RJ. On base flipping. Cell. 1995 Jul 14;82(1):9–12. [PubMed]
  • Schluckebier G, O'Gara M, Saenger W, Cheng X. Universal catalytic domain structure of AdoMet-dependent methyltransferases. J Mol Biol. 1995 Mar 17;247(1):16–20. [PubMed]
  • Silbert DF, Ulbright TM, Honegger JL. Utilization of exogenous fatty acids for complex lipid biosynthesis and its effect on de novo fatty acid formation in Escherichia coli K-12. Biochemistry. 1973 Jan 2;12(1):164–171. [PubMed]
  • Smith DD, Jr, Norton SJ. Inhibition of cyclopropane fatty acid synthase by sinefungin and A9145C. Biochem Biophys Res Commun. 1980 Jun 30;94(4):1458–1462. [PubMed]
  • Su CJ, Reusch R, Sadoff HL. Fatty acids in phospholipids of cells, cysts, and germinating cysts of Azotobacter vinelandii. J Bacteriol. 1979 Mar;137(3):1434–1436. [PMC free article] [PubMed]
  • Taguchi M, Izui K, Katsuki H. Augmentation of cyclopropane fatty acid synthesis under stringent control in Escherichia coli. J Biochem. 1980 Dec;88(6):1879–1882. [PubMed]
  • Taylor F, Cronan JE., Jr Selection and properties of Escherichia coli mutants defective in the synthesis of cyclopropane fatty acids. J Bacteriol. 1976 Feb;125(2):518–523. [PMC free article] [PubMed]
  • Taylor FR, Cronan JE., Jr Cyclopropane fatty acid synthase of Escherichia coli. Stabilization, purification, and interaction with phospholipid vesicles. Biochemistry. 1979 Jul 24;18(15):3292–3300. [PubMed]
  • Taylor FR, Grogan DW, Cronan JE., Jr Cyclopropane fatty acid synthase from Escherichia coli. Methods Enzymol. 1981;71(Pt 100):133–139. [PubMed]
  • Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, Ketchum KA, Klenk HP, Gill S, Dougherty BA, et al. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature. 1997 Aug 7;388(6642):539–547. [PubMed]
  • Umbarger HE. Amino acid biosynthesis and its regulation. Annu Rev Biochem. 1978;47:532–606. [PubMed]
  • Wang AY, Grogan DW, Cronan JE., Jr Cyclopropane fatty acid synthase of Escherichia coli: deduced amino acid sequence, purification, and studies of the enzyme active site. Biochemistry. 1992 Nov 17;31(45):11020–11028. [PubMed]
  • Wang AY, Cronan JE., Jr The growth phase-dependent synthesis of cyclopropane fatty acids in Escherichia coli is the result of an RpoS(KatF)-dependent promoter plus enzyme instability. Mol Microbiol. 1994 Mar;11(6):1009–1017. [PubMed]
  • Weber FJ, Isken S, de Bont JA. Cis/trans isomerization of fatty acids as a defence mechanism of Pseudomonas putida strains to toxic concentrations of toluene. Microbiology. 1994 Aug;140(Pt 8):2013–2017. [PubMed]
  • Yuan Y, Barry CE., 3rd A common mechanism for the biosynthesis of methoxy and cyclopropyl mycolic acids in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12828–12833. [PMC free article] [PubMed]
  • Yuan Y, Crane DC, Musser JM, Sreevatsan S, Barry CE., 3rd MMAS-1, the branch point between cis- and trans-cyclopropane-containing oxygenated mycolates in Mycobacterium tuberculosis. J Biol Chem. 1997 Apr 11;272(15):10041–10049. [PubMed]
  • Yuan Y, Lee RE, Besra GS, Belisle JT, Barry CE., 3rd Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6630–6634. [PMC free article] [PubMed]
  • ZALKIN H, LAW JH, GOLDFINE H. Enzymatic synthesis of cyclopropane fatty acids catalyzed by bacterial extracts. J Biol Chem. 1963 Apr;238:1242–1248. [PubMed]
  • Zambrano MM, Siegele DA, Almirón M, Tormo A, Kolter R. Microbial competition: Escherichia coli mutants that take over stationary phase cultures. Science. 1993 Mar 19;259(5102):1757–1760. [PubMed]

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