New Aspects on Lanosterol 14α-Demethylase and Cytochrome P450 Evolution: Lanosterol/Cycloartenol Diversification and Lateral Transfer Authors
Received: 21 August 2003 Accepted: 12 January 2004 DOI:
Cite this article as: Režen, T., Debeljak, N., Kordiš, D. et al. J Mol Evol (2004) 59: 51. doi:10.1007/s00239-004-2603-1 Abstract.
Sterol 14α-demethylase (CYP51) is a member of the cytochrome P450 superfamily, widely found in animals, fungi, and plants but present in few prokaryotic groups. CYP51 is currently believed to be the ancestral cytochrome P450 that has been transferred from prokaryotes to eukaryotic kingdoms. We propose an alternate view of CYP51 evolution that has an impact on understanding the evolution of the entire CYP superfamily. Two hundred forty-nine bacterial and four archaeal CYP sequences have been aligned and a bacterial CYP tree designed, showing a separation of two branches. Prokaryotic CYP51s cluster to the minor branch, together with other eukaryote-like CYPs. Mycobacterial and methylococcal CYP51s cluster together (100% bootstrap probability), while
Streptomyces CYP51 remains on a distant branch. A CYP51 phylogenetic tree has been constructed from 44 sequences resulting in a ((plant, bacteria),(animal, fungi)) topology (100% bootstrap probability). This is in accordance with the lanosterol/cycloartenol diversification of sterol biosynthesis. The lanosterol branch (nonphotosynthetic lineage) follows the previously proposed topology of animal and fungal orthologues (100% bootstrap probability), while plant and D. discoideum CYP51s belong to the cycloartenol branch (photosynthetic lineage), all in accordance with biochemical data. Bacterial CYP51s cluster within the cycloartenol branch (69% bootstrap probability), which is indicative of a lateral gene transfer of a plant CYP51 to the methylococcal/mycobacterial progenitor, suggesting further that bacterial CYP51s are not the oldest CYP genes. Lateral gene transfer is likely far more important than hitherto thought in the development of the diversified CYP superfamily. Consequently, bacterial CYPs may represent a mixture of genes with prokaryotic and eukaryotic origin. Keywords Sterol biosynthesis CYP51 Lanosterol 14α-demethylase Cytochrome P450 Bacteria Mycobacterium tuberculosis References Anandatheerthavarada, HK, Amuthan, G, Biswas, G, Robin, MA, Murali, R, Waterman, MR, Avadhani, NG 2001 Evolutionarily divergent electron donor proteins interact with P450MT2 through the same helical domain but different contact points EMBO J 20 2394 2403 CrossRef PubMed Aoyama, Y, Noshiro, M, Gotoh, O, Imaoka, S, Funae, Y, Kurosawa, N, Horiuchi, T, Yoshida, Y 1996 Sterol 14-demethylase P450 (P45014DM*) is one of the most ancient and conserved P450 species J Biochem (Tokyo) 119 926 933 Aoyama, Y, Horiuchi, T, Gotoh, O, Noshiro, M, Yoshida, Y 1998 CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to eukaryotic CYP51 J Biochem (Tokyo) 124 694 696 Bellamine, A, Mangla, AT, Nes, WD, Waterman, MR 1999 Characterization and catalytic properties of the sterol 14alpha- demethylase from Mycobacterium tuberculosis Proc Natl Acad Sci USA 96 8937 8942 CrossRef PubMed Bellamine, A, Mangla, AT, Dennis, AL, Nes, WD, Waterman, MR 2001 Structural requirements for substrate recognition of Mycobacterium tuberculosis 14 alpha-demethylase: Implications for sterol biosynthesis J Lipid Res 42 128 136 PubMed Bloch, KE 1979 Speculations on the evolution of sterol structure and function CRC Crit Rev Biochem 7 1 5 PubMed Bode, HB, Zeggel, B, Silakowski, B, Wenzel, SC, Reichenbach, H, Muller, R 2003 Steroid biosynthesis in prokaryotes: identification of myxobacterial steroids and cloning of the first bacterial 2,3(S)-oxidosqualene cyclase from the myxobacterium Stigmatella aurantiaca Mol Microbiol 47 471 481 CrossRef PubMed Boucher, Y, Doolittle, WF 2000 The role of lateral gene transfer in the evolution of isoprenoid biosynthesis pathways Mol Microbiol 37 703 716 CrossRef PubMed Cavalier-Smith, T 2002 The neomuran origin of archaebacteria, the negibacterial root of the universal tree and bacterial megaclassification Int J Syst Evol Microbiol 52 7 76 PubMed Cole, ST, Brosch, R, Parkhill, J, Garnier, T, Churcher, C, Harris, D, Gordon, SV, Eiglmeier, K, Gas, S, Barry, CE, 3rd, , Tekaia, F, Badcock, K, Basham, D, Brown, D, Chillingworth, T, Connor, R, Davies, R, Devlin, K, Feltwell, T, Gentles, S, Hamlin, N, Holroyd, S, Hornsby, T, Jagels, K, Barrell, BG, et al. 1998 Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence Nature 393 537 544 CrossRef PubMed Debeljak, N, Fink, M, Rozman, D 2003 Many facets of mammalian lanosterol 14alpha-demethylase from the evolutionarily conserved cytochrome P450 family CYP51 Arch Biochem Biophys 409 159 171 CrossRef PubMed Degtyarenko, KN, Archakov, AI 1993 Molecular evolution of P450 superfamily and P450-containing monooxygenase systems FEBS Lett 332 1 8 CrossRef PubMed Gamieldien, J, Ptitsyn, A, Hide, W 2002 Eukaryotic genes in Mycobacterium tuberculosis could have a role in pathogenesis and immunomodulation Trends Genet 18 5 8 CrossRef PubMed Gatfield, J, Pieters, J 2000 Essential role for cholesterol in entry of mycobacteria into macrophages Science 288 1647 1650 CrossRef PubMed Gogarten, JP, Doolittle, WF, Lawrence, JG 2002 Prokaryotic evolution in light of gene transfer Mol Biol Evol 19 2226 2238 PubMed Jackson, CJ, Lamb, DC, Marczylo, TH, Warrilow, AG, Manning, NJ, Lowe, DJ, Kelly, DE, Kelly, SL 2002 A novel sterol 14alpha-demethylase/ferredoxin fusion protein (MCCYP51FX) from Methylococcus capsulatus represents a new class of the cytochrome P450 superfamily J Biol Chem 277 46959 46965 CrossRef PubMed Jackson, CJ, Lamb, DC, Marczylo, TH, Parker, JE, Manning, NL, Kelly, DE, Kelly, SL 2003 Conservation and cloning of CYP51: A sterol 14alpha-demethylase from Mycobacterium smegmatis Biochem Biophys Res Commun 301 558 563 CrossRef PubMed Jahnke, LL 1992 The effects of growth temperature on the methyl sterol and phospholipid fatty acid composition of Methylococcus capsulatus (Bath) FEMS Microbiol Lett 93 209 212 CrossRef PubMed Joubert, BM, Nguyen, LN, Matsuda, SP, Buckner, FS 2001 Cloning and functional characterization of a Trypanosoma brucei lanosterol 14alpha-demethylase gene Mol Biochem Parasitol 117 115 117 CrossRef PubMed Karlin, S 2001 Detecting anomalous gene clusters and pathogenicity islands in diverse bacterial genomes Trends Microbiol 9 335 343 CrossRef PubMed Lamb, DC, Kelly, DE, Kelly, SL 1998 Molecular diversity of sterol 14alpha-demethylase substrates in plants, fungi and humans FEBS Lett 425 263 265 CrossRef PubMed Lamb, DC, Fowler, K, Kieser, T, Manning, N, Podust, LM, Waterman, MR, Kelly, DE, Kelly, SL 2002a Sterol 14alpha-demethylase activity in Streptomyces coelicolor A3(2) is associated with an unusual member of the CYP51 gene family Biochem J 364 555 562 CrossRef Lamb, DC, Skaug, T, Song, HL, Jackson, CJ, Podust, LM, Waterman, MR, Kell, DB, Kelly, DE, Kelly, SL 2002b The cytochrome P450 complement (CYPome) of Streptomyces coelicolor A3(2) J Biol Chem 277 24000 24005 CrossRef Lamb, DC, Ikeda, H, Nelson, DR, Ishikawa, J, Skaug, T, Jackson, C, Omura, S, Waterman, MR, Kelly, SL 2003 Cytochrome P450 complement of avermectin-producer Streptomyces avermitilis and comparison to that of Streptomyces coelicolor A3(2) Biochem Biophys Res Commun 307 610 619 CrossRef PubMed Lepesheva, GI, Podust, LM, Bellamine, A, Waterman, MR 2001 Folding requirements are different between sterol 14alpha-demethylase (CYP51) from Mycobacterium tuberculosis and human or fungal orthologs J Biol Chem 276 28413 28420 CrossRef PubMed Liendo, A, Visbal, G, Piras, MM, Piras, R, Urbina, JA 1999 Sterol composition and biosynthesis in Trypanosoma cruzi amastigotes Mol Biochem Parasitol 104 81 91 CrossRef PubMed McLean, KJ, Scrutton, NS, Munro, AW 2003 Kinetic, spectroscopic and thermodynamic characterization of the Mycobacterium tuberculosis adrenodoxn reductase homologue FprA Biochem J 372 317 327 CrossRef PubMed Nelson, DR 1998 Metazoan cytochrome P450 evolution Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 121 15 22 CrossRef PubMed Nelson, DR 1999 Cytochrome P450 and the individuality of species Arch Biochem Biophys 369 1 10 CrossRef PubMed Nes, WD, Norton, RA, Crumley, FG, Madigan, SJ, Katz, ER 1990 Sterol phylogenesis and algal evolution Proc Natl Acad Sci USA 87 7565 7569 PubMed Ochman, H, Lawrence, JG, Groisman, EA 2000 Lateral gene transfer and the nature of bacterial innovation Nature 405 299 304 CrossRef PubMed Thompson, JD, Higgins, DG, Gibson, TJ 1994 CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice Nucleic Acids Res 22 4673 4680 PubMed Tizard, M, Bull, T, Millar, D, Doran, T, Martin, H, Sumar, N, Ford, J, Hermon-Taylor, J 1998 A low G+C content genetic island in Mycobacterium avium subsp. paratuberculosis and M. avium subsp. silvaticum with homologous genes in Mycobacterium tuberculosis Microbiology 144 3413 3423 PubMed Peer, Y, Wachter, R 1997 Construction of evolutionary distance trees with TREECON for Windows: Accounting for variation in nucleotide substitution rate among sites Comput Appl Biosci 13 227 230 PubMed Volkman, K 2003 Sterols in microorganisms Appl Microbiol Biotechnol 60 495 506 PubMed Wilding, EI, Brown, JR, Bryant, AP, Chalker, AF, Holmes, DJ, Ingraham, KA, Iordanescu, S, So, CY, Rosenberg, M, Gwynn, MN 2000 Identification, evolution, and essentiality of the mevalonate pathway for isopentenyl diphosphate biosynthesis in gram-positive cocci J Bacteriol 182 4319 4327 CrossRef PubMed Wolf, YI, Kondrashov, AS, Koonin, EV 2000 Interkingdom gene fusions Genome Biol 1 1 13 CrossRef Yoshida, Y, Noshiro, M, Aoyama, Y, Kawamoto, T, Horiuchi, T, Gotoh, O 1997 Structural and evolutionary studies on sterol 14-demethylase P450 (CYP51), the most conserved P450 monooxygenase: II Evolutionary analysis of protein and gene structures. J Biochem (Tokyo) 122 1122 1128 Yoshida, Y, Aoyama, Y, Noshiro, M, Gotoh, O 2000 Sterol 14-demethylase P450 (CYP51) provides a breakthrough for the discussion on the evolution of cytochrome P450 gene superfamily Biochem Biophys Res Commun 273 799 804 CrossRef PubMed