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Microbiome Is a Functional Modifier of P450 Drug Metabolism

  • Joseph L. Dempsey
  • Julia Yue CuiEmail author
Microbiome (A Patterson, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Microbiome

Abstract

Host cytochrome P450s (P450s) play important roles in the bioactivation and detoxification of numerous therapeutic drugs, environmental toxicants, dietary factors, as well as endogenous compounds. Gut microbiome is increasingly recognized as our “second genome” that contributes to the xenobiotic biotransformation of the host, and the first-pass metabolism of many orally exposed chemicals is a joint effort between host drug-metabolizing enzymes including P450s and gut microbiome. Gut microbiome contributes to the drug metabolism via two distinct mechanisms: direct mechanism refers to the metabolism of drugs by microbial enzymes, among which reduction and hydrolysis (or deconjugation) are among the most important reactions, whereas indirect mechanism refers to the influence of host receptors and signaling pathways by microbial metabolites. Many types of microbial metabolites, such as secondary bile acids (BAs), short-chain fatty acids (SCFAs), and tryptophan metabolites, are known regulators of human diseases through modulating host xenobiotic-sensing receptors. To study the roles of gut microbiome in regulating host drug metabolism including P450s, several models including germ-free mice, antibiotics, or probiotics treatments, have been widely used. The present review summarized the current information regarding the interactions between the gut microbiome and the host P450s in xenobiotic biotransformation organs such as liver, intestine, and kidney, highlighting the remote sensing mechanisms underlying gut microbiome-mediated regulation of host xenobiotic biotransformation. In addition, the roles of bacterial, fungal, and other microbiome kingdom P450s, which is an understudied area of research in pharmacology and toxicology, are discussed.

Keywords

Gut microbiome Cytochrome P450s Xenobiotic metabolism Drug metabolism Personalized medicine Gut-liver axis 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

  1. 1.
    Zhang RK, Chen K, Huang X, Wohlschlager L, Renata H, Arnold FH. Enzymatic assembly of carbon-carbon bonds via iron-catalysed sp(3) C-H functionalization. Nature. 2019;565:67–72.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Chiang JYL, Ferrell JM. Bile acids as metabolic regulators and nutrient sensors. Annu Rev Nutr. 2019.Google Scholar
  3. 3.
    Nelson DR. Cytochrome P450 diversity in the tree of life. Biochim Biophys Acta, Proteins Proteomics. 1866;2018:141–54.Google Scholar
  4. 4.
    Ding X, Kaminsky LS. Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annu Rev Pharmacol Toxicol. 2003;43:149–73.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Paine MF, Hart HL, Ludington SS, Haining RL, Rettie AE, Zeldin DC. The human intestinal cytochrome P450 “pie”. Drug Metab Dispos. 2006;34:880–6.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Renaud HJ, Cui JY, Khan M, Klaassen CD. Tissue distribution and gender-divergent expression of 78 cytochrome P450 mRNAs in mice. Toxicol Sci. 2011;124:261–77.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138:103–41.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Knights KM, Rowland A, Miners JO. Renal drug metabolism in humans: the potential for drug-endobiotic interactions involving cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT). Br J Clin Pharmacol. 2013;76:587–602.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Xie F, Ding X, Zhang QY. An update on the role of intestinal cytochrome P450 enzymes in drug disposition. Acta Pharm Sin B. 2016;6:374–83.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Miners JO, Yang X, Knights KM, Zhang L. The role of the kidney in drug elimination: transport, metabolism, and the impact of kidney disease on drug clearance. Clin Pharmacol Ther. 2017;102:436–49.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Zhang QY, Dunbar D, Ostrowska A, Zeisloft S, Yang J, Kaminsky LS. Characterization of human small intestinal cytochromes P-450. Drug Metab Dispos. 1999;27:804–9.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Hart SN, Zhong XB. P450 oxidoreductase: genetic polymorphisms and implications for drug metabolism and toxicity. Expert Opin Drug Metab Toxicol. 2008;4:439–52.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Tracy TS, Chaudhry AS, Prasad B, Thummel KE, Schuetz EG, Zhong XB, et al. Interindividual variability in cytochrome P450-mediated drug metabolism. Drug Metab Dispos. 2016;44:343–51.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Yu AM, Zhong XB. Advanced knowledge in drug metabolism and pharmacokinetics. Acta Pharm Sin B. 2016;6:361–2.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Zhang J, Zhang J, Wang R. Gut microbiota modulates drug pharmacokinetics. Drug Metab Rev. 2018;50:357–68.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Fu ZD, Cui JY. Remote sensing between liver and intestine: importance of microbial metabolites. Curr Pharmacol Rep. 2017;3:101–13.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Spanogiannopoulos P, Bess EN, Carmody RN, Turnbaugh PJ. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat Rev Microbiol. 2016;14:273–87.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Hayashi H, Takahashi R, Nishi T, Sakamoto M, Benno Y. Molecular analysis of jejunal, ileal, caecal and recto-sigmoidal human colonic microbiota using 16S rRNA gene libraries and terminal restriction fragment length polymorphism. J Med Microbiol. 2005;54:1093–101.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Wang M, Ahrne S, Jeppsson B, Molin G. Comparison of bacterial diversity along the human intestinal tract by direct cloning and sequencing of 16S rRNA genes. FEMS Microbiol Ecol. 2005;54:219–31.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Donaldson GP, Lee SM, Mazmanian SK. Gut biogeography of the bacterial microbiota. Nat Rev Microbiol. 2016;14:20–32.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Hillman ET, Lu H, Yao T, Nakatsu CH. Microbial ecology along the gastrointestinal tract. Microbes Environ. 2017;32:300–13.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Crespo-Piazuelo D, Estelle J, Revilla M, Criado-Mesas L, Ramayo-Caldas Y, Ovilo C, et al. Characterization of bacterial microbiota compositions along the intestinal tract in pigs and their interactions and functions. Sci Rep. 2018;8:12727.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Seekatz AM, Schnizlein MK, Koenigsknecht MJ, Baker JR, Hasler WL, Bleske BE, et al. Spatial and temporal analysis of the stomach and small-intestinal microbiota in fasted healthy humans. mSphere. 2019;4.Google Scholar
  24. 24.
    Lloyd-Price J, Mahurkar A, Rahnavard G, Crabtree J, Orvis J, Hall AB, et al. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature. 2017;550:61–6.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Uno T, Kono M. Studies on the metabolism of sulfisoxazole. V. On the deacetylation of N-acetylsulfisoxazole by intestinal bacteria. Yakugaku Zasshi. 1961;81:1434–6.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Sjaastad O. Free and conjugated histamine in faeces from healthy individuals. Scand J Gastroenterol. 1966;1:1–8.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Scheline RR. Decarboxylation and demethylation of some phenolic benzoic acid derivatives by rat caecal contents. J Pharm Pharmacol. 1966;18:664–9.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Scheline RR. The decarboxylation of some phenolic acids by the rat. Acta Pharmacol Toxicol (Copenh). 1966;24:275–85.CrossRefGoogle Scholar
  30. 30.
    Scheline RR. Metabolism of phenolic acids by the rat intestinal microflora. Acta Pharmacol Toxicol (Copenh). 1968;26:189–205.CrossRefGoogle Scholar
  31. 31.
    Scheline RR. The metabolism of drugs and other organic compounds by the intestinal microflora. Acta Pharmacol Toxicol (Copenh). 1968;26:332–42.CrossRefGoogle Scholar
  32. 32.
    Griffiths LA, Smith GE. Metabolism of apigenin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro. Biochem J. 1972;128:901–11.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Griffiths LA, Smith GE. Metabolism of myricetin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro. Biochem J. 1972;130:141–51.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Meyer T, Scheline RR. 3,4,5-trimethoxycinnamic acid and related compounds. I. Metabolism by the rat intestinal microflora. Xenobiotica. 1972;2:383–90.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Smith GE, Griffiths LA. Metabolism of N-acylated and O-alkylated drugs by the intestinal microflora during anaerobic incubation in vitro. Xenobiotica. 1974;4:477–87.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A. 2001;98:3369–74.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Xie HJ, Broberg U, Griskevicius L, Lundgren S, Carlens S, Meurling L, et al. Alteration of pharmacokinetics of cyclophosphamide and suppression of the cytochrome p450 genes by ciprofloxacin. Bone Marrow Transplant. 2003;31:197–203.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Toda T, Ohi K, Kudo T, Yoshida T, Ikarashi N, Ito K, et al. Ciprofloxacin suppresses Cyp3a in mouse liver by reducing lithocholic acid-producing intestinal flora. Drug Metab Pharmacokinet. 2009;24:201–8.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Toda T, Saito N, Ikarashi N, Ito K, Yamamoto M, Ishige A, et al. Intestinal flora induces the expression of Cyp3a in the mouse liver. Xenobiotica. 2009;39:323–34.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Bjorkholm B, Bok CM, Lundin A, Rafter J, Hibberd ML, Pettersson S. Intestinal microbiota regulate xenobiotic metabolism in the liver. PLoS One. 2009;4:e6958.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Selwyn FP, Cheng SL, Bammler TK, Prasad B, Vrana M, Klaassen C, et al. Developmental regulation of drug-processing genes in livers of germ-free mice. Toxicol Sci. 2015;147:84–103.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Selwyn FP, Cui JY, Klaassen CD. RNA-Seq quantification of hepatic drug processing genes in germ-free mice. Drug Metab Dispos. 2015;43:1572–80.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Kuno T, Hirayama-Kurogi M, Ito S, Ohtsuki S. Effect of intestinal flora on protein expression of drug-metabolizing enzymes and transporters in the liver and kidney of germ-free and antibiotics-treated mice. Mol Pharm. 2016;13:2691–701.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Fu ZD, Selwyn FP, Cui JY, Klaassen CD. RNA-Seq profiling of intestinal expression of xenobiotic processing genes in germ-free mice. Drug Metab Dispos. 2017;45:1225–38.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Claus SP, Ellero SL, Berger B, Krause L, Bruttin A, Molina J, et al. Colonization-induced host-gut microbial metabolic interaction. MBio. 2011;2:e00271–10.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Selwyn FP, Cheng SL, Klaassen CD, Cui JY. Regulation of hepatic drug-metabolizing enzymes in germ-free mice by conventionalization and probiotics. Drug Metab Dispos. 2016;44:262–74.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Salden HJ, Bas BM. Endotoxin binding to platelets in blood from patients with a sepsis syndrome. Clin Chem. 1994;40:1575–9.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Sauter C, Wolfensberger C. Interferon in human serum after injection of endotoxin. Lancet. 1980;2:852–3.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Boes M, Prodeus AP, Schmidt T, Carroll MC, Chen J. A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection. J Exp Med. 1998;188:2381–6.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Roopchand DE, Carmody RN, Kuhn P, Moskal K, Rojas-Silva P, Turnbaugh PJ, et al. Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome. Diabetes. 2015;64:2847–58.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Galanos C, Freudenberg MA, Reutter W. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci U S A. 1979;76:5939–43.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Sun HY, Yan YJ, Li YH, Lv L. Reversing effects of ginsenosides on LPS-induced hepatic CYP3A11/3A4 dysfunction through the pregnane X receptor. J Ethnopharmacol. 2019;229:246–55.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Renton KW, Nicholson TE. Hepatic and central nervous system cytochrome P450 are down-regulated during lipopolysaccharide-evoked localized inflammation in brain. J Pharmacol Exp Ther. 2000;294:524–30.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Morgan ET, Dempsey JL, Mimche SM, Lamb TJ, Kulkarni S, Cui JY, et al. Physiological regulation of drug metabolism and transport: pregnancy, microbiome, inflammation, infection, and fasting. Drug Metab Dispos. 2018;46:503–13.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet AP, et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and toll-like receptor 4. Immunity. 2014;41:296–310.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Dempsey JL, Wang D, Siginir G, Fei Q, Raftery D, Gu H, et al. Pharmacological activation of PXR and CAR downregulates distinct bile acid-metabolizing intestinal bacteria and alters bile acid homeostasis. Toxicol Sci. 2019;168:40–60.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Caparros-Martin JA, Lareu RR, Ramsay JP, Peplies J, Reen FJ, Headlam HA, et al. Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism. Microbiome. 2017;5:95.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Ramadoss P, Marcus C, Perdew GH. Role of the aryl hydrocarbon receptor in drug metabolism. Expert Opin Drug Metab Toxicol. 2005;1:9–21.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Hubbard TD, Murray IA, Perdew GH. Indole and tryptophan metabolism: endogenous and dietary routes to ah receptor activation. Drug Metab Dispos. 2015;43:1522–35.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Zhang L, Nichols RG, Correll J, Murray IA, Tanaka N, Smith PB, et al. Persistent organic pollutants modify gut microbiota-host metabolic homeostasis in mice through aryl hydrocarbon receptor activation. Environ Health Perspect. 2015;123:679–88.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Hubbard TD, Murray IA, Bisson WH, Lahoti TS, Gowda K, Amin SG, et al. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. Sci Rep. 2015;5:12689.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Hubbard TD, Liu Q, Murray IA, Dong F, Miller C 3rd, Smith PB, et al. Microbiota metabolism promotes synthesis of the human Ah receptor agonist 2,8-dihydroxyquinoline. J Proteome Res. 2019;18:1715–24.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Marinelli L, Martin-Gallausiaux C, Bourhis JM, Beguet-Crespel F, Blottiere HM, Lapaque N. Identification of the novel role of butyrate as AhR ligand in human intestinal epithelial cells. Sci Rep. 2019;9:643.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Zhang L, Nichols RG, Patterson AD. The aryl hydrocarbon receptor as a moderator of host-microbiota communication. Curr Opin Toxicol. 2017;2:30–5.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Li CY, Lee S, Cade S, Kuo LJ, Schultz IR, Bhatt DK, et al. Novel interactions between gut microbiome and host drug-processing genes modify the hepatic metabolism of the environmental chemicals polybrominated diphenyl ethers. Drug Metab Dispos. 2017;45:1197–214.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Li CY, Dempsey JL, Wang D, Lee S, Weigel KM, Fei Q, et al. PBDEs altered gut microbiome and bile acid homeostasis in male C57BL/6 mice. Drug Metab Dispos. 2018;46:1226–40.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Scharek-Tedin L, Kreuzer-Redmer S, Twardziok SO, Siepert B, Klopfleisch R, Tedin K, et al. Probiotic treatment decreases the number of CD14-expressing cells in porcine milk which correlates with several intestinal immune parameters in the piglets. Front Immunol. 2015;6:108.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Popovic N, Djokic J, Brdaric E, Dinic M, Terzic-Vidojevic A, Golic N, et al. The influence of heat-killed Enterococcus faecium BGPAS1-3 on the tight junction protein expression and immune function in differentiated Caco-2 cells infected with listeria monocytogenes ATCC 19111. Front Microbiol. 2019;10:412.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Kim B, Wang YC, Hespen CW, Espinosa J, Salje J, Rangan KJ, et al. Enterococcus faecium secreted antigen a generates muropeptides to enhance host immunity and limit bacterial pathogenesis. Elife. 2019;8.Google Scholar
  70. 70.
    McKenney PT, Yan J, Vaubourgeix J, Becattini S, Lampen N, Motzer A, et al. Intestinal bile acids induce a morphotype switch in vancomycin-resistant enterococcus that facilitates intestinal colonization. Cell Host Microbe. 2019;25:695–705 e5.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Nelson DR. Progress in tracing the evolutionary paths of cytochrome P450. Biochim Biophys Acta. 1814;2011:14–8.Google Scholar
  72. 72.
    Parvez M, Qhanya LB, Mthakathi NT, Kgosiemang IK, Bamal HD, Pagadala NS, et al. Molecular evolutionary dynamics of cytochrome P450 monooxygenases across kingdoms: special focus on mycobacterial P450s. Sci Rep. 2016;6:33099.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Senate LM, Tjatji MP, Pillay K, Chen W, Zondo NM, Syed PR, et al. Similarities, variations, and evolution of cytochrome P450s in Streptomyces versus Mycobacterium. Sci Rep. 2019;9:3962.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Carmichael AB, Wong LL. Protein engineering of Bacillus megaterium CYP102. The oxidation of polycyclic aromatic hydrocarbons. Eur J Biochem. 2001;268:3117–25.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Di Luccia B, D'Apuzzo E, Varriale F, Baccigalupi L, Ricca E, Pollice A. Bacillus megaterium SF185 induces stress pathways and affects the cell cycle distribution of human intestinal epithelial cells. Benefic Microbes. 2016;7:609–20.CrossRefGoogle Scholar
  76. 76.
    Kim BH, Fulco AJ. Induction by barbiturates of a cytochrome P-450-dependent fatty acid monooxygenase in Bacillus megaterium: relationship between barbiturate structure and inducer activity. Biochem Biophys Res Commun. 1983;116:843–50.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Rajnarayanan RV, Rowley CW, Hopkins NE, Alworth WL. Regulation of phenobarbital-mediated induction of CYP102 (cytochrome P450(BM-3)) in Bacillus megaterium by phytochemicals from soy and green tea. J Agric Food Chem. 2001;49:4930–6.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    English NT, Rankin LC. Antioxidant-mediated attenuation of the induction of cytochrome P450BM-3(CYP102) by ibuprofen in Bacillus megaterium ATCC 14581. Biochem Pharmacol. 1997;54:443–50.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Kitamura S, Sugihara K, Sanoh S, Fujimoto N, Ohta S. Metabolic activation of proestrogens in the environment by cytochrome P450 system. J Health Sci. 2008;54:343–55.CrossRefGoogle Scholar
  80. 80.
    Van de Wiele T, Vanhaecke L, Boeckaert C, Peru K, Headley J, Verstraete W, et al. Human colon microbiota transform polycyclic aromatic hydrocarbons to estrogenic metabolites. Environ Health Perspect. 2005;113:6–10.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Sowada J, Schmalenberger A, Ebner I, Luch A, Tralau T. Degradation of benzo[a]pyrene by bacterial isolates from human skin. FEMS Microbiol Ecol. 2014;88:129–39.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Olicon-Hernandez DR, Gonzalez-Lopez J, Aranda E. Overview on the biochemical potential of filamentous fungi to degrade pharmaceutical compounds. Front Microbiol. 2017;8:1792.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Sang H, Hulvey JP, Green R, Xu H, Im J, Chang T, et al. A xenobiotic detoxification pathway through transcriptional regulation in filamentous fungi. MBio. 2018;9.Google Scholar
  84. 84.
    McLean MA, Maves SA, Weiss KE, Krepich S, Sligar SG. Characterization of a cytochrome P450 from the acidothermophilic archaea Sulfolobus solfataricus. Biochem Biophys Res Commun. 1998;252:166–72.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Ndifor AM, Ward SA, Howells RE. Cytochrome P-450 activity in malarial parasites and its possible relationship to chloroquine resistance. Mol Biochem Parasitol. 1990;41:251–7.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Barrett J. Cytochrome P450 in parasitic protozoa and helminths. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998;121:181–3.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Lamb DC, Lei L, Warrilow AG, Lepesheva GI, Mullins JG, Waterman MR, et al. The first virally encoded cytochrome p450. J Virol. 2009;83:8266–9.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Girvan HM, Munro AW. Applications of microbial cytochrome P450 enzymes in biotechnology and synthetic biology. Curr Opin Chem Biol. 2016;31:136–45.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Bhattacharya SS, Yadav JS. Microbial P450 enzymes in bioremediation and drug discovery: emerging potentials and challenges. Curr Protein Pept Sci. 2018;19:75–86.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Xu LH, Du YL. Rational and semi-rational engineering of cytochrome P450s for biotechnological applications. Synth Syst Biotechnol. 2018;3:283–90.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature. 2006;440:940–3.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Bernhardt R, Urlacher VB. Cytochromes P450 as promising catalysts for biotechnological application: chances and limitations. Appl Microbiol Biotechnol. 2014;98:6185–203.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    McLean KJ, Hans M, Meijrink B, van Scheppingen WB, Vollebregt A, Tee KL, et al. Single-step fermentative production of the cholesterol-lowering drug pravastatin via reprogramming of Penicillium chrysogenum. Proc Natl Acad Sci U S A. 2015;112:2847–52.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Biggs BW, Lim CG, Sagliani K, Shankar S, Stephanopoulos G, De Mey M, et al. Overcoming heterologous protein interdependency to optimize P450-mediated Taxol precursor synthesis in Escherichia coli. Proc Natl Acad Sci U S A. 2016;113:3209–14.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Zuo R, Zhang Y, Jiang C, Hackett JC, Loria R, Bruner SD, et al. Engineered P450 biocatalysts show improved activity and regio-promiscuity in aromatic nitration. Sci Rep. 2017;7:842.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Doolotkeldieva T, Konurbaeva M, Bobusheva S. Microbial communities in pesticide-contaminated soils in Kyrgyzstan and bioremediation possibilities. Environ Sci Pollut Res Int. 2018;25:31848–62.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Han J, Kim DH, Seo JS, Kim IC, Nelson DR, Puthumana J, et al. Assessing the identity and expression level of the cytochrome P450 20A1 (CYP20A1) gene in the BPA-, BDE-47, and WAF-exposed copepods Tigriopus japonicus and Paracyclopina nana. Comp Biochem Physiol C Toxicol Pharmacol. 2017;193:42–9.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Mtibaa R, Olicon-Hernandez DR, Pozo C, Nasri M, Mechichi T, Gonzalez J, et al. Degradation of bisphenol A and acute toxicity reduction by different thermo-tolerant ascomycete strains isolated from arid soils. Ecotoxicol Environ Saf. 2018;156:87–96.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Liang JL, JiangYang JH, Nie Y, Wu XL. Regulation of the alkane hydroxylase CYP153 gene in a gram-positive alkane-degrading bacterium, Dietzia sp. strain DQ12-45-1b. Appl Environ Microbiol. 2016;82:608–19.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    McCarl V, Somerville MV, Ly MA, Henry R, Liew EF, Wilson NL, et al. Heterologous expression of mycobacterium alkene monooxygenases in gram-positive and gram-negative bacterial hosts. Appl Environ Microbiol. 2018;84.Google Scholar
  101. 101.
    Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 2010;330:831–5.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Coelho PS, Brustad EM, Kannan A, Arnold FH. Olefin cyclopropanation via carbene transfer catalyzed by engineered cytochrome P450 enzymes. Science. 2013;339:307–10.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Coelho PS, Wang ZJ, Ener ME, Baril SA, Kannan A, Arnold FH, et al. A serine-substituted P450 catalyzes highly efficient carbene transfer to olefins in vivo. Nat Chem Biol. 2013;9:485–7.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Biernat KA, Pellock SJ, Bhatt AP, Bivins MM, Walton WG, Tran BNT, et al. Structure, function, and inhibition of drug reactivating human gut microbial beta-glucuronidases. Sci Rep. 2019;9:825.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Clayton TA, Baker D, Lindon JC, Everett JR, Nicholson JK. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc Natl Acad Sci U S A. 2009;106:14728–33.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Kim JK, Choi MS, Jeong JJ, Lim SM, Kim IS, Yoo HH, et al. Effect of probiotics on pharmacokinetics of orally administered acetaminophen in mice. Drug Metab Dispos. 2018;46:122–30.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Sweeny DJ, Li W, Clough J, Bhamidipati S, Singh R, Park G, et al. Metabolism of fostamatinib, the oral methylene phosphate prodrug of the spleen tyrosine kinase inhibitor R406 in humans: contribution of hepatic and gut bacterial processes to the overall biotransformation. Drug Metab Dispos. 2010;38:1166–76.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Boer J, Young-Sciame R, Lee F, Bowman KJ, Yang X, Shi JG, et al. Roles of UGT, P450, and gut microbiota in the metabolism of Epacadostat in humans. Drug Metab Dispos. 2016;44:1668–74.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Sousa T, Paterson R, Moore V, Carlsson A, Abrahamsson B, Basit AW. The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm. 2008;363:1–25.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Li H, Jia W. Cometabolism of microbes and host: implications for drug metabolism and drug-induced toxicity. Clin Pharmacol Ther. 2013;94:574–81.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Taneva E, Sinclair S, Mesquita PM, Weinrick B, Cameron SA, Cheshenko N, et al. Vaginal microbiome modulates topical antiretroviral drug pharmacokinetics. JCI Insight. 2018;3.Google Scholar
  112. 112.
    Wilson ID, Nicholson JK. Gut microbiome interactions with drug metabolism, efficacy, and toxicity. Transl Res. 2017;179:204–22.PubMedCrossRefPubMedCentralGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Environmental and Occupational Health SciencesUniversity of WashingtonSeattleUSA

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