Discovery and characterization of a prevalent human gut bacterial enzyme sufficient for the inactivation of a family of plant toxins

eLife

Volumn 7, Issue , 2018, Pages

  Koppel, Nitzan ^a   Bisanz, Jordan E ^b   Pandelia, Maria Eirini ^c   Turnbaugh, Peter J ^b,d   Balskus, Emily P ^a,e  

^a HARVARD UNIVERSITY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c BRANDEIS UNIVERSITY   (United States)

^d CHAN ZUCKERBERG BIOHUB   (United States)

^e BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; BACTERIAL ENZYME; CARDENOLIDE DERIVATIVE; CARDIAC GLYCOSIDE; DIGOXIN; OXIDOREDUCTASE; PLANT TOXIN; BACTERIAL PROTEIN; XENOBIOTIC AGENT;

ARTICLE; BACTERIAL STRAIN; EGGERTHELLA LENTA; GENE CLUSTER; GENE LOCUS; GENOMICS; INTESTINE FLORA; METAGENOMICS; NONHUMAN; OPERON; PROTEIN EXPRESSION; PROTEIN FUNCTION; BIOTRANSFORMATION; ENZYME SPECIFICITY; GASTROINTESTINAL TRACT; HUMAN; METABOLISM;

BACTERIAL PROTEINS; BIOTRANSFORMATION; DIGOXIN; GASTROINTESTINAL MICROBIOME; GASTROINTESTINAL TRACT; HUMANS; OXIDOREDUCTASES; SUBSTRATE SPECIFICITY; XENOBIOTICS;

EID: 85051989987     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.33953     Document Type: Article

References (99)

1. Agrawal AA, Petschenka G, Bingham RA, Weber MG, Rasmann S. 2012. Toxic cardenolides: chemical ecology and coevolution of specialized plant-herbivore interactions. New Phytologist 194:28–45. DOI: https://doi.org/10.1111/j.1469-8137.2011.04049.x, PMID: 22292897
2. Alam AN, Saha JR, Dobkin JF, Lindenbaum J. 1988. Interethnic variation in the metabolic inactivation of digoxin by the gut flora. Gastroenterology 95:117–123. DOI: https://doi.org/10.1016/0016-5085(88)90299-5, PMID: 3371607
3. Alva V, Nam SZ, Söding J, Lupas AN. 2016. The MPI bioinformatics Toolkit as an integrative platform for advanced protein sequence and structure analysis. Nucleic Acids Research 44:W410–W415. DOI: https://doi. org/10.1093/nar/gkw348, PMID: 27131380
4. Anders S, Pyl PT, Huber W. 2015. HTSeq–a Python framework to work with high-throughput sequencing data. Bioinformatics 31:166–169. DOI: https://doi.org/10.1093/bioinformatics/btu638
5. Atlschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ, Gapped B. 1997. and PSI-BLAST: a new generation of database search programs. Nucleic Acids Research 25:3389–3402. DOI: https://doi.org/10.1093/nar/25.17.3389
6. Ayala-Castro C, Saini A, Outten FW. 2008. Fe-S cluster assembly pathways in bacteria. Microbiology and Molecular Biology Reviews 72:110–125. DOI: https://doi.org/10.1128/MMBR.00034-07, PMID: 18322036
7. Backman TW, Cao Y, Girke T. 2011. ChemMine tools: an online service for analyzing and clustering small molecules. Nucleic Acids Research 39:W486–W491. DOI: https://doi.org/10.1093/nar/gkr320, PMID: 21576229
8. Banci L, Ciofi-Baffoni S, Mikolajczyk M, Winkelmann J, Bill E, Pandelia ME. 2013. Human anamorsin binds [2Fe-2S] clusters with unique electronic properties. Journal of Biological Inorganic Chemistry 18:883–893. DOI: https://doi.org/10.1007/s00775-013-1033-1, PMID: 23989406
9. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M, Kulikov AS, Lesin VM, Nikolenko SI, Pham S, Prjibelski AD, Pyshkin AV, Sirotkin AV, Vyahhi N, Tesler G, Alekseyev MA, Pevzner PA. 2012. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. Journal of Computational Biology 19:455– 477. DOI: https://doi.org/10.1089/cmb.2012.0021, PMID: 22506599
10. Bisanz JE, Soto Perez P, Lam KN, Bess EN, Haiser HJ, Allen-Vercoe E, Rekdal VM, Balskus EP, Turnbaugh PJ. 2018. Establishing a toolkit for genetics and ecology of the Coriobacteriia and Eggerthella lenta: prevalent symbionts of the gut microbiome. bioRxiv.
11. Bisanz JE, Turnbaugh PJ. 2018. ElenMatchR: Comparative Genomics Tool for Eggerthella Lenta and Coriobacteriia. Github. https://github.com/jbisanz/ElenMatchR
12. Bogachev AV, Bertsova YV, Bloch DA, Verkhovsky MI. 2012. Urocanate reductase: identification of a novel anaerobic respiratory pathway in Shewanella oneidensis MR-1. Molecular Microbiology 86:1452–1463. DOI: https://doi.org/10.1111/mmi.12067, PMID: 23078170
13. Bolger AM, Lohse M, Usadel B. 2014. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120. DOI: https://doi.org/10.1093/bioinformatics/btu170, PMID: 24695404
14. Bramkamp M, Lopez D. 2015. Exploring the existence of lipid rafts in bacteria. Microbiology and Molecular Biology Reviews 79:81–100. DOI: https://doi.org/10.1128/MMBR.00036-14, PMID: 25652542
15. Brzostek A, Sliwiński T, Rumijowska-Galewicz A, Korycka-Machała M, Dziadek J. 2005. Identification and targeted disruption of the gene encoding the main 3-ketosteroid dehydrogenase in Mycobacterium smegmatis. Microbiology 151:2393–2402. DOI: https://doi.org/10.1099/mic.0.27953-0, PMID: 16000729
16. Conover RC, Kowal AT, Fu WG, Park JB, Aono S, Adams MW, Johnson MK. 1990. Spectroscopic characterization of the novel iron-sulfur cluster in Pyrococcus furiosus ferredoxin. Journal of Biological Chemistry 265:8533– 8541. PMID: 2160461
17. Craciun S, Marks JA, Balskus EP. 2014. Characterization of choline trimethylamine-lyase expands the chemistry of glycyl radical enzymes. ACS Chemical Biology 9:1408–1413. DOI: https://doi.org/10.1021/cb500113p, PMID: 24854437
18. Dailey TA, Dailey HA. 2002. Identification of [2Fe-2S] clusters in microbial ferrochelatases. Journal of Bacteriology 184:2460–2464. DOI: https://doi.org/10.1128/JB.184.9.2460-2464.2002, PMID: 11948160
19. Devlin AS, Fischbach MA. 2015. A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nature Chemical Biology 11:685–690. DOI: https://doi.org/10.1038/nchembio.1864, PMID: 26192599
20. Dickert S, Pierik AJ, Buckel W. 2002. Molecular characterization of phenyllactate dehydratase and its initiator from Clostridium sporogenes. Molecular Microbiology 44:49–60. DOI: https://doi.org/10.1046/j.1365-2958. 2002.02867.x, PMID: 11967068
21. Dobbin PS, Butt JN, Powell AK, Reid GA, Richardson DJ. 1999. Characterization of a flavocytochrome that is induced during the anaerobic respiration of Fe3+ by Shewanella frigidimarina NCIMB400. Biochemical Journal 342:439–448. DOI: https://doi.org/10.1042/bj3420439, PMID: 10455032
22. Doherty MK, Pealing SL, Miles CS, Moysey R, Taylor P, Walkinshaw MD, Reid GA, Chapman SK. 2000. Identification of the active site acid/base catalyst in a bacterial fumarate reductase: a kinetic and crystallographic study. Biochemistry 39:10695–10701. DOI: https://doi.org/10.1021/bi000871l, PMID: 1097 8153
23. Dym O, Eisenberg D. 2001. Sequence-structure analysis of FAD-containing proteins. Protein Science 10:1712– 1728. DOI: https://doi.org/10.1110/ps.12801, PMID: 11514662
24. Gerlt JA, Bouvier JT, Davidson DB, Imker HJ, Sadkhin B, Slater DR, Whalen KL. 2015. Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST): A web tool for generating protein sequence similarity networks. Biochimica et Biophysica Acta 1854:1019–1037. DOI: https://doi.org/10.1016/j.bbapap.2015.04.015
25. Gheorghiade M, Adams KF, Colucci WS. 2004. Digoxin in the management of cardiovascular disorders. Circulation 109:2959–2964. DOI: https://doi.org/10.1161/01.CIR.0000132482.95686.87, PMID: 15210613
26. Goodman AL, Kallstrom G, Faith JJ, Reyes A, Moore A, Dantas G, Gordon JI. 2011. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. PNAS 108:6252–6257. DOI: https://doi.org/10.1073/pnas.1102938108, PMID: 21436049
27. Gorodetsky AA, Buzzeo MC, Barton JK. 2008. DNA-mediated electrochemistry. Bioconjugate Chemistry 19: 2285–2296. DOI: https://doi.org/10.1021/bc8003149, PMID: 18980370
28. Haiser HJ, Gootenberg DB, Chatman K, Sirasani G, Balskus EP, Turnbaugh PJ. 2013. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 341:295–298. DOI: https://doi.org/10.1126/science.1235872, PMID: 23869020
29. Haiser HJ, Seim KL, Balskus EP, Turnbaugh PJ. 2014. Mechanistic insight into digoxin inactivation by Eggerthella lenta augments our understanding of its pharmacokinetics. Gut Microbes 5:233–238. DOI: https://doi.org/10. 4161/gmic.27915, PMID: 24637603
30. Hao W, Golding GB. 2006. The fate of laterally transferred genes: life in the fast lane to adaptation or death. Genome Research 16:636–643. DOI: https://doi.org/10.1101/gr.4746406, PMID: 16651664
31. Hewitson KS, Ollagnier-de Choudens S, Sanakis Y, Shaw NM, Baldwin JE, Münck E, Roach PL, Fontecave M. 2002. The iron-sulfur center of biotin synthase: site-directed mutants. Journal of Biological Inorganic Chemistry 7:83–93. DOI: https://doi.org/10.1007/s007750100268, PMID: 11862544
32. Huh JR, Leung MW, Huang P, Ryan DA, Krout MR, Malapaka RR, Chow J, Manel N, Ciofani M, Kim SV, Cuesta A, Santori FR, Lafaille JJ, Xu HE, Gin DY, Rastinejad F, Littman DR. 2011. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity. Nature 472:486–490. DOI: https://doi.org/10.1038/nature09978, PMID: 21441909
33. Human Microbiome Project Consortium. 2012. Structure, function and diversity of the healthy human microbiome. Nature 486:207–214. DOI: https://doi.org/10.1038/nature11234, PMID: 22699609
34. Iismaa SE, Vázquez AE, Jensen GM, Stephens PJ, Butt JN, Armstrong FA, Burgess BK. 1991. Site-directed mutagenesis of Azotobacter vinelandii ferredoxin I. Changes in [4Fe-4S] cluster reduction potential and reactivity. Journal of Biological Chemistry 266:21563–21571. PMID: 1657971
35. Iverson TM, Luna-Chavez C, Croal LR, Cecchini G, Rees DC. 2002. Crystallographic studies of the Escherichia coli quinol-fumarate reductase with inhibitors bound to the quinol-binding site. Journal of Biological Chemistry 277:16124–16130. DOI: https://doi.org/10.1074/jbc.M200815200, PMID: 11850430
36. Iwasaki T, Okamoto K, Nishino T, Mizushima J, Hori H. 2000. Sequence motif-specific assignment of two [2Fe-2S] clusters in rat xanthine oxidoreductase studied by site-directed mutagenesis. Journal of Biochemistry 127:771– 778. DOI: https://doi.org/10.1093/oxfordjournals.jbchem.a022669, PMID: 10788785
37. Jung YS, Bonagura CA, Tilley GJ, Gao-Sheridan HS, Armstrong FA, Stout CD, Burgess BK. 2000. Structure of C42D Azotobacter vinelandii FdI. A Cys-X-X-Asp-X-X-Cys motif ligates an air-stable [4Fe-4S]2+/+ cluster. Journal of Biological Chemistry 275:36974–36983. DOI: https://doi.org/10.1074/jbc.M004947200, PMID: 10961 993
38. Kayali F, Janjua MA, Laber DA, Miller D, Kloecker G. 2011. Phase II trial of second-line erlotinib and digoxin for nonsmall cell lung cancer (NSCLC). Open Access Journal of Clinical Trials 3:9–13. DOI: https://doi.org/10.2147/OAJCT.S16347
39. Kemp GL, Clarke TA, Marritt SJ, Lockwood C, Poock SR, Hemmings AM, Richardson DJ, Cheesman MR, Butt JN. 2010. Kinetic and thermodynamic resolution of the interactions between sulfite and the pentahaem cytochrome NrfA from Escherichia coli. Biochemical Journal 431:73–80. DOI: https://doi.org/10.1042/BJ20100866, PMID: 20629638
40. Kern M, Einsle O, Simon J. 2008. Variants of the tetrahaem cytochrome c quinol dehydrogenase NrfH characterize the menaquinol-binding site, the haem c-binding motifs and the transmembrane segment. Biochemical Journal 414:73–79. DOI: https://doi.org/10.1042/BJ20080475, PMID: 18439144
41. Kern M, Simon J. 2011. Production of recombinant multiheme cytochromes c in Wolinella succinogenes. Methods in Enzymology 486:429–446. DOI: https://doi.org/10.1016/B978-0-12-381294-0.00019-5, PMID: 211 85447
42. Kleven MD, Dlakić M, Lawrence CM. 2015. Characterization of a single b-type heme, FAD, and metal binding sites in the transmembrane domain of six-transmembrane epithelial antigen of the prostate (STEAP) family proteins. Journal of Biological Chemistry 290:22558–22569. DOI: https://doi.org/10.1074/jbc.M115.664565, PMID: 26205815
43. Klinge S, Hirst J, Maman JD, Krude T, Pellegrini L. 2007. An iron-sulfur domain of the eukaryotic primase is essential for RNA primer synthesis. Nature Structural & Molecular Biology 14:875–877. DOI: https://doi.org/10. 1038/nsmb1288, PMID: 17704817
44. Delta(1) -dehydrogenase from Rhodococcus erythropolis SQSQ1 and its orthologue in Mycobacterium tuberculosis H37Rv are highly specific enzymes that function in cholesterol catabolism. Biochemical Journal 410:339–346. DOI: https://doi. org/10.1042/BJ20071130, PMID: 18031290
45. Koppel N, Maini Rekdal V, Balskus EP. 2017. Chemical transformation of xenobiotics by the human gut microbiota. Science 356:eaag2770. DOI: https://doi.org/10.1126/science.aag2770, PMID: 28642381
46. Kumano T, Fujiki E, Hashimoto Y, Kobayashi M. 2016. Discovery of a sesamin-metabolizing microorganism and a new enzyme. PNAS 113:9087–9092. DOI: https://doi.org/10.1073/pnas.1605050113, PMID: 27444012
47. Langmead B, Salzberg SL. 2012. Fast gapped-read alignment with Bowtie 2. Nature Methods 9:357–359. DOI: https://doi.org/10.1038/nmeth.1923, PMID: 22388286
48. + -ATPase compared with the ouabain-bound complex. PNAS 112:1755–1760. DOI: https://doi.org/10.1073/pnas.1422997112, PMID: 25624492
49. Lechner M, Findeiss S, Steiner L, Marz M, Stadler PF, Prohaska SJ. 2011. Proteinortho: detection of (co-) orthologs in large-scale analysis. BMC Bioinformatics 12:124. DOI: https://doi.org/10.1186/1471-2105-12-124, PMID: 21526987
50. Lee M, Gräwert T, Quitterer F, Rohdich F, Eppinger J, Eisenreich W, Bacher A, Groll M. 2010. Biosynthesis of isoprenoids: crystal structure of the [4Fe-4S] cluster protein IspG. Journal of Molecular Biology 404:600–610. DOI: https://doi.org/10.1016/j.jmb.2010.09.050, PMID: 20932974
51. Lee TT, Agarwalla S, Stroud RM. 2004. Crystal structure of RumA, an iron-sulfur cluster containing E. coli ribosomal RNA 5-methyluridine methyltransferase. Structure 12:397–407. DOI: https://doi.org/10.1016/j.str. 2004.02.009, PMID: 15016356
52. Leech HK, Raux E, McLean KJ, Munro AW, Robinson NJ, Borrelly GP, Malten M, Jahn D, Rigby SE, Heathcote P, Warren MJ. 2003. Characterization of the cobaltochelatase CbiXL: evidence for a 4Fe-4S center housed within an MXCXXC motif. Journal of Biological Chemistry 278:41900–41907. DOI: https://doi.org/10.1074/jbc. M306112200, PMID: 12917443
53. Leys D, Tsapin AS, Nealson KH, Meyer TE, Cusanovich MA, Van Beeumen JJ. 1999. Structure and mechanism of the flavocytochrome c fumarate reductase of Shewanella putrefaciens MR-1. Nature Structural Biology 6:1113– 1117. DOI: https://doi.org/10.1038/70051, PMID: 10581551
54. Lim B, Zimmermann M, Barry NA, Goodman AL. 2017. Engineered regulatory systems modulate gene expression of human commensals in the gut. Cell 169:547–558. DOI: https://doi.org/10.1016/j.cell.2017.03.045, PMID: 2 8431252
55. Lin J, Zhan T, Duffy D, Hoffman-Censits J, Kilpatrick D, Trabulsi EJ, Lallas CD, Chervoneva I, Limentani K, Kennedy B, Kessler S, Gomella L, Antonarakis ES, Carducci MA, Force T, Kelly WK. 2014. A pilot phase II study of digoxin in patients with recurrent prostate cancer as evident by a rising PSA. American Journal of Cancer Therapy and Pharmacology 2:21–32. PMID: 25580468
56. Lindenbaum J, Rund DG, Butler VP, Tse-Eng D, Saha JR. 1981b. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. New England Journal of Medicine 305:789–794. DOI: https://doi.org/10.1056/NEJM198110013051403, PMID: 7266632
57. Lindenbaum J, Tse-Eng D, Butler VP, Rund DG. 1981a. Urinary excretion of reduced metabolites of digoxin. American Journal of Medicine 71:67–74. DOI: https://doi.org/10.1016/0002-9343(81)90260-6, PMID: 7246583
58. Love MI, Huber W, Anders S. 2014. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology 15:550. DOI: https://doi.org/10.1186/s13059-014-0550-8, PMID: 25516281
59. Löffler FE, Sanford RA, Ritalahti KM. 2005. Enrichment, cultivation, and detection of reductively dechlorinating bacteria. Methods in Enzymology 397:77–111. DOI: https://doi.org/10.1016/S0076-6879(05)97005-5, PMID: 16260286
60. Marri PR, Hao W, Golding GB. 2006. Gene gain and gene loss in streptococcus: is it driven by habitat? Molecular Biology and Evolution 23:2379–2391. DOI: https://doi.org/10.1093/molbev/msl115, PMID: 16966682
61. Marri PR, Hao W, Golding GB. 2007. The role of laterally transferred genes in adaptive evolution. BMC Evolutionary Biology 7:S8. DOI: https://doi.org/10.1186/1471-2148-7-S1-S8, PMID: 17288581
62. Martín AE, Burgess BK, Stout CD, Cash VL, Dean DR, Jensen GM, Stephens PJ. 1990. Site-directed mutagenesis of Azotobacter vinelandii ferredoxin I: [Fe-S] cluster-driven protein rearrangement. PNAS 87:598–602. DOI: https://doi.org/10.1073/pnas.87.2.598, PMID: 2153958
63. Martínez-del Campo A, Bodea S, Hamer HA, Marks JA, Haiser HJ, Turnbaugh PJ, Balskus EP. 2015. Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria. mBio 6:e00042-15. DOI: https://doi.org/10.1128/mBio.00042-15, PMID: 25873372
64. Mathan VI, Wiederman J, Dobkin JF, Lindenbaum J. 1989. Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora. Gut 30:971–977. DOI: https://doi.org/10.1136/gut.30.7. 971, PMID: 2759492
65. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, et al. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65. DOI: https://doi.org/10.1038/nature08821, PMID: 20203603
66. Michalak M, Michalak K, Wicha J. 2017. The synthesis of cardenolide and bufadienolide aglycones, and related steroids bearing a heterocyclic subunit. Natural Product Reports 34:361–410. DOI: https://doi.org/10.1039/C6NP00107F, PMID: 28378871
67. Mitani Y, Meng X, Kamagata Y, Tamura T. 2005. Characterization of LtsA from Rhodococcus erythropolis, an enzyme with glutamine amidotransferase activity. Journal of Bacteriology 187:2582–2591. DOI: https://doi.org/10.1128/JB.187.8.2582-2591.2005, PMID: 15805504
68. Moore WEC, Cato EP, Holdeman LV. 1971. Eubacterium lentum (Eggerth) Prevot 1938: emendation of description and designation of the neotype strain. International Journal of Systematic Bacteriology 21:299–303. DOI: https://doi.org/10.1099/00207713-21-4-299
69. Morris CJ, Black AC, Pealing SL, Manson FD, Chapman SK, Reid GA, Gibson DM, Ward FB. 1994. Purification and properties of a novel cytochrome: flavocytochrome c from Shewanella putrefaciens. Biochemical Journal 302:587–593. DOI: https://doi.org/10.1042/bj3020587, PMID: 8093012
70. Nakamaru-Ogiso E, Yano T, Ohnishi T, Yagi T. 2002. Characterization of the iron-sulfur cluster coordinated by a cysteine cluster motif (CXXCXXXCX27C) in the Nqo3 subunit in the proton-translocating NADH-quinone oxidoreductase (NDH-1) of Thermus thermophilus HB-8. Journal of Biological Chemistry 277:1680–1688. DOI: https://doi.org/10.1074/jbc.M108796200, PMID: 11704668
71. Nakashima N, Tamura T. 2004a. Isolation and characterization of a rolling-circle-type plasmid from Rhodococcus erythropolis and application of the plasmid to multiple-recombinant-protein expression. Applied and Environmental Microbiology 70:5557–5568. DOI: https://doi.org/10.1128/AEM.70.9.5557-5568.2004, PMID: 15345444
72. ˚ C.T. 2004b. A novel system for expressing recombinant proteins over a wide temperature range from 4 to Biotechnology and Bioengineering 86:136–148. DOI: https://doi.org/10.1002/bit.20024, PMID: 15052633
73. Nayfach S, Fischbach MA, Pollard KS. 2015. MetaQuery: a web server for rapid annotation and quantitative analysis of specific genes in the human gut microbiome. Bioinformatics 31:3368–3370. DOI: https://doi.org/10. 1093/bioinformatics/btv382, PMID: 26104745
74. Nowell RW, Green S, Laue BE, Sharp PM. 2014. The extent of genome flux and its role in the differentiation of bacterial lineages. Genome Biology and Evolution 6:1514–1529. DOI: https://doi.org/10.1093/gbe/evu123, PMID: 24923323
75. Ozawa K, Yasukawa F, Fujiwara Y, Akutsu H. 2001. A simple, rapid, and highly efficient gene expression system for multiheme cytochromes c. Bioscience, Biotechnology, and Biochemistry 65:185–189. DOI: https://doi.org/10.1271/bbb.65.185, PMID: 11272827
76. Pandelia ME, Nitschke W, Infossi P, Giudici-Orticoni MT, Bill E, Lubitz W. 2011. Characterization of a unique [FeS] cluster in the electron transfer chain of the oxygen tolerant [NiFe] hydrogenase from Aquifex aeolicus. PNAS 108:6097–6102. DOI: https://doi.org/10.1073/pnas.1100610108, PMID: 21444783
77. Pealing SL, Black AC, Manson FD, Ward FB, Chapman SK, Reid GA. 1992. Sequence of the gene encoding flavocytochrome c from Shewanella putrefaciens: a tetraheme flavoenzyme that is a soluble fumarate reductase related to the membrane-bound enzymes from other bacteria. Biochemistry 31:12132–12140. DOI: https://doi. org/10.1021/bi00163a023, PMID: 1333793
78. Reid GA, Miles CS, Moysey RK, Pankhurst KL, Chapman SK. 2000. Catalysis in fumarate reductase. Biochimica et Biophysica Acta (BBA)-Bioenergetics 1459:310–315. DOI: https://doi.org/10.1016/S0005-2728(00)00166-3
79. Ridlon JM, Kang DJ, Hylemon PB. 2006. Bile salt biotransformations by human intestinal bacteria. Journal of Lipid Research 47:241–259. DOI: https://doi.org/10.1194/jlr.R500013-JLR200, PMID: 16299351
80. Rohman A, van Oosterwijk N, Thunnissen AM, Dijkstra BW. 2013. Crystal structure and site-directed mutagenesis of 3-ketosteroid ∆1-dehydrogenase from Rhodococcus erythropolis SQ1 explain its catalytic mechanism. Journal of Biological Chemistry 288:35559–35568. DOI: https://doi.org/10.1074/jbc.M113.522771, PMID: 24165124
81. Rothery EL, Mowat CG, Miles CS, Walkinshaw MD, Reid GA, Chapman SK. 2003. Histidine 61: an important heme ligand in the soluble fumarate reductase from Shewanella frigidimarina. Biochemistry 42:13160–13169. DOI: https://doi.org/10.1021/bi030159z, PMID: 14609326
82. Saha JR, Butler VP, Neu HC, Lindenbaum J. 1983. Digoxin-inactivating bacteria: Identification in human gut flora. Science 220:325–327. DOI: https://doi.org/10.1126/science.6836275, PMID: 6836275
83. Sanders C, Lill H. 2000. Expression of prokaryotic and eukaryotic cytochromesc in Escherichia coli. Biochimica Et Biophysica Acta (BBA)-Bioenergetics 1459:131–138. DOI: https://doi.org/10.1016/S0005-2728(00)00122-5
84. Saunders E, Pukall R, Abt B, Lapidus A, Glavina Del Rio T, Copeland A, Tice H, Cheng JF, Lucas S, Chen F, Nolan M, Bruce D, Goodwin L, Pitluck S, Ivanova N, Mavromatis K, Ovchinnikova G, Pati A, Chen A, Palaniappan K, et al. 2009. Complete genome sequence of Eggerthella lenta type strain (IPP VPI 0255). Standards in Genomic Sciences 1:174–182. DOI: https://doi.org/10.4056/sigs.33592, PMID: 21304654
85. Schiller C, Fröhlich CP, Giessmann T, Siegmund W, Mönnikes H, Hosten N, Weitschies W. 2005. Intestinal fluid volumes and transit of dosage forms as assessed by magnetic resonance imaging. Alimentary Pharmacology and Therapeutics 22:971–979. DOI: https://doi.org/10.1111/j.1365-2036.2005.02683.x, PMID: 16268972
86. Schnackerz KD, Dobritzsch D, Lindqvist Y, Cook PF. 2004. Dihydropyrimidine dehydrogenase: a flavoprotein with four iron–sulfur clusters. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 1701:61–74. DOI: https://doi.org/10.1016/j.bbapap.2004.06.009
87. Schneider D, Schmidt CL. 2005. Multiple Rieske proteins in prokaryotes: Where and why? Biochimica et Biophysica Acta (BBA)-Bioenergetics 1710:1–12. DOI: https://doi.org/10.1016/j.bbabio.2005.09.003
88. Seemann T. 2014. Prokka: rapid prokaryotic genome annotation. Bioinformatics 30:2068–2069. DOI: https://doi. org/10.1093/bioinformatics/btu153, PMID: 24642063
89. Segata N, Börnigen D, Morgan XC, Huttenhower C. 2013. PhyloPhlAn is a new method for improved phylogenetic and taxonomic placement of microbes. Nature Communications 4:2304. DOI: https://doi.org/10. 1038/ncomms3304, PMID: 23942190
90. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. 2003. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Research 13:2498–2504. DOI: https://doi.org/10.1101/gr.1239303, PMID: 14597658
91. Smith TW, Butler VP, Haber E. 1969. Determination of therapeutic and toxic serum digoxin concentrations by radioimmunoassay. New England Journal of Medicine 281:1212–1216. DOI: https://doi.org/10.1056/NEJM196911272812203, PMID: 5388455
92. Spanogiannopoulos P, Bess EN, Carmody RN, Turnbaugh PJ. 2016. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nature Reviews Microbiology 14:273–287. DOI: https://doi.org/10.1038/nrmicro.2016.17, PMID: 26972811
93. Thöny-Meyer L. 2002. Cytochrome c maturation: a complex pathway for a simple task? Biochemical Society Transactions 30:633–638. DOI: https://doi.org/10.1042/bst0300633, PMID: 12196152
94. Vos M, Hesselman MC, Te Beek TA, van Passel MWJ, Eyre-Walker A. 2015. Rates of lateral gene transfer in prokaryotes: high but why? Trends in Microbiology 23:598–605. DOI: https://doi.org/10.1016/j.tim.2015.07. 006, PMID: 26433693
95. Watanabe T, Honda K. 1982. Measurement of the extinction coefficient of the methyl viologen cation radical and the efficiency of its formation by semiconductor photocatalysis. Journal of Physical Chemistry 86:2617–2619. DOI: https://doi.org/10.1021/j100211a014
96. + -ATPase isoform selectivity for digitalis-like compounds is determined by two amino acids in the first extracellular loop. Chemical Research in Toxicology 27:2082–2092. DOI: https://doi.org/10.1021/tx500290k, PMID: 25361285
97. Weiner BE, Huang H, Dattilo BM, Nilges MJ, Fanning E, Chazin WJ. 2007. An iron-sulfur cluster in the C-terminal domain of the p58 subunit of human DNA primase. Journal of Biological Chemistry 282:33444–33451. DOI: https://doi.org/10.1074/jbc.M705826200, PMID: 17893144
98. Wong RW, Balachandran A, Ostrowski MA, Cochrane A. 2013. Digoxin suppresses HIV-1 replication by altering viral RNA processing. PLoS Pathogens 9:e1003241. DOI: https://doi.org/10.1371/journal.ppat.1003241, PMID: 23555254
99. Zhang Y, Zhu X, Torelli AT, Lee M, Dzikovski B, Koralewski RM, Wang E, Freed J, Krebs C, Ealick SE, Lin H. 2010. Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme. Nature 465:891– 896. DOI: https://doi.org/10.1038/nature09138, PMID: 20559380