A flavin-dependent halogenase from metagenomic analysis prefers bromination over chlorination

Neubauer P, Widmann C, Wibberg D, Schröder L, Frese M, Kottke T, Kalinowski J, Niemann H, Sewald N (2018)
PLOS ONE 13(5): e0196797.

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Abstract / Bemerkung
Flavin-dependent halogenases catalyse halogenation of aromatic compounds. In most cases, this reaction proceeds with high regioselectivity and requires only the presence of FADH2, oxygen, and halide salts. Since marine habitats contain high concentrations of halides, organisms populating the oceans might be valuable sources of yet undiscovered halogenases. A new Hidden-Markov-Model (HMM) based on the PFAM tryptophan halogenase model was used for the analysis of marine metagenomes. Eleven metagenomes were screened leading to the identification of 254 complete or partial putative flavin-dependent halogenase genes. One predicted halogenase gene (brvH) was selected, codon optimised for E. coli, and overexpressed. Substrate screening revealed that this enzyme represents an active flavin-dependent halogenase able to convert indole to 3-bromoindole. Remarkably, bromination prevails also in a large excess of chloride. The BrvH crystal structure is very similar to that of tryptophan halogenases but reveals a substrate binding site that is open to the solvent instead of being covered by a loop.
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Neubauer P, Widmann C, Wibberg D, et al. A flavin-dependent halogenase from metagenomic analysis prefers bromination over chlorination. PLOS ONE. 2018;13(5): e0196797.
Neubauer, P., Widmann, C., Wibberg, D., Schröder, L., Frese, M., Kottke, T., Kalinowski, J., et al. (2018). A flavin-dependent halogenase from metagenomic analysis prefers bromination over chlorination. PLOS ONE, 13(5), e0196797. doi:10.1371/journal.pone.0196797
Neubauer, P., Widmann, C., Wibberg, D., Schröder, L., Frese, M., Kottke, T., Kalinowski, J., Niemann, H., and Sewald, N. (2018). A flavin-dependent halogenase from metagenomic analysis prefers bromination over chlorination. PLOS ONE 13:e0196797.
Neubauer, P., et al., 2018. A flavin-dependent halogenase from metagenomic analysis prefers bromination over chlorination. PLOS ONE, 13(5): e0196797.
P. Neubauer, et al., “A flavin-dependent halogenase from metagenomic analysis prefers bromination over chlorination”, PLOS ONE, vol. 13, 2018, : e0196797.
Neubauer, P., Widmann, C., Wibberg, D., Schröder, L., Frese, M., Kottke, T., Kalinowski, J., Niemann, H., Sewald, N.: A flavin-dependent halogenase from metagenomic analysis prefers bromination over chlorination. PLOS ONE. 13, : e0196797 (2018).
Neubauer, Pia, Widmann, Christiane, Wibberg, Daniel, Schröder, Lea, Frese, Marcel, Kottke, Tilman, Kalinowski, Jörn, Niemann, Hartmut, and Sewald, Norbert. “A flavin-dependent halogenase from metagenomic analysis prefers bromination over chlorination”. PLOS ONE 13.5 (2018): e0196797.
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Two-Component FAD-Dependent Monooxygenases: Current Knowledge and Biotechnological Opportunities.
Heine T, van Berkel WJH, Gassner G, van Pée KH, Tischler D., Biology (Basel) 7(3), 2018
PMID: 30072664

59 References

Daten bereitgestellt von Europe PubMed Central.

Structure-activity relationships in a series of substituted indolocarbazoles: topoisomerase I and protein kinase C inhibition and antitumoral and antimicrobial properties.
Pereira ER, Belin L, Sancelme M, Prudhomme M, Ollier M, Rapp M, Severe D, Riou JF, Fabbro D, Meyer T., J. Med. Chem. 39(22), 1996
PMID: 8893841
Enzymatic halogenation catalyzed via a catalytic triad and by oxidoreductases.
van Pee KH, Keller S, Wage T, Wynands I, Schnerr H, Zehner S., Biol. Chem. 381(1), 2000
PMID: 10722044
Glycopeptide biosynthesis in Amycolatopsis mediterranei DSM5908: function of a halogenase and a haloperoxidase/perhydrolase.
Puk O, Huber P, Bischoff D, Recktenwald J, Jung G, Sussmuth RD, van Pee KH, Wohlleben W, Pelzer S., Chem. Biol. 9(2), 2002
PMID: 11880037
Chloromycetin, a New Antibiotic From a Soil Actinomycete.
Ehrlich J, Bartz QR, Smith RM, Joslyn DA, Burkholder PR., Science 106(2757), 1947
PMID: 17737966
Chloramphenicol biosynthesis: the structure of CmlS, a flavin-dependent halogenase showing a covalent flavin-aspartate bond.
Podzelinska K, Latimer R, Bhattacharya A, Vining LC, Zechel DL, Jia Z., J. Mol. Biol. 397(1), 2010
PMID: 20080101
The Vancomycin Group of Antibiotics and the Fight against Resistant Bacteria.
Williams DH, Bardsley B., Angew. Chem. Int. Ed. Engl. 38(9), 1999
PMID: 29711719
Recent approaches for the synthesis of modified cryptophycins.
Weiss C, Sammet B, Sewald N., Nat Prod Rep 30(7), 2013
PMID: 23732943
Biosynthetic characterization and chemoenzymatic assembly of the cryptophycins. Potent anticancer agents from cyanobionts.
Magarvey NA, Beck ZQ, Golakoti T, Ding Y, Huber U, Hemscheidt TK, Abelson D, Moore RE, Sherman DH., ACS Chem. Biol. 1(12), 2006
PMID: 17240975
Regioselective Enzymatic Halogenation of Substituted Tryptophan Derivatives using the FAD‐Dependent Halogenase RebH
M, ChemCatChem 6(5), 2014
Modular Combination of Enzymatic Halogenation of Tryptophan with Suzuki-Miyaura Cross-Coupling Reactions
M, ChemCatChem 8(10), 2016
Enzymatic halogenation of tryptophan on a gram scale.
Frese M, Sewald N., Angew. Chem. Int. Ed. Engl. 54(1), 2014
PMID: 25394328
Structure and action of the myxobacterial chondrochloren halogenase CndH: a new variant of FAD-dependent halogenases.
Buedenbender S, Rachid S, Muller R, Schulz GE., J. Mol. Biol. 385(2), 2008
PMID: 19000696
The biosynthetic gene cluster for the antitumor rebeccamycin: characterization and generation of indolocarbazole derivatives.
Sanchez C, Butovich IA, Brana AF, Rohr J, Mendez C, Salas JA., Chem. Biol. 9(4), 2002
PMID: 11983340
Functions encoded by pyrrolnitrin biosynthetic genes from Pseudomonas fluorescens
S, J. Bacteriol 180(7), 1998
A flavin-dependent tryptophan 6-halogenase and its use in modification of pyrrolnitrin biosynthesis
C, Biocatal. Biotransformation 24(6), 2006
A regioselective tryptophan 5-halogenase is involved in pyrroindomycin biosynthesis in Streptomyces rugosporus LL-42D005.
Zehner S, Kotzsch A, Bister B, Sussmuth RD, Mendez C, Salas JA, van Pee KH., Chem. Biol. 12(4), 2005
PMID: 15850981
Microbial biosynthesis of halometabolites.
van Pee KH., Arch. Microbiol. 175(4), 2001
PMID: 11382220
Structural insights into regioselectivity in the enzymatic chlorination of tryptophan.
Zhu X, De Laurentis W, Leang K, Herrmann J, Ihlefeld K, van Pee KH, Naismith JH., J. Mol. Biol. 391(1), 2009
PMID: 19501593
Dichlorination of a pyrrolyl-S-carrier protein by FADH2-dependent halogenase PltA during pyoluteorin biosynthesis.
Dorrestein PC, Yeh E, Garneau-Tsodikova S, Kelleher NL, Walsh CT., Proc. Natl. Acad. Sci. U.S.A. 102(39), 2005
PMID: 16162666
RadH: A Versatile Halogenase for Integration into Synthetic Pathways.
Menon BRK, Brandenburger E, Sharif HH, Klemstein U, Shepherd SA, Greaney MF, Micklefield J., Angew. Chem. Int. Ed. Engl. 56(39), 2017
PMID: 28722773
Function and Structure of MalA/MalA', Iterative Halogenases for Late-Stage C-H Functionalization of Indole Alkaloids.
Fraley AE, Garcia-Borras M, Tripathi A, Khare D, Mercado-Marin EV, Tran H, Dan Q, Webb GP, Watts KR, Crews P, Sarpong R, Williams RM, Smith JL, Houk KN, Sherman DH., J. Am. Chem. Soc. 139(34), 2017
PMID: 28777910
Tryptophan 7-halogenase (PrnA) structure suggests a mechanism for regioselective chlorination.
Dong C, Flecks S, Unversucht S, Haupt C, van Pee KH, Naismith JH., Science 309(5744), 2005
PMID: 16195462
Chlorination by a long-lived intermediate in the mechanism of flavin-dependent halogenases.
Yeh E, Blasiak LC, Koglin A, Drennan CL, Walsh CT., Biochemistry 46(5), 2007
PMID: 17260957
New insights into the mechanism of enzymatic chlorination of tryptophan.
Flecks S, Patallo EP, Zhu X, Ernyei AJ, Seifert G, Schneider A, Dong C, Naismith JH, van Pee KH., Angew. Chem. Int. Ed. Engl. 47(49), 2008
PMID: 18979475
Sequence-structure analysis of FAD-containing proteins.
Dym O, Eisenberg D., Protein Sci. 10(9), 2001
PMID: 11514662
A High-Throughput Fluorescence Assay to Determine the Activity of Tryptophan Halogenases.
Schnepel C, Minges H, Frese M, Sewald N., Angew. Chem. Int. Ed. Engl. 55(45), 2016
PMID: 27618794
A Structure-Guided Switch in the Regioselectivity of a Tryptophan Halogenase.
Shepherd SA, Menon BR, Fisk H, Struck AW, Levy C, Leys D, Micklefield J., Chembiochem 17(9), 2016
PMID: 26840773
An Unusual Flavin-Dependent Halogenase from the Metagenome of the Marine Sponge Theonella swinhoei WA.
Smith DRM, Uria AR, Helfrich EJN, Milbredt D, van Pee KH, Piel J, Goss RJM., ACS Chem. Biol. 12(5), 2017
PMID: 28198609
Bioinformatic analysis reveals high diversity of bacterial genes for laccase-like enzymes.
Ausec L, Zakrzewski M, Goesmann A, Schluter A, Mandic-Mulec I., PLoS ONE 6(10), 2011
PMID: 22022440
Successful heterologous expression of a novel chitinase identified by sequence analyses of the metagenome from a chitin-enriched soil sample.
Stoveken J, Singh R, Kolkenbrock S, Zakrzewski M, Wibberg D, Eikmeyer FG, Puhler A, Schluter A, Moerschbacher BM., J. Biotechnol. 201(), 2014
PMID: 25240439
Marine biology
P, 2013
Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1).
Tasdemir D, Mallon R, Greenstein M, Feldberg LR, Kim SC, Collins K, Wojciechowicz D, Mangalindan GC, Concepcion GP, Harper MK, Ireland CM., J. Med. Chem. 45(2), 2002
PMID: 11784156
Basic local alignment search tool.
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ., J. Mol. Biol. 215(3), 1990
PMID: 2231712
Challenges in homology search: HMMER3 and convergent evolution of coiled-coil regions.
Mistry J, Finn RD, Eddy SR, Bateman A, Punta M., Nucleic Acids Res. 41(12), 2013
PMID: 23598997
Prodigal: prokaryotic gene recognition and translation initiation site identification
D, Bioinformatics 11(), 2010
MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets.
Kumar S, Stecher G, Tamura K., Mol. Biol. Evol. 33(7), 2016
PMID: 27004904
Integration, scaling, space-group assignment and post-refinement.
Kabsch W., Acta Crystallogr. D Biol. Crystallogr. 66(Pt 2), 2010
PMID: 20124693
How good are my data and what is the resolution?
Evans PR, Murshudov GN., Acta Crystallogr. D Biol. Crystallogr. 69(Pt 7), 2013
PMID: 23793146
Phaser crystallographic software.
McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ., J Appl Crystallogr 40(Pt 4), 2007
PMID: 19461840
Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard.
Terwilliger TC, Grosse-Kunstleve RW, Afonine PV, Moriarty NW, Zwart PH, Hung LW, Read RJ, Adams PD., Acta Crystallogr. D Biol. Crystallogr. 64(Pt 1), 2007
PMID: 18094468
Features and development of Coot.
Emsley P, Lohkamp B, Scott WG, Cowtan K., Acta Crystallogr. D Biol. Crystallogr. 66(Pt 4), 2010
PMID: 20383002
Refinement of macromolecular structures by the maximum-likelihood method.
Murshudov GN, Vagin AA, Dodson EJ., Acta Crystallogr. D Biol. Crystallogr. 53(Pt 3), 1997
PMID: 15299926
MolProbity: all-atom structure validation for macromolecular crystallography.
Chen VB, Arendall WB 3rd, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, Murray LW, Richardson JS, Richardson DC., Acta Crystallogr. D Biol. Crystallogr. 66(Pt 1), 2009
PMID: 20057044

AUTHOR UNKNOWN, 0
Specific Enzymatic Halogenation-From the Discovery of Halogenated Enzymes to Their Applications In Vitro and In Vivo.
Weichold V, Milbredt D, van Pee KH., Angew. Chem. Int. Ed. Engl. 55(22), 2016
PMID: 27059664
antiSMASH 3.0-a comprehensive resource for the genome mining of biosynthetic gene clusters.
Weber T, Blin K, Duddela S, Krug D, Kim HU, Bruccoleri R, Lee SY, Fischbach MA, Muller R, Wohlleben W, Breitling R, Takano E, Medema MH., Nucleic Acids Res. 43(W1), 2015
PMID: 25948579
Biosynthesis of polybrominated aromatic organic compounds by marine bacteria.
Agarwal V, El Gamal AA, Yamanaka K, Poth D, Kersten RD, Schorn M, Allen EE, Moore BS., Nat. Chem. Biol. 10(8), 2014
PMID: 24974229
The amino acids surrounding the flavin 7a-methyl group determine the UVA spectral features of a LOV protein.
Raffelberg S, Gutt A, Gartner W, Mandalari C, Abbruzzetti S, Viappiani C, Losi A., Biol. Chem. 394(11), 2013
PMID: 23828427
Two Flavoenzymes Catalyze the Post-Translational Generation of 5-Chlorotryptophan and 2-Aminovinyl-Cysteine during NAI-107 Biosynthesis.
Ortega MA, Cogan DP, Mukherjee S, Garg N, Li B, Thibodeaux GN, Maffioli SI, Donadio S, Sosio M, Escano J, Smith L, Nair SK, van der Donk WA., ACS Chem. Biol. 12(2), 2017
PMID: 28032983

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