Abstract
The nonproteinogenic amino acid 4-hydroxyphenylglycine (HPG) arises from the diversion of the tyrosine degradation pathway into secondary metabolism, and its biosynthesis requires a set of three enzymes. The gene cassette for HPG biosynthesis is widely spread in actinomycete bacteria, which incorporate the amino acid as a building block into various peptide antibiotics, but it has never been reported from another taxonomic group of eubacteria. A genome mining study has now revealed a putative HPG pathway in the predatory bacterium Herpetosiphon aurantiacus, which is phylogenetically distinct from Actinomycetes. Anomalies in the active center of one annotated key enzyme raised questions about the true product of this pathway, prompting an in vitro reconstitution attempt. This study confirmed the capability of H. aurantiacus for HPG production. Sequence analysis of the aberrant 4-hydroxymandelate synthase refines the existing model on the catalytic differentiation of iron(II)-dependent dioxygenases. Furthermore, we report a comprehensive analysis on the phylogeny of these enzymes, which sheds light on the evolution of paralogous gene sets and the ensuing metabolic diversity in a barely studied bacterium.
Abbreviations
- HPG:
-
4-Hydroxyphenylglycine
- HPPD:
-
4-Hydroxyphenylpyruvate dioxygenase
- HMS:
-
4-Hydroxymandelate synthase
- NRPS:
-
Nonribosomal peptide synthetase
- PKS:
-
Polyketide synthase
References
Abascal F, Zardoya R, Posada D (2005) ProtTest: selection of best-fit models of protein evolution. Bioinformatics 21:2104–2105
Andersson DI, Hughes D (2009) Gene amplification and adaptive evolution in bacteria. Annu Rev Genet 43:167–195
Böcker S, Hüffner F, Truss A, Wahlström M (2009) A faster fixed-parameter approach to drawing binary tanglegrams. LNCS 5917:38–49
Brownlee J, He P, Moran GR, Harrison DHT (2008) Two roads diverged: the structure of hydroxymandelate synthase from Amycolatopsis orientalis in complex with 4-hydroxymandelate. Biochemistry 47:2002–2013
Bryant DA, Frigaard NU (2006) Prokaryotic photosynthesis and phototrophy illuminated. Trends Microbiol 14:488–496
Cain CC, Lee D, Waldo RH, Henry AT, Casida EJ, Wani MC, Wall ME, Oberlies NH, Falkinham JO (2003) Synergistic antimicrobial activity of metabolites produced by a nonobligate bacterial predator. Antimicrobial Agents Chemother 47:2113–2117
Castenholz RW (2001) Order II. ‘Herpetosiphonales’. In: Boone DR, Castenholz RW (eds) Bergey’s manual of systematic bacteriology, vol 1, 2nd edn (The Archaea and the deeply branching and phototrophic Bacteria). Springer, New York, p 444
Choroba OW, Williams DH, Spencer JB (2000) Biosynthesis of the vancomycin group of antibiotics: involvement of an unusual dioxygenase in the pathway to (S)-4-hydroxyphenylglycine. J Am Chem Soc 122:5389–5390
Donadio S, Sosio M, Stegmann E, Weber T, Wohlleben W (2005) Comparative analysis and insights into the evolution of gene clusters for glycopeptide antibiotic biosynthesis. Mol Gen Genomics 274:40–50
Eustaquio AS, McGlinchey RP, Liu Y, Hazzard C, Beer LL, Florova G, Alhamadsheh MM, Lechner A, Kale AJ, Kobayashi Y, Reynolds KA, Moore BS (2009) Biosynthesis of the salinosporamide A polyketide synthase substrate chloroethylmalonyl-coenzyme A from S-adenosyl-l-methionine. Proc Natl Acad Sci USA 106:12295–12300
Felsenstein J (2005) Phylip: phylogenetic inference program Version 3.6. University of Washington, Seattle
Gevers D, Vandepoele K, Simillon C, Van de Peer Y (2004) Gene duplication and biased functional retention of paralogs in bacterial genomes. Trends Microbiol 12:148–154
Griebel T, Brinkmeyer M, Böcker S (2008) EPoS: a modular software framework for phylogenetic analysis. Bioinformatics 24:2399–2400
Gunsior M, Ravel J, Challis GL, Townsend CA (2004) Engineering p-hydroxyphenylpyruvate dioxygenase to a p-hydroxymandelate synthase and evidence for the proposed benzene oxide intermediate in homogentisate formation. Biochemistry 43:663–674
Hertweck C (2009) The biosynthetic logic of polyketide diversity. Angew Chem Int Ed 48:4688–4716
Hooper SD, Berg OG (2003) On the nature of gene innovation: duplication patterns in microbial genomes. Mol Biol Evol 20:945–954
Hubbard BK, Thomas MG, Walsh CT (2000) Biosynthesis of l-p-hydroxyphenylglycine, a non-proteinogenic amino acid constituent of peptide antibiotics. Chem Biol 7:931–942
Innan H, Kondrashov F (2010) The evolution of gene duplications: classifying and distinguishing between models. Nat Rev Genet 11:97–108
Jenke-Kodama H, Dittmann E (2009) Evolution of metabolic diversity: insights from microbial polyketide synthases. Phytochemistry 70:1858–1866
Jurkevitch E (2007) Predatory behaviors in bacteria—diversity and transitions. Microbe 2:67–73
Kawai S, Hanai K, Ito K, Kitahara S, Kuwae A (1991) High-performance liquid chromatographic separation of p-hydroxyphenylpyruvic acid. J Chromatogr 585:318–321
Klatt CG, Bryant DA, Ward DM (2007) Comparative genomics provides evidence for the 3-hydroxypropionate autotrophic pathway in filamentous anoxygenic phototrophic bacteria and in hot spring microbial mats. Environ Microbiol 9:2067–2078
Lawrence JG, Ochman H (1997) Amelioration of bacterial genomes: rates of change and exchange. J Mol Evol 44:383–397
Martin JF (1992) Clusters of genes for the biosynthesis of antibiotics: regulatory genes and overproduction of pharmaceuticals. J Ind Microbiol 9:73–90
Moran GR (2005) 4-Hydroxyphenylpyruvate dioxygenase. Arch Biochem Biophys 433:117–128
Neumann B, Pospiech A, Schairer HU (1992) Rapid isolation of genomic DNA from gram-negative bacteria. Trends Genet 8:332–333
O’Hare HM, Huang F, Holding A, Choroba OW, Spencer JB (2006) Conversion of hydroxyphenylpyruvate dioxygenases into hydroxymandelate synthases by directed evolution. FEBS Lett 580:3445–3450
Quinn GR, Skerman VBD (1980) Herpetosiphon—nature’s scavenger? Curr Microbiol 4:57–62
Röttig M, Medema MH, Blin K, Weber T, Rausch C, Kohlbacher O (2011) NRPSpredictor2—a web server for predicting NRPS adenylation domain specificity. Nucleic Acids Res 39(Suppl 2):W362–W367
Shah DD, Conrad JA, Heinz B, Brownlee JM, Moran GR (2011) Evidence for the mechanism of hydroxylation by 4-hydroxyphenylpyruvate dioxygenase and hydroxymandelate synthase from intermediate partitioning in active site variants. Biochemistry 50:7694–7704
Soskine M, Tawfik DS (2010) Mutational effects and the evolution of new protein functions. Nat Rev Genet 11:572–582
Stegmann E, Frasch H-J, Wohlleben W (2010) Glycopeptide biosynthesis in the context of basic cellular functions. Curr Opin Microbiol 13:595–602
Strieker M, Tanovic A, Marahiel MA (2010) Nonribosomal peptide synthetases: structures and dynamics. Curr Opin Struct Biol 20:234–240
Waterman MS, Smith TF, Singh M, Beyer WA (1977) Additive evolutionary trees. J Theor Biol 64:199–213
Widboom PF, Bruner SD (2009) Complex oxidation chemistry in the biosynthetic pathways to vancomycin/teicoplanin antibiotics. Chembiochem 10:1757–1764
Xiao Y, Wei X, Ebright R, Wall D (2011) Antibiotic production by myxobacteria plays a role in predation. J Bacteriol 193:4626–4633
Xu Z, Ding L, Hertweck C (2011) A branched extender unit shared between two orthogonal polyketide pathways in an endophyte. Angew Chem Int Ed 50:4667–4670
Acknowledgments
We thank A. Werner for help with the FPLC purification of MBP-Haur_1887.
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Communicated by Erko Stackebrandt.
Stephan Kastner and Sebastian Müller contributed equally to this work.
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Kastner, S., Müller, S., Natesan, L. et al. 4-Hydroxyphenylglycine biosynthesis in Herpetosiphon aurantiacus: a case of gene duplication and catalytic divergence. Arch Microbiol 194, 557–566 (2012). https://doi.org/10.1007/s00203-012-0789-y
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DOI: https://doi.org/10.1007/s00203-012-0789-y