1887

Abstract

A streptogramin type B antibiotic, virginiamycin S (VS), is produced by , together with a streptogramin type A antibiotic, virginiamycin M (VM), as its synergistic counterpart. VS is a cyclic hexadepsipeptide containing a nonproteinogenic amino acid, -phenylglycine (-pheGly), in its core structure. We have identified, in the left-hand extremity of the virginiamycin supercluster, two genes that direct VS biosynthesis with -pheGly incorporation. Transcriptional analysis revealed that , encoding a nonribosomal peptide synthetase, and , encoding a protein with homology to a hydroxyphenylacetyl-CoA dioxygenase, are under the transcriptional regulation of virginiae butanolide (VB), a small diffusing signalling molecule that governs virginiamycin production. Gene deletion of resulted in complete loss of VS production without any changes in VM production, suggesting that is required for VS biosynthesis. The abolished VS production in the disruptant was fully recovered either by the external addition of pheGly or by gene complementation, which indicates that VisG is involved in VS biosynthesis as the provider of an -pheGly molecule. A feeding experiment with -pheGly analogues suggested that VisF, which is responsible for the last condensation step, has high substrate specificity toward -pheGly.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.050203-0
2011-11-01
2019-12-08
Loading full text...

Full text loading...

/deliver/fulltext/micro/157/11/3213.html?itemId=/content/journal/micro/10.1099/mic.0.050203-0&mimeType=html&fmt=ahah

References

  1. Barrière J. C. , Berthaud N. , Beyer D. , Dutka-Malen S. , Paris J. M. , Desnottes J. F. . ( 1998; ). Recent developments in streptogramin research. . Curr Pharm Des 4:, 155–180.[PubMed]
    [Google Scholar]
  2. Bierman M. , Logan R. , O’Brien K. , Seno E. T. , Rao R. N. , Schoner B. E. . ( 1992; ). Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. . Gene 116:, 43–49. [CrossRef] [PubMed]
    [Google Scholar]
  3. Blanc V. , Blanche F. , Crouzet J. , Jacques N. , Lacroix P. , Thibaut D. , Zagorec M. , Debussche L. , de Crécy-Lagard V. . ( 1994; ). Polypeptides involved in streptogramin biosynthesis, nucleotide sequences coding for said polypeptides and use thereof. . US Patent no. 5 891 695.
    [Google Scholar]
  4. Buttner M. J. , Chater K. F. , Bibb M. J. . ( 1990; ). Cloning, disruption, and transcriptional analysis of three RNA polymerase sigma factor genes of Streptomyces coelicolor A3(2). . J Bacteriol 172:, 3367–3378.[PubMed]
    [Google Scholar]
  5. de Crécy-Lagard V. , Saurin W. , Thibaut D. , Gil P. , Naudin L. , Crouzet J. , Blanc V. . ( 1997; ). Streptogramin B biosynthesis in Streptomyces pristinaespiralis and Streptomyces virginiae: molecular characterization of the last structural peptide synthetase gene. . Antimicrob Agents Chemother 41:, 1904–1909.[PubMed]
    [Google Scholar]
  6. Di Giambattista M. , Chinali G. , Cocito C. . ( 1989; ). The molecular basis of the inhibitory activities of type A and type B synergimycins and related antibiotics on ribosomes. . J Antimicrob Chemother 24:, 485–507. [CrossRef] [PubMed]
    [Google Scholar]
  7. Heathcote M. L. , Staunton J. , Leadlay P. F. . ( 2001; ). Role of type II thioesterases: evidence for removal of short acyl chains produced by aberrant decarboxylation of chain extender units. . Chem Biol 8:, 207–220. [CrossRef] [PubMed]
    [Google Scholar]
  8. Hubbard B. K. , Thomas M. G. , Walsh C. T. . ( 2000; ). Biosynthesis of l-p-hydroxyphenylglycine, a non-proteinogenic amino acid constituent of peptide antibiotics. . Chem Biol 7:, 931–942. [CrossRef] [PubMed]
    [Google Scholar]
  9. Katayama M. , Sakai Y. , Okamoto S. , Ihara F. , Nihira T. , Yamada Y. . ( 1996; ). Gene organization in the ada–rplL region of Streptomyces virginiae . . Gene 171:, 135–136. [CrossRef] [PubMed]
    [Google Scholar]
  10. Kieser T. , Bibb M. J. , Buttner M. J. , Chater K. F. , Hopwood D. A. . ( 2000; ). Practical Streptomyces Genetics. Norwich, UK:: John Innes Foundation;.
    [Google Scholar]
  11. Kinoshita H. , Ipposhi H. , Okamoto S. , Nakano H. , Nihira T. , Yamada Y. . ( 1997; ). Butyrolactone autoregulator receptor protein (BarA) as a transcriptional regulator in Streptomyces virginiae . . J Bacteriol 179:, 6986–6993.[PubMed]
    [Google Scholar]
  12. Lamb S. S. , Patel T. , Koteva K. P. , Wright G. D. . ( 2006; ). Biosynthesis of sulfated glycopeptide antibiotics by using the sulfotransferase StaL. . Chem Biol 13:, 171–181. [CrossRef] [PubMed]
    [Google Scholar]
  13. Lee Y. J. , Kitani S. , Nihira T. . ( 2010; ). Null mutation analysis of an afsA-family gene, barX, that is involved in biosynthesis of the γ-butyrolactone autoregulator in Streptomyces virginiae . . Microbiology 156:, 206–210. [CrossRef] [PubMed]
    [Google Scholar]
  14. Manzella J. P. . ( 2001; ). Quinupristin-dalfopristin: a new antibiotic for severe Gram-positive infections. . Am Fam Physician 64:, 1863–1866.[PubMed]
    [Google Scholar]
  15. Matsuno K. , Yamada Y. , Lee C. K. , Nihira T. . ( 2004; ). Identification by gene deletion analysis of barB as a negative regulator controlling an early process of virginiamycin biosynthesis in Streptomyces virginiae . . Arch Microbiol 181:, 52–59. [CrossRef] [PubMed]
    [Google Scholar]
  16. Namwat W. , Kamioka Y. , Kinoshita H. , Yamada Y. , Nihira T. . ( 2002; ). Characterization of virginiamycin S biosynthetic genes from Streptomyces virginiae . . Gene 286:, 283–290. [CrossRef] [PubMed]
    [Google Scholar]
  17. Nihira T. , Shimizu Y. , Kim H. S. , Yamada Y. . ( 1988; ). Structure-activity relationships of virginiae butanolide C, an inducer of virginiamycin production in Streptomyces virginiae . . J Antibiot (Tokyo) 41:, 1828–1837.[PubMed] [CrossRef]
    [Google Scholar]
  18. Paget M. S. , Chamberlin L. , Atrih A. , Foster S. J. , Buttner M. J. . ( 1999; ). Evidence that the extracytoplasmic function sigma factor σE is required for normal cell wall structure in Streptomyces coelicolor A3(2). . J Bacteriol 181:, 204–211.[PubMed]
    [Google Scholar]
  19. Pfeifer V. , Nicholson G. J. , Ries J. , Recktenwald J. , Schefer A. B. , Shawky R. M. , Schröder J. , Wohlleben W. , Pelzer S. . ( 2001; ). A polyketide synthase in glycopeptide biosynthesis: the biosynthesis of the non-proteinogenic amino acid (S)-3,5-dihydroxyphenylglycine. . J Biol Chem 276:, 38370–38377. [CrossRef] [PubMed]
    [Google Scholar]
  20. Pootoolal J. , Thomas M. G. , Marshall C. G. , Neu J. M. , Hubbard B. K. , Walsh C. T. , Wright G. D. . ( 2002; ). Assembling the glycopeptide antibiotic scaffold: the biosynthesis of A47934 from Streptomyces toyocaensis NRRL15009. . Proc Natl Acad Sci U S A 99:, 8962–8967.[PubMed] [CrossRef]
    [Google Scholar]
  21. Puk O. , Huber P. , Bischoff D. , Recktenwald J. , Jung G. , Süssmuth R. D. , van Pée K. H. , Wohlleben W. , Pelzer S. . ( 2002; ). Glycopeptide biosynthesis in Amycolatopsis mediterranei DSM5908: function of a halogenase and a haloperoxidase/perhydrolase. . Chem Biol 9:, 225–235. [CrossRef] [PubMed]
    [Google Scholar]
  22. Pulsawat N. , Kitani S. , Nihira T. . ( 2007; ). Characterization of biosynthetic gene cluster for the production of virginiamycin M, a streptogramin type A antibiotic, in Streptomyces virginiae . . Gene 393:, 31–42. [CrossRef] [PubMed]
    [Google Scholar]
  23. Pulsawat N. , Kitani S. , Fukushima E. , Nihira T. . ( 2009; ). Hierarchical control of virginiamycin production in Streptomyces virginiae by three pathway-specific regulators: VmsS, VmsT and VmsR. . Microbiology 155:, 1250–1259. [CrossRef] [PubMed]
    [Google Scholar]
  24. Recktenwald J. , Shawky R. , Puk O. , Pfennig F. , Keller U. , Wohlleben W. , Pelzer S. . ( 2002; ). Nonribosomal biosynthesis of vancomycin-type antibiotics: a heptapeptide backbone and eight peptide synthetase modules. . Microbiology 148:, 1105–1118.[PubMed]
    [Google Scholar]
  25. Sambrook J. , Russell D. W. . ( 2001; ). Molecular Cloning: a Laboratory Manual, , 3rd edn.. Cold Spring Harbor, NY:: Cold Spring Harbor Laboratory;.
    [Google Scholar]
  26. Skinner D. D. , Morgenstern M. R. , Fedechko R. W. , Denoya C. D. . ( 1995; ). Cloning and sequencing of a cluster of genes encoding branched-chain α-keto acid dehydrogenase from Streptomyces avermitilis and the production of a functional E1 [α β] component in Escherichia coli . . J Bacteriol 177:, 183–190.[PubMed]
    [Google Scholar]
  27. Stachelhaus T. , Mootz H. D. , Marahiel M. A. . ( 1999; ). The specificity-conferring code of adenylation domains in nonribosomal peptide synthetases. . Chem Biol 6:, 493–505. [CrossRef] [PubMed]
    [Google Scholar]
  28. Tseng C. C. , Vaillancourt F. H. , Bruner S. D. , Walsh C. T. . ( 2004; ). DpgC is a metal- and cofactor-free 3,5-dihydroxyphenylacetyl-CoA 1,2-dioxygenase in the vancomycin biosynthetic pathway. . Chem Biol 11:, 1195–1203. [CrossRef] [PubMed]
    [Google Scholar]
  29. Yamada Y. , Nihira T. , Sakuda S. . ( 1997; ). Butyrolactone autoregulators, inducers of virginiamycin in Streptomyces virginiae . . In Biotechnology of Antibiotics, pp. 63–79. Edited by Strohl W. R. . . New York:: Marcel Dekker;.
    [Google Scholar]
  30. Yanagimoto M. . ( 1983; ). Novel actions of inducer in staphylomycin production by Streptomyces virginiae . . J Ferment Technol 61:, 443–448.
    [Google Scholar]
  31. Yin X. , Zabriskie T. M. . ( 2006; ). The enduracidin biosynthetic gene cluster from Streptomyces fungicidicus . . Microbiology 152:, 2969–2983. [CrossRef] [PubMed]
    [Google Scholar]
  32. Zhang W. , Heemstra J. R. Jr , Walsh C. T. , Imker H. J. . ( 2010; ). Activation of the pacidamycin PacL adenylation domain by MbtH-like proteins. . Biochemistry 49:, 9946–9947. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.050203-0
Loading
/content/journal/micro/10.1099/mic.0.050203-0
Loading

Data & Media loading...

Supplements

Supplementary table 

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error