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PMID: 21826462 Published · ppublish English Journal Article Review

Function of MbtH homologs in nonribosomal peptide biosynthesis and applications in secondary metabolite discovery.

Journal of industrial microbiology & biotechnology ·Vol. 38 ·No. 11 ·2011-11-00 ·Pages 1747-60

Baltz RH

Abstract

Mycobacterium tuberculosis encodes mycobactin, a peptide siderophore that is biosynthesized by a nonribosomal peptide synthetase (NRPS) mechanism. Within the mycobactin biosynthetic gene cluster is a gene that encodes a 71-amino-acid protein MbtH. Many other NRPS gene clusters harbor mbtH homologs, and recent genetic, biochemical, and structural studies have begun to shed light on the function(s) of these proteins. In some cases, MbtH-like proteins are required for biosynthesis of their cognate peptides, and non-cognate MbtH-like proteins have been shown to be partially complementary. Biochemical studies revealed that certain MbtH-like proteins participate in tight binding to NRPS proteins containing adenylation (A) domains where they stimulate adenylation reactions. Expression of MbtH-like proteins is important for a number of applications, including optimal production of native and genetically engineered secondary metabolites produced by mechanisms that employ NRPS enzymes. They also may serve as beacons to identify gifted actinomycetes and possibly other bacteria that encode multiple functional NRPS pathways for discovery of novel secondary metabolites by genome mining.

MeSH Terms
Actinobacteria/genetics,metabolism Amino Acid Sequence Bacteria/genetics,metabolism Bacterial Proteins/chemistry,genetics,physiology Fungal Proteins/genetics Molecular Sequence Data Mycobacterium tuberculosis/enzymology,genetics,metabolism Peptide Biosynthesis, Nucleic Acid-Independent Peptide Synthases/chemistry,genetics Siderophores/biosynthesis
Chemicals
Bacterial Proteins Fungal Proteins Siderophores Peptide Synthases
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Baltz Richard H
CognoGen Biotechnology Consulting, 6438 North Olney Street, Indianapolis, IN 46220, USA. rbaltz923@aol.com
References (62)
62 references, click to expand
  1. The lyngbyatoxin biosynthetic assembly line: chain release by four-electron reduction of a dipeptidyl thioester to the corresponding alcohol.
    J Am Chem Soc. 2007 Dec 26;129(51):15762-3 PMID: 18044902
  2. The 1.8 A crystal structure of PA2412, an MbtH-like protein from the pyoverdine cluster of Pseudomonas aeruginosa.
    J Biol Chem. 2007 Jul 13;282(28):20425-34 PMID: 17502378
  3. Cloning and characterization of sanO, a gene involved in nikkomycin biosynthesis in Streptomyces ansochromogenes.
    Lett Appl Microbiol. 2003;37(6):452-7 PMID: 14633098
  4. Daptomycin biosynthesis in Streptomyces roseosporus: cloning and analysis of the gene cluster and revision of peptide stereochemistry.
    Microbiology (Reading). 2005 May;151(Pt 5):1507-1523 PMID: 15870461
  5. Genome sequence of the streptomycin-producing microorganism Streptomyces griseus IFO 13350.
    J Bacteriol. 2008 Jun;190(11):4050-60 PMID: 18375553
  6. Complete genome sequence of the rifamycin SV-producing Amycolatopsis mediterranei U32 revealed its genetic characteristics in phylogeny and metabolism.
    Cell Res. 2010 Oct;20(10):1096-108 PMID: 20567260
  7. Molecular characterization of co-transcribed genes from Streptomyces tendae Tü901 involved in the biosynthesis of the peptidyl moiety and assembly of the peptidyl nucleoside antibiotic nikkomycin.
    Mol Gen Genet. 2001 Jan;264(5):662-73 PMID: 11212921
  8. Enzymatic production of (-)-indolactam V by LtxB, a cytochrome P450 monooxygenase.
    J Nat Prod. 2010 Jan;73(1):71-4 PMID: 20000453
  9. A glutamic acid 3-methyltransferase encoded by an accessory gene locus important for daptomycin biosynthesis in Streptomyces roseosporus.
    Mol Microbiol. 2006 Sep;61(5):1294-307 PMID: 16879412
  10. Molecular characterization of two genes from Streptomyces tendae Tü901 required for the formation of the 4-formyl-4-imidazolin-2-one-containing nucleoside moiety of the peptidyl nucleoside antibiotic nikkomycin.
    Eur J Biochem. 2000 Mar;267(6):1698-706 PMID: 10712601
  11. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  12. Strategies for the discovery of new natural products by genome mining.
    Chembiochem. 2009 Mar 2;10(4):625-33 PMID: 19165837
  13. Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters.
    Appl Environ Microbiol. 2005 May;71(5):2452-9 PMID: 15870333
  14. Strain improvement in actinomycetes in the postgenomic era.
    J Ind Microbiol Biotechnol. 2011 Jun;38(6):657-66 PMID: 21253811
  15. N-acylation during glidobactin biosynthesis by the tridomain nonribosomal peptide synthetase module GlbF.
    Chem Biol. 2010 Oct 29;17(10):1077-83 PMID: 21035730
  16. The vbs genes that direct synthesis of the siderophore vicibactin in Rhizobium leguminosarum: their expression in other genera requires ECF sigma factor RpoI.
    Mol Microbiol. 2002 Jun;44(5):1153-66 PMID: 12028377
  17. Effects of deletions of mbtH-like genes on clorobiocin biosynthesis in Streptomyces coelicolor.
    Microbiology (Reading). 2007 May;153(Pt 5):1413-1423 PMID: 17464055
  18. MbtH-like protein-mediated cross-talk between non-ribosomal peptide antibiotic and siderophore biosynthetic pathways in Streptomyces coelicolor M145.
    Microbiology (Reading). 2007 May;153(Pt 5):1405-1412 PMID: 17464054
  19. Development of a genetic system for combinatorial biosynthesis of lipopeptides in Streptomyces fradiae and heterologous expression of the A54145 biosynthesis gene cluster.
    Appl Environ Microbiol. 2010 Oct;76(20):6877-87 PMID: 20802082
  20. Biosynthetic pathway for mannopeptimycins, lipoglycopeptide antibiotics active against drug-resistant gram-positive pathogens.
    Antimicrob Agents Chemother. 2006 Jun;50(6):2167-77 PMID: 16723579
  21. New natural product biosynthetic chemistry discovered by genome mining.
    Nat Prod Rep. 2009 Aug;26(8):977-86 PMID: 19636446
  22. Crystal structure of OxyB, a cytochrome P450 implicated in an oxidative phenol coupling reaction during vancomycin biosynthesis.
    J Biol Chem. 2002 Dec 6;277(49):47476-85 PMID: 12207020
  23. Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis.
    Nat Biotechnol. 2003 May;21(5):526-31 PMID: 12692562
  24. Genetic engineering in Streptomyces roseosporus to produce hybrid lipopeptide antibiotics.
    Chem Biol. 2006 Mar;13(3):269-76 PMID: 16638532
  25. The enduracidin biosynthetic gene cluster from Streptomyces fungicidicus.
    Microbiology (Reading). 2006 Oct;152(Pt 10):2969-2983 PMID: 17005978
  26. Identification of the biosynthetic gene cluster and an additional gene for resistance to the antituberculosis drug capreomycin.
    Appl Environ Microbiol. 2007 Jul;73(13):4162-70 PMID: 17496129
  27. Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338.
    Nat Biotechnol. 2007 Apr;25(4):447-53 PMID: 17369815
  28. Polyketide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics.
    Nat Prod Rep. 2007 Oct;24(5):1073-109 PMID: 17898898
  29. Formation of beta-hydroxy histidine in the biosynthesis of nikkomycin antibiotics.
    Chem Biol. 2002 Jan;9(1):103-12 PMID: 11841943
  30. Genomics and the ancient origins of the daptomycin biosynthetic gene cluster.
    J Antibiot (Tokyo). 2010 Aug;63(8):506-11 PMID: 20648020
  31. The sequence of a 1.8-mb bacterial linear plasmid reveals a rich evolutionary reservoir of secondary metabolic pathways.
    Genome Biol Evol. 2010 Jul 12;2:212-24 PMID: 20624727
  32. Mining microbial genomes for new natural products and biosynthetic pathways.
    Microbiology (Reading). 2008 Jun;154(Pt 6):1555-1569 PMID: 18524911
  33. Production of novel lipopeptide antibiotics related to A54145 by Streptomyces fradiae mutants blocked in biosynthesis of modified amino acids and assignment of lptJ, lptK and lptL gene functions.
    J Antibiot (Tokyo). 2011 Jan;64(1):79-87 PMID: 21102596
  34. Renaissance in antibacterial discovery from actinomycetes.
    Curr Opin Pharmacol. 2008 Oct;8(5):557-63 PMID: 18524678
  35. Microevolutionary genomics of bacteria.
    Theor Popul Biol. 2002 Jun;61(4):435-47 PMID: 12167363
  36. Enzymatic tailoring of ornithine in the biosynthesis of the Rhizobium cyclic trihydroxamate siderophore vicibactin.
    J Am Chem Soc. 2009 Oct 28;131(42):15317-29 PMID: 19778043
  37. Combinatorial biosynthesis of novel antibiotics related to daptomycin.
    Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17462-7 PMID: 17090667
  38. Genetically engineered lipopeptide antibiotics related to A54145 and daptomycin with improved properties.
    Antimicrob Agents Chemother. 2010 Apr;54(4):1404-13 PMID: 20086142
  39. Tandem action of glycosyltransferases in the maturation of vancomycin and teicoplanin aglycones: novel glycopeptides.
    Biochemistry. 2001 Apr 17;40(15):4745-55 PMID: 11294642
  40. The small MbtH-like protein encoded by an internal gene of the balhimycin biosynthetic gene cluster is not required for glycopeptide production.
    FEMS Microbiol Lett. 2006 Sep;262(1):85-92 PMID: 16907743
  41. The lipopeptide antibiotic A54145 biosynthetic gene cluster from Streptomyces fradiae.
    J Ind Microbiol Biotechnol. 2006 Feb;33(2):129-40 PMID: 16208464
  42. Complementation of daptomycin dptA and dptD deletion mutations in trans and production of hybrid lipopeptide antibiotics.
    Microbiology (Reading). 2006 Oct;152(Pt 10):2993-3001 PMID: 17005980
  43. Organization of the teicoplanin gene cluster in Actinoplanes teichomyceticus.
    Microbiology (Reading). 2004 Jan;150(Pt 1):95-102 PMID: 14702401
  44. Identification of the biosynthetic gene cluster for the pacidamycin group of peptidyl nucleoside antibiotics.
    Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16828-33 PMID: 20826445
  45. Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin.
    Chem Biol. 1998 Nov;5(11):631-45 PMID: 9831524
  46. Identification of the coumermycin A(1) biosynthetic gene cluster of Streptomyces rishiriensis DSM 40489.
    Antimicrob Agents Chemother. 2000 Nov;44(11):3040-8 PMID: 11036020
  47. Identification and functional characterization of phenylglycine biosynthetic genes involved in pristinamycin biosynthesis in Streptomyces pristinaespiralis.
    J Biotechnol. 2011 Aug 20;155(1):63-7 PMID: 21146568
  48. Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor.
    Chem Biol. 2002 Nov;9(11):1175-87 PMID: 12445768
  49. Genomic islands link secondary metabolism to functional adaptation in marine Actinobacteria.
    ISME J. 2009 Oct;3(10):1193-203 PMID: 19474814
  50. Molecular cloning and sequence analysis of the clorobiocin biosynthetic gene cluster: new insights into the biosynthesis of aminocoumarin antibiotics.
    Microbiology (Reading). 2002 Dec;148(Pt 12):3901-3911 PMID: 12480894
  51. MbtH-like proteins as integral components of bacterial nonribosomal peptide synthetases.
    Biochemistry. 2010 Oct 19;49(41):8815-7 PMID: 20845982
  52. Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase.
    J Am Chem Soc. 2004 Sep 22;126(37):11432-3 PMID: 15366877
  53. The gene cluster for the biosynthesis of the glycopeptide antibiotic A40926 by nonomuraea species.
    Chem Biol. 2003 Jun;10(6):541-9 PMID: 12837387
  54. Strain improvement of Streptomyces roseosporus for daptomycin production by rational screening of He-Ne laser and NTG induced mutants and kinetic modeling.
    Appl Biochem Biotechnol. 2011 Mar;163(6):729-43 PMID: 20886375
  55. Deciphering tuberactinomycin biosynthesis: isolation, sequencing, and annotation of the viomycin biosynthetic gene cluster.
    Antimicrob Agents Chemother. 2003 Sep;47(9):2823-30 PMID: 12936980
  56. Trends in prokaryotic evolution revealed by comparison of closely related bacterial and archaeal genomes.
    J Bacteriol. 2009 Jan;191(1):65-73 PMID: 18978059
  57. Coumarin formation in novobiocin biosynthesis: beta-hydroxylation of the aminoacyl enzyme tyrosyl-S-NovH by a cytochrome P450 NovI.
    Chem Biol. 2001 Apr;8(4):301-12 PMID: 11325587
  58. Solution structure of Rv2377c-founding member of the MbtH-like protein family.
    Tuberculosis (Edinb). 2010 Jul;90(4):245-51 PMID: 20434955
  59. Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters.
    J Ind Microbiol Biotechnol. 2010 Aug;37(8):759-72 PMID: 20467781
  60. Sequencing and analysis of the biosynthetic gene cluster of the lipopeptide antibiotic Friulimicin in Actinoplanes friuliensis.
    Antimicrob Agents Chemother. 2007 Mar;51(3):1028-37 PMID: 17220414
  61. Activation of the pacidamycin PacL adenylation domain by MbtH-like proteins.
    Biochemistry. 2010 Nov 23;49(46):9946-7 PMID: 20964365
  62. Production of hybrid glycopeptide antibiotics in vitro and in Streptomyces toyocaensis.
    Chem Biol. 1997 Mar;4(3):195-202 PMID: 9115410
Article Info
Journal
Journal of industrial microbiology & biotechnology
Abbr.
J Ind Microbiol Biotechnol
ISSN
1476-5535
Published
2011-11-00
Epub
2011-00-09
Pages
1747-60
Language
English
Region
Germany
NLM ID
9705544
Subset
IM
Analysis Services
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