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Cluster information : Pikromycin


close this sectionCompound

Entry namePikromycin
SynonymPicromycin
PKS TypeTypeI modular
Starter Unitmethylmalonyl-CoA
Chain Length7
Sugar Unitdesosamine
ClassificationMacrolide
ActivityAntibacterial
CompositionC28H47NO8
Pikromycin

close this sectionOriginal source

Organism
StrainATCC 15439
Contig

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close this sectionPKS/NRPS Module

Pikro_00030
pikAI
0 methylmalonyl-CoA
1 methylmalonyl-CoA
2 malonyl-CoA
Pikro_00040
pikAII
3 methylmalonyl-CoA
4 methylmalonyl-CoA
Pikro_00050
pikAIII
5 methylmalonyl-CoA
Pikro_00060
pikAIV
6 methylmalonyl-CoA
KSQ89..464
AT634..943
ACP1012..1082
KS1108..1485
AT1650..1960
KR2208..2387
ACP2497..2567
KS2604..2979
AT3180..3527
DH3579..3753
KR4100..4282
ACP4409..4479
KS36..412
AT572..881
kr1150..1345
ACP1443..1517
KS1539..1916
AT2069..2379
DH2428..2593
ER2959..3267
KR3277..3459
ACP3572..3642
KS35..413
AT565..873
KR1116..1295
ACP1405..1475
KS35..411
AT562..871
ACP944..1017
TE1127..1335

close this sectionReference

A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: architecture of metabolic diversity.
Xue Y, Zhao L, Liu HW, Sherman DH
[PMID: 9770448]Proc Natl Acad Sci U S A. 95 (1998) 12111-6
Characterization of the macrolide P-450 hydroxylase from Streptomyces venezuelae which converts narbomycin to picromycin.
Betlach MC, Kealey JT, Ashley GW, McDaniel R
[PMID: 9778370]Biochemistry. 37 (1998) 14937-42
Hydroxylation of macrolactones YC-17 and narbomycin is mediated by the pikC-encoded cytochrome P450 in Streptomyces venezuelae.
Xue Y, Wilson D, Zhao L, Liu H, Sherman DH
[PMID: 9831532]Chem Biol. 5 (1998) 661-7
Elucidating the mechanism of chain termination switching in the picromycin/methymycin polyketide synthase.
Tang L, Fu H, Betlach MC, McDaniel R
[PMID: 10421766]Chem Biol. 6 (1999) 553-8
Formation of functional heterologous complexes using subunits from the picromycin, erythromycin and oleandomycin polyketide synthases.
Tang L, Fu H, McDaniel R
[PMID: 10662693]Chem Biol. 7 (2000) 77-84
Alternative modular polyketide synthase expression controls macrolactone structure.
Xue Y, Sherman DH
[PMID: 10676969]Nature. 403 (2000) 571-5
Genetic architecture of the polyketide synthases for methymycin and pikromycin series macrolides.
Xue Y, Wilson D, Sherman DH
[PMID: 10713461]Gene. 245 (2000) 203-11
The Streptomyces venezuelae pikAV gene contains a transcription unit essential for expression of enzymes involved in glycosylation of narbonolide and 10-deoxymethynolide.
Chen S, Roberts JB, Xue Y, Sherman DH, Reynolds KA
[PMID: 11223265]Gene. 263 (2001) 255-64
Characterization and analysis of the PikD regulatory factor in the pikromycin biosynthetic pathway of Streptomyces venezuelae.
Wilson DJ, Xue Y, Reynolds KA, Sherman DH
[PMID: 11344155]J Bacteriol. 183 (2001) 3468-75
Isolation and structure determination of novamethymycin, a new bioactive metabolite of the methymycin biosynthetic pathway in Streptomyces venezuelae.
Zhang Q, Sherman DH
[PMID: 11720530]J Nat Prod. 64 (2001) 1447-50
The hidden steps of domain skipping: macrolactone ring size determination in the pikromycin modular polyketide synthase.
Beck BJ, Yoon YJ, Reynolds KA, Sherman DH
[PMID: 12031664]Chem Biol. 9 (2002) 575-83
Expression, purification, and characterization of two N,N-dimethyltransferases, tylM1 and desVI, involved in the biosynthesis of mycaminose and desosamine.
Chen H, Yamase H, Murakami K, Chang CW, Zhao L, Zhao Z, Liu HW
[PMID: 12119032]Biochemistry. 41 (2002) 9165-83
Biochemical evidence for an editing role of thioesterase II in the biosynthesis of the polyketide pikromycin.
Kim BS, Cropp TA, Beck BJ, Sherman DH, Reynolds KA
[PMID: 12368286]J Biol Chem. 277 (2002) 48028-34
Expression, site-directed mutagenesis, and steady state kinetic analysis of the terminal thioesterase domain of the methymycin/picromycin polyketide synthase.
Lu H, Tsai SC, Khosla C, Cane DE
[PMID: 12379101]Biochemistry. 41 (2002) 12590-7
Insights into channel architecture and substrate specificity from crystal structures of two macrocycle-forming thioesterases of modular polyketide synthases.
Tsai SC, Lu H, Cane DE, Khosla C, Stroud RM
[PMID: 12379102]Biochemistry. 41 (2002) 12598-606
Iterative chain elongation by a pikromycin monomodular polyketide synthase.
Beck BJ, Aldrich CC, Fecik RA, Reynolds KA, Sherman DH
[PMID: 12696866]J Am Chem Soc. 125 (2003) 4682-3
Expression and kinetic analysis of the substrate specificity of modules 5 and 6 of the picromycin/methymycin polyketide synthase.
Yin Y, Lu H, Khosla C, Cane DE
[PMID: 12733905]J Am Chem Soc. 125 (2003) 5671-6
Substrate recognition and channeling of monomodules from the pikromycin polyketide synthase.
Beck BJ, Aldrich CC, Fecik RA, Reynolds KA, Sherman DH
[PMID: 14531700]J Am Chem Soc. 125 (2003) 12551-7
High resolution X-ray structure of dTDP-glucose 4,6-dehydratase from Streptomyces venezuelae.
Allard ST, Cleland WW, Holden HM
[PMID: 14570895]J Biol Chem. 279 (2004) 2211-20
Beta-glucosylation as a part of self-resistance mechanism in methymycin/pikromycin producing strain Streptomyces venezuelae.
Zhao L, Beyer NJ, Borisova SA, Liu HW
[PMID: 14674753]Biochemistry. 42 (2003) 14794-804
Characterization of the glycosyltransferase activity of desVII: analysis of and implications for the biosynthesis of macrolide antibiotics.
Borisova SA, Zhao L, Melancon III CE, Kao CL, Liu HW
[PMID: 15161264]J Am Chem Soc. 126 (2004) 6534-5
New olivosyl derivatives of methymycin/pikromycin from an engineered strain of Streptomyces venezuelae.
Hong JS, Park SH, Choi CY, Sohng JK, Yoon YJ
[PMID: 15358425]FEMS Microbiol Lett. 238 (2004) 391-9
Biochemical investigation of pikromycin biosynthesis employing native penta- and hexaketide chain elongation intermediates.
Aldrich CC, Beck BJ, Fecik RA, Sherman DH
[PMID: 15941278]J Am Chem Soc. 127 (2005) 8441-52
Chemoenzymatic synthesis of the polyketide macrolactone 10-deoxymethynolide.
Aldrich CC, Venkatraman L, Sherman DH, Fecik RA
[PMID: 15969542]J Am Chem Soc. 127 (2005) 8910-1
Neopikromycin and novapikromycin from the pikromycin biosynthetic pathway of Streptomyces venezuelae.
Lee SK, Park JW, Kim JW, Jung WS, Park SR, Choi CY, Kim ES, Kim BS, Ahn JS, Sherman DH, Yoon YJ
[PMID: 16724858]J Nat Prod. 69 (2006) 847-9
The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae.
Sherman DH, Li S, Yermalitskaya LV, Kim Y, Smith JA, Waterman MR, Podust LM
[PMID: 16825192]J Biol Chem. 281 (2006) 26289-97
Structural basis for macrolactonization by the pikromycin thioesterase.
Akey DL, Kittendorf JD, Giraldes JW, Fecik RA, Sherman DH, Smith JL
[PMID: 16969372]Nat Chem Biol. 2 (2006) 537-42
Molecular architecture of DesV from Streptomyces venezuelae: a PLP-dependent transaminase involved in the biosynthesis of the unusual sugar desosamine.
Burgie ES, Thoden JB, Holden HM
[PMID: 17456741]Protein Sci. 16 (2007) 887-96
Molecular architecture of DesI: a key enzyme in the biosynthesis of desosamine.
Burgie ES, Holden HM
[PMID: 17630700]Biochemistry. 46 (2007) 8999-9006
Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase.
Kittendorf JD, Beck BJ, Buchholz TJ, Seufert W, Sherman DH
[PMID: 17719493]Chem Biol. 14 (2007) 944-54
Engineering and analysis of a self-sufficient biosynthetic cytochrome P450 PikC fused to the RhFRED reductase domain.
Li S, Podust LM, Sherman DH
[PMID: 17915876]J Am Chem Soc. 129 (2007) 12940-1
Enhanced heterologous production of desosaminyl macrolides and their hydroxylated derivatives by overexpression of the pikD regulatory gene in Streptomyces venezuelae.
Jung WS, Jeong SJ, Park SR, Choi CY, Park BC, Park JW, Yoon YJ
[PMID: 18245260]Appl Environ Microbiol. 74 (2008) 1972-9
The methymycin/pikromycin pathway: a model for metabolic diversity in natural product biosynthesis.
Kittendorf JD, Sherman DH
[PMID: 19027305]Bioorg Med Chem. 17 (2009) 2137-46
Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae.
Li S, Ouellet H, Sherman DH, Podust LM
[PMID: 19124459]J Biol Chem. 284 (2009) 5723-30
Characterization and mechanistic studies of DesII: a radical S-adenosyl-L-methionine enzyme involved in the biosynthesis of TDP-D-desosamine.
Szu PH, Ruszczycky MW, Choi SH, Yan F, Liu HW
[PMID: 19746907]J Am Chem Soc. 131 (2009) 14030-42
Synthesis and biochemical analysis of complex chain-elongation intermediates for interrogation of molecular specificity in the erythromycin and pikromycin polyketide synthases.
Mortison JD, Kittendorf JD, Sherman DH
[PMID: 19810731]J Am Chem Soc. 131 (2009) 15784-93
Selective oxidation of carbolide C-H bonds by an engineered macrolide P450 mono-oxygenase.
Li S, Chaulagain MR, Knauff AR, Podust LM, Montgomery J, Sherman DH
[PMID: 19833867]Proc Natl Acad Sci U S A. 106 (2009) 18463-8
Stoichiometry of the redox neutral deamination and oxidative dehydrogenation reactions catalyzed by the radical SAM enzyme DesII.
Ruszczycky MW, Choi SH, Liu HW
[PMID: 20121093]J Am Chem Soc. 132 (2010) 2359-69
Characterization of glycosyltransferase DesVII and its auxiliary partner protein DesVIII in the methymycin/picromycin biosynthetic pathway.
Borisova SA, Liu HW
[PMID: 20695498]Biochemistry. 49 (2010) 8071-84
Frontiers and opportunities in chemoenzymatic synthesis.
Mortison JD, Sherman DH
[PMID: 20882949]J Org Chem. 75 (2010) 7041-51
EPR-kinetic isotope effect study of the mechanism of radical-mediated dehydrogenation of an alcohol by the radical SAM enzyme DesII.
Ruszczycky MW, Choi SH, Liu HW
[PMID: 23329328]Proc Natl Acad Sci U S A. 110 (2013) 2088-93
Combinatorial biosynthesis and antibacterial evaluation of glycosylated derivatives of 12-membered macrolide antibiotic YC-17.
Shinde PB, Han AR, Cho J, Lee SR, Ban YH, Yoo YJ, Kim EJ, Kim E, Song MC, Park JW, Lee DG, Yoon YJ
[PMID: 23770075]J Biotechnol. (2013)
Biocatalytic synthesis of pikromycin, methymycin, neomethymycin, novamethymycin, and ketomethymycin.
Hansen DA, Rath CM, Eisman EB, Narayan AR, Kittendorf JD, Mortison JD, Yoon YJ, Sherman DH
[PMID: 23866020]J Am Chem Soc. 135 (2013) 11232-8
Directing group-controlled regioselectivity in an enzymatic C-H bond oxygenation.
Negretti S, Narayan AR, Chiou KC, Kells PM, Stachowski JL, Hansen DA, Podust LM, Montgomery J, Sherman DH
[PMID: 24627965]J Am Chem Soc. 136 (2014) 4901-4
Structure of a modular polyketide synthase.
Dutta S, Whicher JR, Hansen DA, Hale WA, Chemler JA, Congdon GR, Narayan AR, Hakansson K, Sherman DH, Smith JL, Skiniotis G
[PMID: 24965652]Nature. 510 (2014) 512-7
Structural rearrangements of a polyketide synthase module during its catalytic cycle.
Whicher JR, Dutta S, Hansen DA, Hale WA, Chemler JA, Dosey AM, Narayan AR, Hakansson K, Sherman DH, Smith JL, Skiniotis G
[PMID: 24965656]Nature. 510 (2014) 560-4
Elucidation of the cryptic epimerase activity of redox-inactive ketoreductase domains from modular polyketide synthases by tandem equilibrium isotope exchange.
Garg A, Xie X, Keatinge-Clay A, Khosla C, Cane DE
[PMID: 25004372]J Am Chem Soc. 136 (2014) 10190-3
Polyketide intermediate mimics as probes for revealing cryptic stereochemistry of ketoreductase domains.
Li Y, Fiers WD, Bernard SM, Smith JL, Aldrich CC, Fecik RA
[PMID: 25299319]ACS Chem Biol. 9 (2014) 2914-22
Modular polyketide synthases (PKSs): a new model fits all?
Rittner A, Grininger M
[PMID: 25318851]Chembiochem. 15 (2014) 2489-93
Substrate controlled divergence in polyketide synthase catalysis.
Hansen DA, Koch AA, Sherman DH
[PMID: 25730816]J Am Chem Soc. 137 (2015) 3735-8
Mechanistic Investigation of the Radical S-Adenosyl-L-methionine Enzyme DesII Using Fluorinated Analogues.
Lin GM, Choi SH, Ruszczycky MW, Liu HW
[PMID: 25826575]J Am Chem Soc. 137 (2015) 4964-7
Functional Characterization of a Dehydratase Domain from the Pikromycin Polyketide Synthase.
Li Y, Dodge GJ, Fiers WD, Fecik RA, Smith JL, Aldrich CC
[PMID: 26027428]J Am Chem Soc. 137 (2015) 7003-6
Enzymatic hydroxylation of an unactivated methylene C-H bond guided by molecular dynamics simulations.
Narayan AR, Jimenez-Oses G, Liu P, Negretti S, Zhao W, Gilbert MM, Ramabhadran RO, Yang YF, Furan LR, Li Z, Podust LM, Montgomery J, Houk KN, Sherman DH
[PMID: 26201742]Nat Chem. 7 (2015) 653-60
Resistance to ketolide antibiotics by coordinated expression of rRNA methyltransferases in a bacterial producer of natural ketolides.
Almutairi MM, Park SR, Rose S, Hansen DA, Vazquez-Laslop N, Douthwaite S, Sherman DH, Mankin AS
[PMID: 26438831]Proc Natl Acad Sci U S A. 112 (2015) 12956-61
In vivo investigation to the macrolide-glycosylating enzyme pair DesVII/DesVIII in Saccharopolyspora erythraea.
Wu H, Li W, Xin C, Zhang C, Wang Y, Ren S, Ren M, Zhao W, Yuan L, Xu Z, Yuan H, Geng M, Zhang L, Weaver DT, Zhang B
[PMID: 26552796]Appl Microbiol Biotechnol. 100 (2016) 2257-66
Interspecies Complementation of the LuxR Family Pathway-Specific Regulator Involved in Macrolide Biosynthesis.
Mo S, Yoon YJ
[PMID: 26608164]J Microbiol Biotechnol. 26 (2016) 66-71
Complete genome sequence of Streptomyces venezuelae ATCC 15439, a promising cell factory for production of secondary metabolites.
Song JY, Yoo YJ, Lim SK, Cha SH, Kim JE, Roe JH, Kim JF, Yoon YJ
[PMID: 26718561]J Biotechnol. 219 (2016) 57-8
Epimerase and Reductase Activities of Polyketide Synthase Ketoreductase Domains Utilize the Same Conserved Tyrosine and Serine Residues.
Xie X, Garg A, Keatinge-Clay AT, Khosla C, Cane DE
[PMID: 26863427]Biochemistry. 55 (2016) 1179-86
Complete Genome Sequence of Streptomyces venezuelae ATCC 15439, Producer of the Methymycin/Pikromycin Family of Macrolide Antibiotics, Using PacBio Technology.
He J, Sundararajan A, Devitt NP, Schilkey FD, Ramaraj T, Melancon CE 3rd
[PMID: 27151802]Genome Announc. 4 (2016)
Thioesterase domain swapping of a linear polyketide tautomycetin with a macrocyclic polyketide pikromycin in Streptomyces sp. CK4412.
Tripathi A, Choi SS, Sherman DH, Kim ES
[PMID: 27277081]J Ind Microbiol Biotechnol. 43 (2016) 1189-93

close this sectionData download

Compound nameGenomic
nucleotide
sequence
Nucleotide
sequences of the
coding regions
Translation of the
coding sequences
List of genes/ORFsGBK
Pikromycin
Genomic nucleotide sequence
55 KB
Nucleotide sequences of the coding regions
16 KB
Translation of the coding sequences
10 KB
List of genes/ORFs
1 KB

 

 
GenBank format
109 KB
AF079138
Genomic nucleotide sequence
38 KB
Nucleotide sequences of the coding regions
37 KB
Translation of the coding sequences
13 KB
List of genes/ORFs
1 KB

 

 

 
AF079762
Genomic nucleotide sequence
13 KB
Nucleotide sequences of the coding regions
12 KB
Translation of the coding sequences
4 KB
List of genes/ORFs
2 KB

 

 

 
AF079139
Genomic nucleotide sequence
4 KB
Nucleotide sequences of the coding regions
4 KB
Translation of the coding sequences
2 KB
List of genes/ORFs
442 B

 

 

 

close this sectionHistory

  • 2016-12-27[Update]
  • 2016-01-27[Update]
  • 2014-06-25[Update]
  • 2014-03-10[Update]
  • 2013-09-04[Update]
  • 2013-05-28[Update]
  • 2013-01-16[Update]
  • 2012-10-02[Update]
  • 2012-03-28[Release]