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Cluster information : Rapamycin


close this sectionCompound

Entry nameRapamycin
PKS TypePKS-NRPS hybrid
Starter Unit4,5-dihydroxycyclohex-1-ene carboxylic acid
Chain Length15
Sugar Unitnone
ClassificationOther Macrocyclic Lactone
ActivityImmunosuppressive
Antitumor
Neuroprotective
Antiaging
CompositionC51H79NO13
Rapamycin

close this sectionOriginal source

Organism
StrainNRRL 5491
Contig
Click on the icon to see Genetic map.

close this sectionPKS/NRPS Module

Rapam_00120
rapA
0
1 methylmalonyl-CoA
2 malonyl-CoA
3 methylmalonyl-CoA
4 methylmalonyl-CoA
Rapam_00110
rapB
5 malonyl-CoA
6 methylmalonyl-CoA
7 methylmalonyl-CoA
8 malonyl-CoA
9 malonyl-CoA
10 methylmalonyl-CoA
Rapam_00140
rapC
11 malonyl-CoA
12 malonyl-CoA
13 methylmalonyl-CoA
14 malonyl-CoA
Rapam_00130
rapP
15 L-pipecolate
16
A35..438
ER684..990
kr1000..1143
PCP1217..1287
KS1308..1677
AT1817..2120
DH2160..2322
ER2616..2921
KR2931..3107
ACP3197..3271
KS3293..3659
AT3795..4034
dh4111..4258
KR4521..4697
ACP4785..4859
KS4881..5246
AT5386..5688
dh5728..5889
er6178..6483
kr6493..6668
ACP6758..6832
KS6854..7222
AT7362..7665
DH7705..7866
KR8144..8320
ACP8410..8484
KS33..402
AT542..780
dh858..1002
KR1267..1443
ACP1535..1605
KS1626..1995
AT2135..2438
dh2478..2639
kr2919..3095
ACP3170..3244
KS3266..3633
AT3778..4081
DH4121..4282
ER4577..4882
KR4892..5068
ACP5158..5232
KS5254..5620
AT5756..5994
DH6072..6233
KR6510..6686
ACP6774..6848
KS6870..7238
AT7382..7620
DH7705..7866
KR8145..8321
ACP8409..8483
KS8505..8874
AT9012..9314
DH9362..9523
KR9800..9977
ACP10071..10141
KS34..404
AT544..782
dh860..1007
KR1270..1446
ACP1534..1608
KS1630..1995
AT2131..2368
dh2447..2590
KR2855..3031
ACP3121..3195
KS3217..3585
AT3725..4028
DH4068..4229
ER4525..4830
KR4840..5016
ACP5113..5186
KS5220..5591
AT5760..6075
ACP6137..6207
C39..332
A521..922
PCP1007..1074
C1092..1389

close this sectionReference

The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin.
Schwecke T, Aparicio JF, Molnar I, Konig A, Khaw LE, Haydock SF, Oliynyk M, Caffrey P, Cortes J, Lester JB, et al.
[PMID: 7644502]Proc Natl Acad Sci U S A. 92 (1995) 7839-43
Organisation of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of genes flanking the polyketide synthase.
Molnar I, Aparicio JF, Haydock SF, Khaw LE, Schwecke T, Konig A, Staunton J, Leadlay PF
[PMID: 8635730]Gene. 169 (1996) 1-7
Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of the enzymatic domains in the modular polyketide synthase.
Aparicio JF, Molnar I, Schwecke T, Konig A, Haydock SF, Khaw LE, Staunton J, Leadlay PF
[PMID: 8635756]Gene. 169 (1996) 9-16
The pipecolate-incorporating enzyme for the biosynthesis of the immunosuppressant rapamycin--nucleotide sequence analysis, disruption and heterologous expression of rapP from Streptomyces hygroscopicus.
Konig A, Schwecke T, Molnar I, Bohm GA, Lowden PA, Staunton J, Leadlay PF
[PMID: 9266694]Eur J Biochem. 247 (1997) 526-34
Mutational biosynthesis of novel rapamycins by a strain of Streptomyces hygroscopicus NRRL 5491 disrupted in rapL, encoding a putative lysine cyclodeaminase.
Khaw LE, Bohm GA, Metcalfe S, Staunton J, Leadlay PF
[PMID: 9473033]J Bacteriol. 180 (1998) 809-14
Deletion of rapQONML from the rapamycin gene cluster of Streptomyces hygroscopicus gives production of the 16-O-desmethyl-27-desmethoxy analog.
Chung L, Liu L, Patel S, Carney JR, Reeves CD
[PMID: 11372782]J Antibiot (Tokyo). 54 (2001) 250-6
Isolation and characterization of pre-rapamycin, the first macrocyclic intermediate in the biosynthesis of the immunosuppressant rapamycin by S. hygroscopicus.
Gregory MA, Gaisser S, Lill RE, Hong H, Sheridan RM, Wilkinson B, Petkovic H, Weston AJ, Carletti I, Lee HL, Staunton J, Leadlay PF
[PMID: 15127450]Angew Chem Int Ed Engl. 43 (2004) 2551-3
Biosynthesis of pipecolic acid by RapL, a lysine cyclodeaminase encoded in the rapamycin gene cluster.
Gatto GJ Jr, Boyne MT 2nd, Kelleher NL, Walsh CT
[PMID: 16536560]J Am Chem Soc. 128 (2006) 3838-47
Rapamycin biosynthesis: Elucidation of gene product function.
Gregory MA, Hong H, Lill RE, Gaisser S, Petkovic H, Low L, Sheehan LS, Carletti I, Ready SJ, Ward MJ, Kaja AL, Weston AJ, Challis IR, Leadlay PF, Martin CJ, Wilkinson B, Sheridan RM
[PMID: 16990929]Org Biomol Chem. 4 (2006) 3565-8
Roles of rapH and rapG in positive regulation of rapamycin biosynthesis in Streptomyces hygroscopicus.
Kuscer E, Coates N, Challis I, Gregory M, Wilkinson B, Sheridan R, Petkovic H
[PMID: 17468238]J Bacteriol. 189 (2007) 4756-63
Biosynthesis of rapamycin and its regulation: past achievements and recent progress.
Park SR, Yoo YJ, Ban YH, Yoon YJ
[PMID: 20588302]J Antibiot (Tokyo). 63 (2010) 434-41
Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously undescribed family of enzymes acting on chorismate.
Andexer JN, Kendrew SG, Nur-e-Alam M, Lazos O, Foster TA, Zimmermann AS, Warneck TD, Suthar D, Coates NJ, Koehn FE, Skotnicki JS, Carter GT, Gregory MA, Martin CJ, Moss SJ, Leadlay PF, Wilkinson B
[PMID: 21383123]Proc Natl Acad Sci U S A. 108 (2011) 4776-81
Modification of Rifamycin Polyketide Backbone Leads to Improved Drug Activity Against Rifampicin-Resistant Mycobacterium tuberculosis*
Nigam A, Almabruk KH, Saxena A, Yang J, Mukherjee U, Kaur H, Kohli P, Kumari R, Singh P, Zakharov LN, Singh Y, Mahmud T, Lal R
[PMID: 24923585]J Biol Chem. (2014)
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
Protein-Protein Interactions, Not Substrate Recognition, Dominate the Turnover of Chimeric Assembly Line Polyketide Synthases.
Klaus M, Ostrowski MP, Austerjost J, Robbins T, Lowry B, Cane DE, Khosla C
[PMID: 27246853]J Biol Chem. 291 (2016) 16404-15

close this sectionData download

Compound nameGenomic
nucleotide
sequence
Nucleotide
sequences of the
coding regions
Translation of the
coding sequences
List of genes/ORFsGBK
Rapamycin
Genomic nucleotide sequence
108 KB
Nucleotide sequences of the coding regions
107 KB
Translation of the coding sequences
37 KB
List of genes/ORFs
4 KB

 

 
GenBank format
200 KB

close this sectionHistory

  • 2016-12-27[Update]
  • 2014-06-25[Update]
  • 2013-09-04[Update]
  • 2012-03-28[Release]