Rapamycin : Cluster information --- DoBISCUIT

Entry name	Rapamycin
PKS Type	PKS-NRPS hybrid
Starter Unit	4,5-dihydroxycyclohex-1-ene carboxylic acid
Chain Length	15
Sugar Unit	none
Classification	Other Macrocyclic Lactone
Activity	Immunosuppressive Antitumor Neuroprotective Antiaging
Composition	C₅₁H₇₉NO₁₃

Organism	Streptomyces rapamycinicus
Strain	NRRL 5491
Contig	X86780

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
Rapam_00130 rapP	16

A	35..438

ER	684..990

kr	1000..1143

PCP	1217..1287

KS	1308..1677

AT	1817..2120

DH	2160..2322

ER	2616..2921

KR	2931..3107

ACP	3197..3271

KS	3293..3659

AT	3795..4034

dh	4111..4258

KR	4521..4697

ACP	4785..4859

KS	4881..5246

AT	5386..5688

dh	5728..5889

er	6178..6483

kr	6493..6668

ACP	6758..6832

KS	6854..7222

AT	7362..7665

DH	7705..7866

KR	8144..8320

ACP	8410..8484

KS	33..402

AT	542..780

dh	858..1002

KR	1267..1443

ACP	1535..1605

KS	1626..1995

AT	2135..2438

dh	2478..2639

kr	2919..3095

ACP	3170..3244

KS	3266..3633

AT	3778..4081

DH	4121..4282

ER	4577..4882

KR	4892..5068

ACP	5158..5232

KS	5254..5620

AT	5756..5994

DH	6072..6233

KR	6510..6686

ACP	6774..6848

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. 289 (2014) 21142-52
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