Rifamycin : Cluster information

Compound

Entry name	Rifamycin
PKS Type	TypeI modular
Starter Unit	3-amino-5-hydroxybenzoic acid (AHBA)
Chain Length	11
Sugar Unit	none
Classification	Ansamycin
Activity	Antibacterial
Composition	SV: C₃₇H₄₇NO₁₂

Original source

Organism	Amycolatopsis mediterranei
Strain	S699
Contig	AF040570

PKS/NRPS Module

Rifam_00210 rifA	0
	1	methylmalonyl-CoA
	2	malonyl-CoA
	3	methylmalonyl-CoA
Rifam_00220 rifB	4	methylmalonyl-CoA
	5	methylmalonyl-CoA
	6	methylmalonyl-CoA
Rifam_00230 rifC	7	methylmalonyl-CoA
Rifam_00240 rifD	8	methylmalonyl-CoA
Rifam_00250 rifE	9	malonyl-CoA
Rifam_00250 rifE	10	methylmalonyl-CoA

A	34..436

PCP	541..611

KS	632..1004

AT	1144..1453

dh	1489..1634

KR	1829..2005

ACP	2104..2174

KS	2195..2568

AT	2717..3025

ACP	3077..3151

KS	3171..3546

AT	3694..4008

kr	4307..4475

ACP	4580..4650

KS	35..411

AT	561..877

DH	923..1085

KR	1346..1519

ACP	1624..1694

KS	1717..2090

AT	2241..2548

dh	2592..2726

KR	2954..3126

ACP	3231..3301

KS	3322..3698

AT	3847..4160

dh	4207..4369

KR	4657..4833

ACP	4932..5002

KS	36..408

AT	555..868

dh	911..1070

KR	1334..1509

ACP	1617..1687

KS	34..410

AT	563..879

dh	911..1107

KR	1300..1475

ACP	1575..1645

KS	31..402

AT	554..872

DH	918..1081

KR	1338..1513

ACP	1610..1680

KS	1702..2076

AT	2228..2541

DH	2585..2748

Reference

3-Amino-5-hydroxybenzoic acid synthase, the terminal enzyme in the formation of the precursor of mC7N units in rifamycin and related antibiotics.: Kim CG, Yu TW, Fryhle CB, Handa S, Floss HG
[PMID: 9497318]J Biol Chem. 273 (1998) 6030-40
Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699.: August PR, Tang L, Yoon YJ, Ning S, Muller R, Yu TW, Taylor M, Hoffmann D, Kim CG, Zhang X, Hutchinson CR, Floss HG
[PMID: 9512878]Chem Biol. 5 (1998) 69-79
Direct evidence that the rifamycin polyketide synthase assembles polyketide chains processively.: Yu TW, Shen Y, Doi-Katayama Y, Tang L, Park C, Moore BS, Richard Hutchinson C, Floss HG
[PMID: 10430893]Proc Natl Acad Sci U S A. 96 (1999) 9051-6
Crystal structure of 3-amino-5-hydroxybenzoic acid (AHBA) synthase.: Eads JC, Beeby M, Scapin G, Yu TW, Floss HG
[PMID: 10433690]Biochemistry. 38 (1999) 9840-9
Thioesterases and the premature termination of polyketide chain elongation in rifamycin B biosynthesis by Amycolatopsis mediterranei S699.: Doi-Katayama Y, Yoon YJ, Choi CY, Yu TW, Floss HG, Hutchinson CR
[PMID: 10908112]J Antibiot (Tokyo). 53 (2000) 484-95
Mutational analysis and reconstituted expression of the biosynthetic genes involved in the formation of 3-amino-5-hydroxybenzoic acid, the starter unit of rifamycin biosynthesis in amycolatopsis Mediterranei S699.: Yu TW, Muller R, Muller M, Zhang X, Draeger G, Kim CG, Leistner E, Floss HG
[PMID: 11278540]J Biol Chem. 276 (2001) 12546-55
The loading module of rifamycin synthetase is an adenylation-thiolation didomain with substrate tolerance for substituted benzoates.: Admiraal SJ, Walsh CT, Khosla C
[PMID: 11352749]Biochemistry. 40 (2001) 6116-23
Biosynthesis of 1-deoxy-1-imino-D-erythrose 4-phosphate: a defining metabolite in the aminoshikimate pathway.: Guo J, Frost JW
[PMID: 11804477]J Am Chem Soc. 124 (2002) 528-9
Expression and purification of the rifamycin amide synthase, RifF, an enzyme homologous to the prokaryotic arylamine N-acetyltransferases.: Pompeo F, Mushtaq A, Sim E
[PMID: 11812235]Protein Expr Purif. 24 (2002) 138-51
The loading and initial elongation modules of rifamycin synthetase collaborate to produce mixed aryl ketide products.: Admiraal SJ, Khosla C, Walsh CT
[PMID: 11955082]Biochemistry. 41 (2002) 5313-24
Kanosamine biosynthesis: a likely source of the aminoshikimate pathway's nitrogen atom.: Guo J, Frost JW
[PMID: 12207504]J Am Chem Soc. 124 (2002) 10642-3
Characterization of the early stage aminoshikimate pathway in the formation of 3-amino-5-hydroxybenzoic acid: the RifN protein specifically converts kanosamine into kanosamine 6-phosphate.: Arakawa K, Muller R, Mahmud T, Yu TW, Floss HG
[PMID: 12207505]J Am Chem Soc. 124 (2002) 10644-5
Isolation and characterization of 27-O-demethylrifamycin SV methyltransferase provides new insights into the post-PKS modification steps during the biosynthesis of the antitubercular drug rifamycin B by Amycolatopsis mediterranei S699.: Xu J, Mahmud T, Floss HG
[PMID: 12623077]Arch Biochem Biophys. 411 (2003) 277-88
A homologue of the Mycobacterium tuberculosis PapA5 protein, rif-orf20, is an acetyltransferase involved in the biosynthesis of antitubercular drug rifamycin B by Amycolatopsis mediterranei S699.: Xiong Y, Wu X, Mahmud T
[PMID: 15791687]Chembiochem. 6 (2005) 834-7
Identification of tailoring genes involved in the modification of the polyketide backbone of rifamycin B by Amycolatopsis mediterranei S699.: Xu J, Wan E, Kim CJ, Floss HG, Mahmud T
[PMID: 16079331]Microbiology. 151 (2005) 2515-28
RifP; a membrane protein involved in rifamycin export in Amycolatopsis mediterranei.: Absalon AE, Fernandez FJ, Olivares PX, Barrios-Gonzalez J, Campos C, Mejia A
[PMID: 17351715]Biotechnol Lett. 29 (2007) 951-8
Structure and functional analysis of RifR, the type II thioesterase from the rifamycin biosynthetic pathway.: Claxton HB, Akey DL, Silver MK, Admiraal SJ, Smith JL
[PMID: 19103602]J Biol Chem. 284 (2009) 5021-9
The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review.: Floss HG, Yu TW, Arakawa K
[PMID: 21081954]J Antibiot (Tokyo). 64 (2011) 35-44
Stereochemistry of reductions catalyzed by methyl-epimerizing ketoreductase domains of polyketide synthases.: You YO, Khosla C, Cane DE
[PMID: 23659177]J Am Chem Soc. 135 (2013) 7406-9
Coupled methyl group epimerization and reduction by polyketide synthase ketoreductase domains. Ketoreductase-catalyzed equilibrium isotope exchange.: Garg A, Khosla C, Cane DE
[PMID: 24161343]J Am Chem Soc. 135 (2013) 16324-7
Structure and stereospecificity of the dehydratase domain from the terminal module of the rifamycin polyketide synthase.: Gay D, You YO, Keatinge-Clay A, Cane DE
[PMID: 24274103]Biochemistry. 52 (2013) 8916-28
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
Substrate structure-activity relationships guide rational engineering of modular polyketide synthase ketoreductases.: Bailey CB, Pasman ME, Keatinge-Clay AT
[PMID: 26568113]Chem Commun (Camb). 52 (2016) 792-5
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