Rapam_00180 : CDS information

close this sectionLocation

Organism
StrainNRRL 5491
Entry nameRapamycin
Contig
Start / Stop / Direction93,945 / 92,992 / - [in whole cluster]
93,945 / 92,992 / - [in contig]
Locationcomplement(92992..93945) [in whole cluster]
complement(92992..93945) [in contig]
TypeCDS
Length954 bp (317 aa)
Click on the icon to see Genetic map.

close this sectionAnnotation

Category3.2 modification methylation
ProductC-16 O-methyltransferase
Product (GenBank)methyltransferase
Gene
Gene (GenBank)rapM
EC number2.1.1.-
Keyword
Note
Note (GenBank)
Reference
ACC
PmId
[7644502] The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin. (Proc Natl Acad Sci U S A. , 1995)
[8635730] Organisation of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of genes flanking the polyketide synthase. (Gene. , 1996)
[11372782] Deletion of rapQONML from the rapamycin gene cluster of Streptomyces hygroscopicus gives production of the 16-O-desmethyl-27-desmethoxy analog. (J Antibiot (Tokyo). , 2001)
[16990929] Rapamycin biosynthesis: Elucidation of gene product function. (Org Biomol Chem. , 2006)
comment
[PMID: 7644502](1995)
rapamycin生合成gene clusterの報告。配列解析。
RapM: methyltransferase

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[PMID: 8635730](1996)
PKS flanking genesの配列解析。
three potential SAM-dependent O-methyltransferases (MTases), RapI, RapM and RapQ.
これらはmacrocycleの後期修飾に関与している可能性がある。

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[PMID: 11372782](2001)
rapQONMLのdeletion mutantはpipecolateを添加すると、rapamycinの代わりにanalog 16-O-desmethyl-27-desmethoxyrapamycinを産生した。これは、rapNによってコードされるP450 hydroxylaseがC-27に特異的で、rapQとrapM によってコードされるO-methyltransferasesがC-16 and C-27でのhydroxyl基をメチル化することを示す。

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[PMID: 16990929](2006)
rapKIJMNOQL deletion mutant S.hygroscopicus MG2-10をrapMで相補すると、C-16でのみO-methylationされたpre-rapamycin(PKSから放出された後の最初の中間体。未修飾aglycon.)が得られる。
また、rapMを発現したS.lividans TK24株にpre-rapamycinを与えると、同じ化合物が得られた。

rapKIJMNOQL deletion mutant S.hygroscopicus MG2-10をrapMNOで相補すると、C-27でhydroxylateされ、C-16でmethylateされたpre-rapamycinを蓄積。

よって、RapMはC-16に特異的なO-methylationを担う。

close this sectionSequence

selected fasta
>C-16 O-methyltransferase [methyltransferase]
MIQPDVVTAFTAVRDINLDEPGTPQAETKAATFKSASSSIYDLAASMSAKGQLWNWGVHD
SEFVAEIEARLPGFTEYGTDGFSEQLYYLALRDLPKGLESCDGRTVLEVGCGMGEGLNFL
SRLVPTARMTGLDLAPKAIASATATLSRGDTLRFVQGDAEELPFEDSSVDVLVNIESSHT
YPNLGRFLREAARALRRGGALSHIDVFTRQRLEAMRRITTEIPELKWVSDHDISDQVRAA
VRRRMPPDSHLRSTLNKQRMNRLARTLALHSQITVFGGTFADYQPPASVKMLSRLGLVPP
MDSLPMETYRHQIAVRV
selected fasta
>C-16 O-methyltransferase [methyltransferase]
ATGATCCAACCCGACGTCGTGACCGCCTTCACAGCGGTTCGCGACATCAATCTCGACGAA
CCCGGCACCCCGCAGGCGGAGACGAAGGCCGCCACCTTCAAGTCCGCCAGCTCCTCCATC
TACGACCTCGCCGCCAGCATGTCGGCAAAGGGCCAGCTGTGGAACTGGGGTGTGCACGAT
TCCGAGTTCGTCGCCGAGATCGAGGCCAGGCTGCCCGGATTCACCGAGTACGGCACCGAC
GGATTCAGCGAGCAGCTCTACTACCTGGCCCTGCGCGACCTTCCGAAGGGCTTGGAGAGC
TGCGACGGCCGGACGGTCCTGGAGGTCGGCTGCGGAATGGGGGAGGGGCTCAACTTCCTG
TCCCGCCTCGTCCCCACCGCCCGGATGACCGGGCTGGACCTGGCGCCGAAGGCGATCGCC
AGCGCCACCGCCACGCTGTCCCGCGGCGATACCCTGCGGTTCGTCCAGGGCGACGCCGAG
GAACTGCCCTTCGAGGACTCCTCGGTGGATGTGCTCGTCAACATCGAGAGCTCGCACACC
TACCCCAATCTGGGACGTTTCCTGCGGGAGGCCGCGCGCGCGCTGCGCCGGGGTGGCGCC
CTTTCGCACATCGACGTGTTCACGCGGCAGCGCCTTGAGGCGATGCGTCGGATCACAACG
GAAATACCCGAACTGAAGTGGGTCAGCGATCACGACATCTCCGATCAAGTCCGTGCCGCG
GTGCGCCGGCGGATGCCCCCGGACAGTCACCTCCGCAGCACCCTGAACAAACAACGGATG
AACCGGCTTGCGCGCACGCTCGCCCTGCACAGCCAGATCACGGTGTTCGGCGGCACGTTC
GCGGACTACCAGCCGCCCGCTTCGGTCAAAATGCTCAGCCGGCTCGGCCTCGTGCCGCCG
ATGGACAGCCTGCCGATGGAAACCTATCGGCACCAGATCGCCGTCCGCGTGTGA

close this sectionFeature

BLASTP
Database:UniProtKB:2011_09
show BLAST table
InterPro
Database:interpro:38.0
IPR013216 Methyltransferase type 11 (Domain)
 [107-201]  1.8e-20 PF08241
PF08241   Methyltransf_11
SignalP
 [1-9]  0.111 Signal
Bacteria, Gram-negative   
 [1-26]  0.122 Signal
Bacteria, Gram-positive   
TMHMM No significant hit
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