Rapam_00200 Rapam_00200   Rapam_00220 Rapam_00220

Rapam_00210 : CDS information

close this sectionLocation

Organism
StrainNRRL 5491
Entry nameRapamycin
Contig
Start / Stop / Direction96,465 / 97,625 / + [in whole cluster]
96,465 / 97,625 / + [in contig]
Location96465..97625 [in whole cluster]
96465..97625 [in contig]
TypeCDS
Length1,161 bp (386 aa)
Click on the icon to see Genetic map.

close this sectionAnnotation

Category3.3 modification reduction
Productcytochrome P450
Product (GenBank)cytochrome P450
Gene
Gene (GenBank)rapJ
EC number
Keyword
  • C-9 keto group formation
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。
RapJ: Cytochrome P450

rapJとrapNの遺伝子産物はcytochrome P450 enzymesに似ており、C-9 and C-27 (and possibly also C-26 or C-32)をhydroxylateするかもしれない。

---
[PMID: 8635730](1996)
PKS flanking genesの配列解析。
RapJとRapNという2つのcytochrome P-450 monooxygenases (P450s)があり、これらはmacrocycleの'late' modificationに関与している可能性がある。

--
[PMID: 11372782](2001)
RapNはC-27でのhydroxylationをすることがdeletion mutantで確認されたので、消去法でRapJがC-9でのhydroxylationをするのかもと言っている。実験はされてない。

--
[PMID: 16990929](2006)
rapKIJMNOQL deletion mutant S.hygroscopicus MG2-10の相補実験で、rapJを含んだ株の産物ではC-9 keto基が見られた。
rapJのみの相補で得られた化合物にはmethoxy基は存在しなかった。
rapJ, rapKJを発現したS.lividans TK24にpre-rapamycin(PKSから放出された後の最初の中間体。未修飾aglycon。)を与えると同じ化合物が得られた。
よって、RapJはC-9 keto基を形成するため、酸素挿入の2ラウンドを実施する驚くべき能力を持つと示唆される。
Related Reference
ACC
P77977
PmId
[8752344] Characterization of methyltransferase and hydroxylase genes involved in the biosynthesis of the immunosuppressants FK506 and FK520. (J Bacteriol. , 1996)
comment
3rd(P77977) 74%, 1e-167
Streptomyces sp.(MA6858)_fkbD
Cyt P-450-9-deoxo-FK506 hydroxylase

[PMID: 8752344](1996)
Disruption mutantを作製して実験している。
fkbDの破壊は下流にあるfkbMの合成にpolar effectを及ぼし、その結果9-deoxo-31-O-demethyl-FK506の形成をもたらす。これはFkbDをcytochrome P-450 9-deoxo-FK506 hydroxylaseとして確立し、それはFK506 and FK520 macrolactone ringのC-9におけるhydroxylationを担う。

close this sectionSequence

selected fasta
>cytochrome P450 [cytochrome P450]
MSTEAQQESTPTARCPFSIQDGHRTILETGTVGAHELFGVKQWLVAAAEDVKLVTNDPRF
SSAAPSGILGDRRPGWFSGMDSPEHNRYRQKIARDFTLRAARKQEEFIVRAADSCLDDIE
ASGPGTDLVPGYAKRLASLAIHDLYGLNEEGPVLEGQMRAMEGGTDMESIKRLTDEFGHV
LALVRAKRDEAGDRLLHRLAESGEDEILLSDEEATGVFATLLFAGHDSMQQMVGYSLYAL
LSHPEQRAALRENPDLIDGAVEELLRFLPLNQLGVPRVCVEDVELHGQTISAGDNVIPLY
STANRDPGVFADPDTFDITRKPEHNFAFGYGIHGCPGQHLARVLIKVATVRLFERFPDVR
LAGDVPMNEGLGLFSPAELRVTWGAE
selected fasta
>cytochrome P450 [cytochrome P450]
ATGAGCACCGAAGCTCAGCAAGAGAGCACGCCCACCGCACGCTGCCCCTTCTCGATCCAG
GACGGGCACCGCACGATCCTGGAGACCGGCACGGTCGGCGCGCACGAACTCTTCGGCGTC
AAGCAATGGCTGGTGGCCGCGGCCGAGGACGTCAAGCTGGTCACCAACGACCCCCGGTTC
AGCTCGGCGGCGCCGTCCGGGATACTCGGCGACCGGCGGCCGGGCTGGTTCTCCGGGATG
GACTCGCCGGAGCACAACCGCTATCGGCAGAAGATCGCCCGGGACTTCACCCTGCGGGCC
GCGCGCAAGCAGGAGGAGTTCATCGTCCGGGCGGCGGACTCCTGCCTCGACGACATCGAG
GCGTCCGGTCCCGGCACCGATCTGGTTCCCGGGTACGCCAAGCGCCTGGCGTCCCTGGCC
ATCCACGACCTCTACGGCCTGAATGAGGAGGGGCCCGTACTCGAGGGCCAGATGCGGGCC
ATGGAGGGCGGCACCGACATGGAGAGCATCAAGAGGCTGACCGACGAATTCGGTCACGTC
CTGGCGCTGGTGCGTGCCAAGCGGGACGAGGCGGGCGACAGGCTTCTGCACCGGCTGGCC
GAGTCCGGCGAGGACGAGATCCTGCTCAGCGACGAGGAGGCGACCGGGGTGTTCGCCACT
CTGCTGTTCGCCGGGCACGACTCGATGCAGCAGATGGTCGGCTACAGTCTGTACGCGCTG
CTCTCCCATCCCGAGCAGCGGGCGGCGCTGCGGGAGAACCCGGACCTGATCGACGGCGCG
GTCGAGGAGCTGCTGCGCTTCCTGCCGCTCAACCAGCTCGGCGTGCCGCGGGTCTGTGTC
GAGGACGTCGAGCTGCACGGCCAGACCATCAGCGCCGGCGACAACGTGATCCCGCTCTAC
TCGACGGCCAACCGCGACCCCGGCGTCTTCGCCGACCCCGACACGTTCGACATCACGCGT
AAGCCCGAACACAACTTCGCTTTCGGGTACGGCATCCACGGCTGCCCGGGGCAGCACCTC
GCCCGCGTGTTGATCAAGGTCGCCACCGTGCGCCTGTTCGAGCGCTTCCCGGATGTGCGA
CTGGCGGGCGACGTGCCGATGAACGAGGGTCTGGGCCTGTTCAGCCCGGCCGAGCTCCGG
GTCACCTGGGGAGCGGAGTGA

close this sectionFeature

BLASTP
Database:UniProtKB:2011_09 		show BLAST table
InterPro
Database:interpro:38.0
IPR001128 Cytochrome P450 (Family)
[224-241] 7.89999609889417e-05 PR00385 [259-270] 7.89999609889417e-05 PR00385 [326-335] 7.89999609889417e-05 PR00385 [335-346] 7.89999609889417e-05 PR00385
PR00385   P450
[28-383] 2.30000000000004e-84 G3DSA:1.10.630.10
G3DSA:1.10.630.10   Cyt_P450
[194-356] 4.9e-26 PF00067
PF00067   p450
[16-383] 9.40003071030835e-78 SSF48264
SSF48264   Cytochrome_P450
IPR002397 Cytochrome P450, B-class (Family)
[80-91] 2.60000517657733e-36 PR00359 [127-143] 2.60000517657733e-36 PR00359 [178-200] 2.60000517657733e-36 PR00359 [259-270] 2.60000517657733e-36 PR00359 [277-304] 2.60000517657733e-36 PR00359 [305-320] 2.60000517657733e-36 PR00359 [326-335] 2.60000517657733e-36 PR00359 [335-346] 2.60000517657733e-36 PR00359
PR00359   BP450
IPR017972 Cytochrome P450, conserved site (Conserved_site)
[328-337] PS00086
PS00086   CYTOCHROME_P450
SignalP No significant hit
TMHMM No significant hit
Rapam_00200 Rapam_00200   Rapam_00220 Rapam_00220
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