Herb_00280 Herb_00280   Herb_00300 Herb_00300

Herb_00290 : CDS information

close this sectionLocation

Organism
StrainAM 3672
Entry nameHerbimycin A
Contig
Start / Stop / Direction82,764 / 81,571 / - [in whole cluster]
82,764 / 81,571 / - [in contig]
Locationcomplement(81571..82764) [in whole cluster]
complement(81571..82764) [in contig]
TypeCDS
Length1,194 bp (397 aa)
Click on the icon to see Genetic map.

close this sectionAnnotation

Category3.3 modification reduction
Productputative cytochrome P450
Product (GenBank)HbmP
Gene
Gene (GenBank)hbmP
EC number
Keyword
  • C-4,5 desaturation
Note
Note (GenBank)
  • P450 (PikC subfamily)
Reference
ACC
PmId
[16085885] Insights into the biosynthesis of the benzoquinone ansamycins geldanamycin and herbimycin, obtained by gene sequencing and disruption. (Appl Environ Microbiol. , 2005)
comment
herbimycin生合成系gene clusterのクローニングを行い、同じbenzoquinone ansamycin系のgeldanamycin のgene clusterと比較し、一部の遺伝子欠損株を作成してその生合成における関与を調べた文献。

HbmP(1,194bp):P450

hbmP自体の機能実験は無し。

HbmPに相当するGdm ORFはGdmP。gdmLの不活化はgeldanamycin産生に影響しなかったので、gdm04, gdmPのようなputative oxygenase genesが、geldanamycin と herbimycinに見られるbenzoquinoidとC-4,5二重結合の形成に関連するようだと述べている。
Related Reference
ACC
Q06BL3
NITE
Gelda_00120
PmId
[21979086] Novel 4,5-dihydro-thiazinogeldanamycin in a gdmP mutant strain of Streptomyces hygroscopicus 17997. (Biosci Biotechnol Biochem. , 2011)
[22849774] Identification of 4,5-dihydro-4-hydroxygeldanamycins as shunt products of geldanamycin biosynthesis. (J Nat Prod. , 2012)
[23656556] 19-[(1'S,4'R)-4'-Hydroxy-1'-methoxy-2'-oxopentyl]geldanamycin, a natural geldanamycin analogue from Streptomyces hygroscopicus 17997. (J Nat Prod. , 2013)
comment
Blast 3rd, id94%, 0.0
Streptomyces hygroscopicus 17997_gdmP
GdmP

---
[PMID:21979086](2011)
S.hygroscopicus 17997のgdmP mutantから、4,5-dihydro-geldanamycin と 4,5-dihydro-thiazinogeldanamycin を検出。
後者は中度のanti-HSV-1-virus activityを示し、geldanamycinよりも高い水溶解度を示した。

---
[PMID:22849774](2012)
GdmPはgeldanamycin生合成でdesaturaseとして働くCYP450 oxidaseである（[PMID:18600054] を引用）。

S.hygroscopicus 17997株と、そのgdmP gene disruption mutantの産物を比較。
wild 17997株からのみ、
・(4S)-4,5-dihydro-4-hydroxygeldanamycin
・(4R)-4,5-dihydro-4-hydroxygeldanamycin
を同定した。これら化合物はgeldanamycinより弱い細胞毒性を示す。

また、これら化合物はgdmP mutantでは検出されなかったこと、geldanamycinへの生物変換ができなかったことをふまえ、GdmPによって触媒されるC-4,5 oxidationのshunt産物であるとし、GdmPが触媒するC-4,5 oxidationのschemeを提唱している。

---
[PMID:23656556](2013) abstract
S.hygroscopicus 17997で自然な新規geldanamycin類似体を発見。
gdmP gene disruption mutantでは、その4,5-dihydro型も同定された。
これら化合物はgeldanamycinと比べて、水溶解度が上昇し、HepG2 cellsに対する細胞毒性が減った。

close this sectionSequence

selected fasta
>putative cytochrome P450 [HbmP]
MDEIRDYPELRAAACPFSPPPGYEELRERSAVTRVRMWDGSTPFLVTGYHEARAALGDSR
FSADGTHKAMPRFVKFEVPAEVFNLGRMDDPEHARIRRMLTANFTIRRTEAMRPMIQGIV
DGLLDRLIAQGPPADLVADFAFPLPSQVIGVMLGVSDADFAEFQQASQGVMDFTASAEEM
GAALGVMVDYVTRMCAAKRADPGDDLLSRLIVDQEPTGGLTQQQVVATALVLLLAGHETT
ANMIALSTVLLLNHPDQLARLRADAGLMGNAVDELLRYITIVQEGTGRVAVEDVEVGGVL
IPAGEGVIINLPSANRDPHFADAHELDLSRPNAREHVAFGFGVHQCLGQTLARVELQIAL
ETLLRRLPTLRLEVPLEDLAFLYESMNFGVARVPVAW
selected fasta
>putative cytochrome P450 [HbmP]
ATGGACGAGATACGCGACTACCCCGAATTGCGGGCTGCTGCATGCCCGTTCTCACCCCCG
CCGGGATACGAGGAACTGCGCGAGCGGTCCGCCGTCACGCGGGTGCGGATGTGGGACGGC
AGCACCCCGTTTCTCGTCACCGGCTATCACGAGGCGCGGGCGGCGCTCGGCGACAGCAGG
TTCAGCGCCGACGGCACGCACAAGGCGATGCCCCGCTTTGTGAAGTTCGAGGTGCCGGCC
GAGGTGTTCAACCTCGGGAGGATGGACGATCCGGAGCACGCCCGGATCCGCCGCATGCTC
ACCGCGAACTTCACCATCCGGCGCACCGAGGCGATGCGGCCGATGATCCAGGGCATCGTC
GACGGCCTCCTGGACCGGCTGATCGCCCAGGGCCCGCCGGCCGACCTGGTGGCCGACTTC
GCCTTCCCCCTGCCGTCCCAGGTGATCGGCGTGATGCTGGGGGTCTCGGACGCCGACTTC
GCGGAGTTCCAGCAGGCGTCGCAGGGCGTCATGGACTTCACCGCGTCGGCCGAGGAGATG
GGCGCCGCGCTCGGCGTCATGGTGGACTACGTGACCCGGATGTGCGCGGCCAAGCGCGCC
GACCCGGGCGACGATCTGCTCAGCCGGCTCATCGTCGACCAGGAGCCGACGGGCGGGCTC
ACCCAGCAGCAGGTGGTCGCCACCGCCCTGGTGCTGCTGCTGGCCGGGCACGAGACCACC
GCCAACATGATCGCCCTGTCCACCGTCCTGCTGCTGAACCACCCCGACCAGCTCGCCCGG
CTGCGGGCCGATGCCGGGCTGATGGGCAACGCGGTGGACGAACTGCTCCGGTACATCACG
ATCGTCCAGGAAGGCACCGGACGGGTGGCCGTCGAGGACGTCGAGGTGGGCGGCGTACTC
ATCCCGGCCGGTGAAGGGGTGATCATCAACCTGCCCAGCGCCAACCGGGACCCCCACTTC
GCGGACGCCCACGAGCTGGACCTGAGCCGGCCCAACGCCCGCGAGCATGTCGCGTTCGGC
TTCGGCGTGCACCAGTGCCTGGGGCAGACCCTCGCCCGGGTCGAGCTCCAGATCGCTCTG
GAGACCCTGCTGCGCCGGCTGCCCACGCTGCGCCTGGAGGTCCCGCTCGAGGACCTGGCG
TTTCTGTACGAGTCGATGAACTTCGGCGTCGCCCGTGTGCCCGTCGCCTGGTGA

close this sectionFeature

BLASTP
Database:UniProtKB:2011_09 		show BLAST table
InterPro
Database:interpro:38.0
IPR001128 Cytochrome P450 (Family)
[14-397] 2.19999900980707e-94 SSF48264
SSF48264   Cytochrome_P450
[235-252] 2.19999900980708e-07 PR00385 [270-281] 2.19999900980708e-07 PR00385 [337-346] 2.19999900980708e-07 PR00385 [346-357] 2.19999900980708e-07 PR00385
PR00385   P450
[17-397] 1e-101 G3DSA:1.10.630.10
G3DSA:1.10.630.10   Cyt_P450
[204-367] 4.00000000000001e-27 PF00067
PF00067   p450
IPR002397 Cytochrome P450, B-class (Family)
[88-99] 3.80000697093588e-49 PR00359 [135-151] 3.80000697093588e-49 PR00359 [152-167] 3.80000697093588e-49 PR00359 [189-211] 3.80000697093588e-49 PR00359 [270-281] 3.80000697093588e-49 PR00359 [288-315] 3.80000697093588e-49 PR00359 [337-346] 3.80000697093588e-49 PR00359 [346-357] 3.80000697093588e-49 PR00359
PR00359   BP450
IPR017972 Cytochrome P450, conserved site (Conserved_site)
[339-348] PS00086
PS00086   CYTOCHROME_P450
SignalP No significant hit
TMHMM No significant hit
Herb_00280 Herb_00280   Herb_00300 Herb_00300
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