Mith_00190 Mith_00190   Mith_00210 Mith_00210

Mith_00200 : CDS information

close this sectionLocation

Organism
StrainATCC 12956
Entry nameMithramycin
Contig
Start / Stop / Direction23,168 / 22,425 / - [in whole cluster]
23,168 / 22,425 / - [in contig]
Locationcomplement(22425..23168) [in whole cluster]
complement(22425..23168) [in contig]
TypeCDS
Length744 bp (247 aa)
Click on the icon to see Genetic map.

close this sectionAnnotation

Category2.3 modification addition of sugar moiety
Product4'-keto-D-mycarose C-4' ketoreductase
Product (GenBank)ketoreductase
Gene
Gene (GenBank)mtmTIII
EC number
Keyword
  • D-mycarose
Note
Note (GenBank)
Reference
ACC
PmId
[10102355] Analysis of two chromosomal regions adjacent to genes for a type II polyketide synthase involved in the biosynthesis of the antitumor polyketide mithramycin in Streptomyces argillaceus. (Mol Gen Genet. , 1999)
[11853433] Ketopremithramycins and ketomithramycins, four new aureolic acid-type compounds obtained upon inactivation of two genes involved in the biosynthesis of the deoxysugar moieties of the antitumor drug mithramycin by Streptomyces argillaceus, reveal novel insights into post-PKS tailoring steps of the mithramycin biosynthetic pathway. (J Am Chem Soc. , 2002)
[22997042] Cooperation of two bifunctional enzymes in the biosynthesis and attachment of deoxysugars of the antitumor antibiotic mithramycin. (Angew Chem Int Ed Engl. , 2012)
comment
[PMID: 10102355](1999)
mithramycin PKSの上流・下流に位置する2つの染色体領域のクローニング、シークエンスから、8genesを同定。

mtmTIII はPKSの下流領域に含まれる。他の3genesとは逆向き。
aklaviketone → aklavinone への還元を担うaklaviketone ketoreductasesに最も相同性あり。

mithramycin生合成中間体であるpremithramycinoneはaklaviketoneと同じ相対位置にketo基を持つが、これまでにわかっているmithramycin中間体でこのC-1 keto基は還元されずに保たれているので、MtmTIII の活動の場ではないようだ。このCは4th ringが開環されるときのdecarboxylationで失われるために還元されない。

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[PMID: 11853433](2002)
mtmC and mtmTIII の役割を調査。

mtmTIII の不活化は4E-ketomithramycinの蓄積をもたらし、このketoreductaseがD-mycarose moietyの4-ketoreductionを担うことが示された。

また、配列解析でMtmTIII はpolyketide aglycone生合成に関与したketoreductasesに似ており、deoxysugar生合成に関連したものとはわずかに弱い類似性しかないことから、4-ketosugarがaglyconeに結合されてから還元されると提唱している。

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[PMID:22997042](2012)
MtmC + MtmTIII + MtmGIV + dTDP-4-keto-D-olivose + premithramycin A2 + SAM + NADPH で、premithramycin A3を検出。この反応からMtmTIII and NADPHを除くと、4-keto-D-mycarosyl-premithramycin A2とそのhydrated formを検出。

よって、不活化実験からD-mycarose生合成の4-ketoreductaseとして割り当てられているMtmTIII の機能が確認された。

close this sectionSequence

selected fasta
>4'-keto-D-mycarose C-4' ketoreductase [ketoreductase]
MARTTERALSVVVTGGGSGIGRATARAYAAQGAHVLVVGRTAGHLEETAEGQPRIRAFVA
DLADRDAPERIVAAALDATGGIDVLVNNAAVPWRARLGEIDRERAERQVATNLLGPLFLT
QSAVPHMPAGATVVNISSNPPTRGWPANSVYGSTKVGLDFLTLTWAVELAPRGIRVVSVA
PGPTLTPGLTRARSGQPPRQRDDFSRVPLGRPARPEEIAWWITQVTRQEAGYLTGAVLRV
DGGLSVG
selected fasta
>4'-keto-D-mycarose C-4' ketoreductase [ketoreductase]
GTGGCACGGACGACGGAACGCGCCCTGAGCGTCGTCGTCACCGGCGGTGGTTCCGGCATC
GGCCGGGCCACCGCCCGTGCGTACGCCGCCCAAGGCGCACACGTGCTGGTCGTGGGGCGG
ACCGCCGGGCATCTGGAGGAGACCGCCGAGGGGCAGCCGCGCATTCGGGCGTTCGTCGCC
GACCTCGCCGACCGCGACGCTCCCGAGCGGATCGTGGCGGCGGCGCTGGACGCCACCGGC
GGGATCGACGTCCTGGTCAACAACGCCGCCGTCCCGTGGCGCGCCCGGCTCGGGGAGATC
GACCGGGAGCGCGCCGAGCGGCAGGTCGCCACCAACCTGCTGGGCCCGCTGTTCCTGACC
CAGAGCGCGGTGCCGCACATGCCGGCCGGCGCGACGGTGGTCAACATCAGCTCCAACCCG
CCGACGCGCGGCTGGCCGGCCAACTCGGTCTACGGCAGCACCAAGGTCGGCCTGGACTTC
CTCACCCTCACCTGGGCCGTGGAGCTGGCGCCGCGCGGGATCAGAGTCGTCTCGGTGGCT
CCGGGGCCAACGCTGACCCCGGGCCTCACCCGGGCCAGGTCCGGCCAGCCGCCTCGGCAG
CGCGACGACTTCTCCCGCGTCCCGCTGGGCCGCCCCGCCCGGCCGGAGGAGATCGCCTGG
TGGATCACCCAGGTGACCCGTCAGGAGGCCGGCTATCTGACCGGTGCGGTGCTGCGCGTC
GATGGCGGCCTGAGCGTGGGCTGA

close this sectionFeature

BLASTP
Database:UniProtKB:2011_09 		show BLAST table
InterPro
Database:interpro:38.0
IPR002198 Short-chain dehydrogenase/reductase SDR (Family)
[80-91] 6.99999965558827e-07 PR00080 [131-139] 6.99999965558827e-07 PR00080 [151-170] 6.99999965558827e-07 PR00080
PR00080   SDRFAMILY
[10-169] 2.7e-28 PF00106
PF00106   adh_short
IPR002347 Glucose/ribitol dehydrogenase (Family)
[10-27] 5.29999657550189e-25 PR00081 [80-91] 5.29999657550189e-25 PR00081 [151-170] 5.29999657550189e-25 PR00081 [172-189] 5.29999657550189e-25 PR00081 [208-228] 5.29999657550189e-25 PR00081
PR00081   GDHRDH
IPR016040 NAD(P)-binding domain (Domain)
[11-246] 1.29999999999998e-71 G3DSA:3.40.50.720
G3DSA:3.40.50.720   NAD(P)-bd
IPR020904 Short-chain dehydrogenase/reductase, conserved site (Conserved_site)
[138-166] PS00061
PS00061   ADH_SHORT
SignalP No significant hit
TMHMM No significant hit
Mith_00190 Mith_00190   Mith_00210 Mith_00210
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