Calm_00400 Calm_00400   Calm_00420 Calm_00420

Calm_00410 : CDS information

close this sectionLocation

Organism
StrainNRRL 15839
Entry nameCalicheamicin
Contig
Start / Stop / Direction49,636 / 50,997 / + [in whole cluster]
49,636 / 50,997 / + [in contig]
Location49636..50997 [in whole cluster]
49636..50997 [in contig]
TypeCDS
Length1,362 bp (453 aa)
Click on the icon to see Genetic map.

close this sectionAnnotation

Category2.3 modification addition of sugar moiety
ProductNDP-alpha-D-glucose dehydrogenase
Product (GenBank)CalS8
Gene
Gene (GenBank)calS8
EC number1.1.1.-
Keyword
  • aminodideoxypentose
Note
  • dTDP-alpha-D-glucose can be efficiently oxidized.
Note (GenBank)
Reference
ACC
PmId
[12183629] The calicheamicin gene cluster and its iterative type I enediyne PKS. (Science. , 2002)
[12404643] On the origin of deoxypentoses: evidence to support a glucose progenitor in the biosynthesis of calicheamicin. (Chembiochem. , 2002)
[19058170] Natural-product sugar biosynthesis and enzymatic glycodiversification. (Angew Chem Int Ed Engl. , 2008)
[26240141] Structural Characterization of CalS8, a TDP-alpha-D-Glucose Dehydrogenase Involved in Calicheamicin Aminodideoxypentose Biosynthesis. (J Biol Chem. , 2015)
comment
[PMID:12183629]
calicheamicin生合成遺伝子クラスターの報告

このORFは、Fig2の生合成clusterにて、expected production of four unusual activated nucleotide sugars (S1 to S14)と示されているのみ。本文中、特にふれていない。

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[PMID:12404643]
CalS8の機能解析報告。

calS8を大腸菌にて過剰発現させ、精製し機能解析を行っている。
精製酵素のkineticsは他のUDP-alpha-D-glucose dehydrogenase(UDPGlcDH)と一致する一方で、基質としてUDP-alpha-D-glucose と dTDP-alpha-D-glucoseを効率的に利用できることを示した。二次代謝に関与するUDPGlcDHsの中では初めての報告。CalS8はNAD+ dependent。

UDPGlcDHではArgが基質特異性を決定する残基であり、GDPManDHはlysineが保存されているのが特徴。CalS8は、Argに対応するアミノ酸残基がLys340であった。しかし、GDPManDH activityは示さなかった。

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[PMID:19058170]
天然糖の生合成に関する総論

この論文中で、UDP-alpha-D-glucoseから進む2 step(calS8, calS9)はdTDP-sugar pathwayでは前例のない経路であり、その後の4 step(calS14, calS12, calS13, calS10)はdTDP-sugar pathwayでは共通して保存されている経路であるがUDP-sugar生合成にとってはuniqueであると記述している。

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[PMID: 26240141]
CalS8の活性測定と構造解明。
CalS8はUDP-GlcよりもdTDP-Glcを15倍以上好む。

aminopentosyltransferase CalG4での報告と併せてcalicheamicin aminopentose経路がdTDP-sugar-dependentな過程であるという支持は高まるが、CalS9(UDP-alpha-D-glucuronic acid decarboxylase)での報告とは対比する。
Related Reference
ACC
Q0H2W3
PmId
[26289554] Characterization of Early Enzymes Involved in TDP-Aminodideoxypentose Biosynthesis en Route to Indolocarbazole AT2433. (Chembiochem. , 2015)
comment
BLAST id58%
Actinomadura melliaura_atS8(atmS8)
Putative UDP-N-acetyl-D-mannosaminuronic acid dehydrogenase

Actinomadura melliauraにおけるAT2433のaminodideoxypentose生合成に関連する
・dTDP-α-D-glucose dehydrogenase (AtmS8)
・dTDP-α-D-glucuronic acid decarboxylase (AtmS9)
・dTDP-4-keto-α-D-xylose 2,3-dehydratase (AtmS14)
の特徴づけ。

AT2433とcalicheamicinに共通するaminodeoxypentose経路が提唱されている。

close this sectionSequence

selected fasta
>NDP-alpha-D-glucose dehydrogenase [CalS8]
MPFLPDPGEPSPLKVVIAGAGYVGTCLAVTLAGRGAEVVAVDSDPGTVADLRAGRCRLPE
PGLAGAVRDLAATGRLTASTSYDPVGAADVVIVTVGTPTDAGHEMVTDQLVAACEQIAPR
LRAGQLVILKSTVSPGTTRTLVAPLLESGGLVHERDFGLAFCPERLAEGVALAQVRTLPV
VVGGCGPRSAAAAERFWRSALGVDVRQVPSAESAEVVKLATNWWIDANVAIANELARYCA
VLGVDVLDVIGAANTLPKGSSMVNLLLPGVGVGGSCLTKDPWMAWRDGRDRGVPLRTVET
ARAVNDDMPRHTAAVIADELVKLGRDRNDTTIAVLGAAFKNDTGDVRNTPVRGVVAALRD
SGFRVRIFDPLADPAEIVARFGTAPAASLDEAVSGAGCLAFLAGHRQFHELDFGALAERV
DEPCLVFDGRMHLPPARIRELHRFGFAYRGIGR
selected fasta
>NDP-alpha-D-glucose dehydrogenase [CalS8]
ATGCCGTTCCTTCCCGACCCGGGCGAACCGTCCCCGCTGAAGGTGGTCATCGCCGGCGCC
GGCTACGTCGGCACCTGTCTCGCCGTCACCCTCGCCGGCCGCGGCGCCGAGGTGGTCGCG
GTCGACAGCGACCCGGGCACCGTCGCGGACCTGCGGGCCGGCCGGTGCCGGCTGCCCGAG
CCCGGCCTGGCCGGCGCCGTCCGGGACCTCGCCGCGACCGGACGGCTGACGGCGAGCACG
TCGTACGACCCGGTCGGCGCGGCGGACGTGGTGATCGTGACGGTCGGCACCCCGACCGAC
GCCGGCCACGAGATGGTCACCGACCAGCTCGTCGCGGCGTGCGAGCAGATCGCCCCGCGG
CTGCGCGCCGGGCAACTGGTGATCCTCAAGTCGACGGTCTCCCCGGGCACCACCCGGACC
CTCGTCGCGCCCCTGCTGGAGAGCGGCGGGCTGGTGCACGAGCGCGACTTCGGGCTGGCC
TTCTGCCCGGAGCGGCTCGCCGAGGGGGTGGCGCTGGCGCAGGTGCGGACGCTGCCGGTG
GTGGTGGGTGGGTGCGGCCCGCGCAGCGCCGCCGCGGCCGAACGGTTCTGGCGGTCCGCG
CTCGGCGTCGACGTCCGGCAGGTGCCGTCGGCCGAGTCCGCCGAGGTGGTCAAGCTCGCG
ACCAACTGGTGGATCGACGCGAACGTGGCGATCGCCAACGAACTCGCCCGGTACTGCGCG
GTGCTGGGGGTGGACGTCCTCGACGTGATCGGCGCGGCGAACACCCTGCCCAAGGGCAGC
AGCATGGTGAACCTGCTGCTGCCGGGGGTGGGTGTCGGCGGCTCCTGCCTGACGAAGGAC
CCGTGGATGGCGTGGCGGGACGGCCGGGACCGGGGCGTGCCCCTGCGCACGGTCGAGACG
GCCCGCGCGGTCAACGACGACATGCCCCGCCACACCGCCGCCGTCATCGCCGACGAGCTG
GTCAAGCTGGGACGGGATCGGAACGACACGACGATCGCCGTGCTCGGCGCGGCGTTCAAG
AACGACACCGGCGACGTCCGCAACACCCCGGTGCGCGGGGTCGTGGCGGCGCTGCGCGAC
AGCGGCTTCCGGGTCCGGATCTTCGACCCGCTGGCCGATCCCGCCGAGATCGTCGCCCGG
TTCGGCACCGCGCCGGCGGCGAGCCTGGACGAGGCGGTGAGCGGGGCGGGCTGCCTGGCC
TTCCTCGCCGGGCACCGCCAGTTCCACGAGCTCGACTTCGGCGCCCTGGCCGAGCGGGTG
GACGAGCCCTGCCTGGTCTTCGACGGCCGCATGCACCTCCCGCCGGCGCGCATCCGCGAG
CTGCACCGGTTCGGCTTCGCCTACCGCGGCATTGGAAGGTGA

close this sectionFeature

BLASTP
Database:UniProtKB:2011_09 		show BLAST table
InterPro
Database:interpro:38.0
IPR001732 UDP-glucose/GDP-mannose dehydrogenase, N-terminal (Domain)
[14-191] 2.80000000000001e-42 PF03721
PF03721   UDPG_MGDP_dh_N
IPR008927 6-phosphogluconate dehydrogenase, C-terminal-like (Domain)
[211-308] 9.70001793430487e-28 SSF48179
SSF48179   6DGDH_C_like
IPR014026 UDP-glucose/GDP-mannose dehydrogenase, dimerisation (Domain)
[212-308] 1.69999999999999e-19 PF00984
PF00984   UDPG_MGDP_dh
IPR014027 UDP-glucose/GDP-mannose dehydrogenase, C-terminal (Domain)
[333-435] 4.10001399699315e-33 SM00984
SM00984   UDPG_MGDP_dh_C
[333-432] 1.6e-21 PF03720
PF03720   UDPG_MGDP_dh_C
[317-446] 1.39999892049878e-28 SSF52413
SSF52413   UDP-Glc/GDP-Man_DH_C
IPR016040 NAD(P)-binding domain (Domain)
[13-233] 8.60000000000004e-51 G3DSA:3.40.50.720 [243-453] 3.7e-52 G3DSA:3.40.50.720
G3DSA:3.40.50.720   NAD(P)-bd
IPR017476 Nucleotide sugar dehydrogenase (Family)
[4-450] PIRSF000124
PIRSF000124   UDPglc_GDPman_dh
[14-430] 1.39999999999997e-103 TIGR03026
TIGR03026   NDP-sugDHase
SignalP No significant hit
TMHMM No significant hit
Calm_00400 Calm_00400   Calm_00420 Calm_00420
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