C1027_00320 C1027_00320   C1027_00340 C1027_00340

C1027_00330 : CDS information

close this sectionLocation

Organism
StrainC-1027
Entry nameC-1027
Contig
Start / Stop / Direction40,981 / 39,362 / - [in whole cluster]
40,981 / 39,362 / - [in contig]
Locationcomplement(39362..40981) [in whole cluster]
complement(39362..40981) [in contig]
TypeCDS
Length1,620 bp (539 aa)
Click on the icon to see Genetic map.

close this sectionAnnotation

Category3.4 other modification
Product4-methylideneimidazole-5-one(MIO)-dependent tyrosine aminomutase
Product (GenBank)putative ammonia lyase/transferase
GenesgcC4
Gene (GenBank)
EC number
Keyword
  • (S)-3-chloro-4,5-dihydroxy-beta-phenylalanine
Note
Note (GenBank)
  • ORF24
Reference
ACC
PmId
[12183628] Biosynthesis of the enediyne antitumor antibiotic C-1027. (Science. , 2002)
[12785829] A novel 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis. (J Am Chem Soc. , 2003)
[14580219] Kinetic analysis of the 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis. (Biochemistry. , 2003)
[16104723] Biosynthesis of the beta-amino acid moiety of the enediyne antitumor antibiotic C-1027 featuring beta-amino acyl-S-carrier protein intermediates. (J Am Chem Soc. , 2005)
[17516659] The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor antibiotic biosynthetic pathway. (Biochemistry. , 2007)
[18078753] Design and characterization of mechanism-based inhibitors for the tyrosine aminomutase SgTAM. (Bioorg Med Chem Lett. , 2008)
[20577998] Probing the active site of MIO-dependent aminomutases, key catalysts in the biosynthesis of beta-amino acids incorporated in secondary metabolites. (Biopolymers. , 2010)
comment
[PMID:12183628]
C-1027の生合成遺伝子クラスターの報告

sgcC to sgcC5, encoding beta-amino biosynthesis.
機能解析はしていない。
aminomutase(SgcC4)としている。


[PMID:12785829]
sgcC4欠損株、C-1027の生産ができなかったことからC-1027の生合成に必須だとしている。
SgcC4をECOで発現、精製。過剰発現株作製。
酵素学的な解析から、SgcC4はl-tyrosineを(S)-beta-tyrosineへ変換する酵素であり、活性部位で4-methylideneimidazole-5-one (MIO)を利用することが証明された。これはborohydride and cyanide inhibition studiesやsite-directed mutagenesisでもサポートされた。S153A mutant はkcat/KMが340-fold decrease。SgcC4はaminomutaseの新規タイプであった。


[PMID:14580219]　abst only
SgcC4はbeta-tyrosine racemase activityも示されたが、alpha-tyrosine racemase activityは検出されなかった。


[PMID:16104723]
SgcC, SgcC1,SgcC2,SgcC3,SgcC4の5段階について各酵素または突然変異体を大腸菌中で過剰発現させ,in vitroおよびin vivo代謝生成物をMALDI-MSにより解析した。sgcC4欠損株は、いかなる産物も産生しなかったことを見ている。


[PMID:17516659]
SgcC4の結晶構造解析

Tyr303、Glu71はhydrogen bondを形成し、active siteへアクセスする溶媒のブロックを寄与することが示された。

[PMID:18078753]　abstract only
tyrosine aminomutase SgTAMの構造解析

[PMID:20577998]
MIO-dependent aminomutases SgTAMの結晶構造解析

Tyr63Phe mutantは、活性なくなった。
Tyr63はcatalytic mechanismに関与する残基であることが示され、L-tyrosineのalpha and beta-hydrogens間のプロトンの移送に関与する事が示された。詳細なメカニズムはさらに検討が必要とのこと。

close this sectionSequence

selected fasta
>4-methylideneimidazole-5-one(MIO)-dependent tyrosine aminomutase [putative ammonia lyase/transferase]
MALTQVETEIVPVSVDGETLTVEAVRRVAEERATVDVPAESIAKAQKSREIFEGIAEQNI
PIYGVTTGYGEMIYMQVDKSKEVELQTNLVRSHSAGVGPLFAEDEARAIVAARLNTLAKG
HSAVRPIILERLAQYLNEGITPAIPEIGSLGASGDLAPLSHVASTLIGEGYVLRDGRPVE
TAQVLAERGIEPLELRFKEGLALINGTSGMTGLGSLVVGRALEQAQQAEIVTALLIEAVR
GSTSPFLAEGHDIARPHEGQIDTAANMRALMRGSGLTVEHADLRRELQKDKEAGKDVQRS
EIYLQKAYSLRAIPQVVGAVRDTLYHARHKLRIELNSANDNPLFFEGKEIFHGANFHGQP
IAFAMDFVTIALTQLGVLAERQINRVLNRHLSYGLPEFLVSGDPGLHSGFAGAQYPATAL
VAENRTIGPASTQSVPSNGDNQDVVSMGLISARNARRVLSNNNKILAVEYLAAAQAVDIS
GRFDGLSPAAKATYEAVRRLVPTLGVDRYMADDIELVADALSRGEFLRAIARETDIQLR
selected fasta
>4-methylideneimidazole-5-one(MIO)-dependent tyrosine aminomutase [putative ammonia lyase/transferase]
ATGGCATTGACTCAAGTCGAGACCGAGATCGTCCCGGTTTCCGTCGACGGCGAGACCCTG
ACCGTCGAAGCCGTACGCCGCGTCGCGGAGGAACGCGCGACGGTCGACGTACCGGCCGAA
TCCATCGCGAAGGCCCAGAAGAGCCGGGAGATCTTCGAAGGGATCGCCGAACAGAACATC
CCCATCTACGGGGTGACCACCGGGTACGGCGAGATGATCTACATGCAGGTCGACAAGTCG
AAGGAAGTCGAACTGCAGACCAATCTCGTCCGTAGCCACAGCGCGGGAGTCGGTCCGCTG
TTCGCCGAGGACGAGGCGCGGGCGATCGTCGCCGCCCGGCTGAACACCCTCGCCAAGGGC
CACTCCGCGGTGCGCCCCATCATCCTCGAACGCCTCGCGCAGTACCTGAACGAGGGCATC
ACCCCGGCCATACCCGAGATCGGGTCACTCGGGGCGAGCGGCGACCTGGCTCCCCTCTCC
CACGTCGCGAGCACCCTCATCGGAGAGGGCTACGTCCTGCGCGACGGACGGCCGGTGGAG
ACCGCCCAGGTGCTGGCCGAGCGGGGCATCGAGCCGCTCGAACTGCGCTTCAAGGAGGGC
CTCGCACTGATCAACGGCACGTCCGGGATGACCGGTCTGGGCTCCCTGGTCGTCGGACGG
GCCCTGGAGCAGGCCCAGCAGGCCGAGATCGTGACGGCTCTGCTCATCGAGGCGGTACGC
GGATCGACCAGCCCCTTCCTCGCGGAGGGGCACGACATAGCCCGCCCGCACGAGGGCCAG
ATCGACACCGCCGCCAACATGCGGGCCCTGATGCGGGGCAGCGGACTGACGGTCGAGCAC
GCCGACCTGCGCCGAGAACTCCAGAAGGACAAGGAGGCCGGCAAGGACGTCCAGCGCTCG
GAGATCTACCTGCAGAAGGCCTACTCGCTGCGGGCCATCCCCCAGGTCGTCGGGGCGGTG
CGCGACACCTTGTACCACGCGCGGCACAAGCTGCGCATCGAGCTCAACTCGGCCAACGAC
AACCCGCTCTTCTTCGAGGGCAAGGAGATCTTCCACGGGGCGAACTTCCACGGTCAGCCG
ATCGCGTTCGCGATGGACTTCGTGACCATCGCGCTCACCCAGCTCGGCGTCCTGGCCGAG
CGGCAGATCAACCGGGTCCTGAACCGGCACCTCAGCTACGGCCTCCCGGAGTTCCTCGTC
TCCGGGGACCCGGGGCTGCACAGCGGATTCGCCGGCGCCCAGTACCCGGCCACCGCACTG
GTGGCCGAGAACCGGACGATCGGCCCGGCCAGCACCCAGAGCGTCCCGTCCAACGGCGAC
AACCAGGACGTGGTGAGCATGGGCCTGATCTCGGCCCGCAACGCCCGCCGGGTCCTGTCG
AACAACAACAAGATCCTCGCGGTGGAGTACCTGGCCGCCGCCCAGGCGGTCGACATCTCC
GGCCGGTTCGACGGCTTGAGCCCGGCGGCGAAGGCCACGTACGAAGCGGTGCGCCGGCTG
GTTCCGACGCTGGGCGTCGACCGGTACATGGCCGACGACATCGAGCTGGTCGCCGACGCG
CTGTCCCGCGGCGAGTTCCTCCGGGCGATCGCCCGGGAGACGGACATCCAGCTGCGCTGA

close this sectionFeature

BLASTP
Database:UniProtKB:2011_09 		show BLAST table
InterPro
Database:interpro:38.0
IPR001106 Aromatic amino acid lyase (Family)
[13-504] PF00221
PF00221   Lyase_aromatic
IPR008948 L-Aspartase-like (Domain)
[12-530] SSF48557
SSF48557   L-Aspartase-like
IPR022313 Phenylalanine/histidine ammonia-lyases, active site (Active_site)
[148-164] PS00488
PS00488   PAL_HISTIDASE
IPR022314 Tyrosine 2,3-aminomutase, putative (Family)
[15-521] TIGR03832
TIGR03832   Tyr_2_3_mutase
IPR024083 L-Aspartase-like, N-terminal (Domain)
[12-206] 1.79999999999997e-69 G3DSA:1.10.275.10
G3DSA:1.10.275.10   G3DSA:1.10.275.10
SignalP No significant hit
TMHMM No significant hit
C1027_00320 C1027_00320   C1027_00340 C1027_00340
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