asppa-q6ueg5

Aspergillus parasiticus Versiconal hemiacetal acetate esterase aflJ (estA)

Comment

Aspergillus parasiticus || (from Uniprot) Versiconal hemiacetal acetate esterase\; part of the gene cluster that mediates the biosynthesis of aflatoxins, a group of polyketide-derived furanocoumarins, and part of the most toxic and carcinogenic compounds among the known mycotoxins. The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2). The first step of the pathway is the conversion of acetate to norsolorinic acid (NOR) and requires the fatty acid synthase subunits aflA and aflB, as well as the PKS aflC. AflC combines a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor NOR. The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by the fungal fatty acid synthase aflA\/aflB. The second step is the conversion of NOR to averantin (AVN) and requires the norsolorinic acid ketoreductase aflD, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin. The norsolorinic acid reductases aflE and aflF may also play a role in the conversion of NOR to AVN. The cytochrome P450 monooxygenase aflG then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN). The next step is performed by the 5'-hydroxyaverantin dehydrogenase aflH that transforms HAVN to 5'-oxoaverantin (OAVN) which is further converted to averufin (AVF) by aflK that plays a dual role in the pathway, as a 5'-oxoaverantin cyclase that mediates conversion of 5'-oxoaverantin, as well as a versicolorin B synthase in a later step in the pathway. The averufin oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal acetate (VHA). VHA is then the substrate for the versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL). Versicolorin B synthase aflK then converts VAL to versicolorin B (VERB) by closing the bisfuran ring of aflatoxin which is required for DNA-binding, thus giving to aflatoxin its activity as a mutagen. Then, the activity of the versicolorin B desaturase aflL leads to versicolorin A (VERA). A branch point starts from VERB since it can also be converted to dihydrodemethylsterigmatocystin (DMDHST), probably also by aflL, VERA being a precursor for aflatoxins B1 and G1, and DMDHST for aflatoxins B2 and G2. Next, the versicolorin reductase aflM and the cytochrome P450 monooxygenase aflN are involved in conversion of VERA to demethylsterigmatocystin (DMST). AflX and aflY seem also involved in this step, through probable aflX-mediated epoxide ring-opening step following versicolorin A oxidation and aflY-mediated Baeyer-Villiger oxidation required for the formation of the xanthone ring ,. The methyltransferase aflO then leads to the modification of DMST to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin (DHST). Both ST and DHST are then substrates of the O-methyltransferase aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST), respectively. Finally OMST is converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2 and G2, via the action of several enzymes including O-methylsterigmatocystin oxidoreductase aflQ, the cytochrome P450 monooxygenase aflU, but also the NADH-dependent flavin oxidoreductase nadA which is specifically required for the synthesis of AFG1

Relationship

Family : Hormone-sensitive_lipase_like

Block : H

Position in NCBI Life Tree : Aspergillus oryzae

(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)

> cellular organisms N E > Eukaryota N E > Opisthokonta N E > Fungi N E > Dikarya N E > Ascomycota N E > saccharomyceta N E > Pezizomycotina N E > leotiomyceta N E > Eurotiomycetes N E > Eurotiomycetidae N E > Eurotiales N E > Aspergillaceae N E > Aspergillus N E > Aspergillus oryzae N E

Molecular evidence

No mutation

No structure

No kinetic

No disease

No substrate

No inhibitor

Database

Sequence

Peptide

METPFAGPWH QFVEDLGQTP CLPGKDLDSI LAGWGQLAGT LATRYGFPPP DESVATEDVQ LDGLWLRCYT PANATGQEPV GLYFHGGGWV MGGVKEEDGF CRVISRQCQM RLVSVEYRKA PETRYPGALN DGVSAALWAQ SRYENQPLVL MGTSAGGNLA FGTALRLIDQ DMADKVSGVV ALAPITVHPD AVPEHLKEQY TAYEENAELT VNSRAAMQVF FDCYKAPVDD VYTSCLLHPR LLALPKVYIA ELGLDTLRDD ARLMKGALDT AKVPVMYDAY PGYPHCSFMF PFKSLGEHQR TFLGGVAKAV RWMS

References (6)

Title : Deconstruction of iterative multidomain polyketide synthase function - Crawford_2008_Science_320_243
Author(s) : Crawford JM , Thomas PM , Scheerer JR , Vagstad AL , Kelleher NL , Townsend CA
Ref : Science , 320 :243 , 2008
PubMedID: 18403714
Gene_locus related to this paper: aspor-PKSL1 , asppa-q6ueg5

Title : Molecular analysis of an inactive aflatoxin biosynthesis gene cluster in Aspergillus oryzae RIB strains - Tominaga_2006_Appl.Environ.Microbiol_72_484
Author(s) : Tominaga M , Lee YH , Hayashi R , Suzuki Y , Yamada O , Sakamoto K , Gotoh K , Akita O
Ref : Applied Environmental Microbiology , 72 :484 , 2006
PubMedID: 16391082
Gene_locus related to this paper: aspor-PKSL1 , asppa-q6ueg5

Title : The Aspergillus parasiticus estA-encoded esterase converts versiconal hemiacetal acetate to versiconal and versiconol acetate to versiconol in aflatoxin biosynthesis - Chang_2004_Appl.Environ.Microbiol_70_3593
Author(s) : Chang PK , Yabe K , Yu J
Ref : Applied Environmental Microbiology , 70 :3593 , 2004
PubMedID: 15184162
Gene_locus related to this paper: asppa-q6ueg5

Title : Clustered pathway genes in aflatoxin biosynthesis -
Author(s) : Yu J , Chang PK , Ehrlich KC , Cary JW , Bhatnagar D , Cleveland TE , Payne GA , Linz JE , Woloshuk CP , Bennett JW
Ref : Applied Environmental Microbiology , 70 :1253 , 2004
PubMedID: 15006741
Gene_locus related to this paper: aspor-PKSL1 , asppa-q6ueg5

Title : Completed sequence of aflatoxin pathway gene cluster in Aspergillus parasiticus - Yu_2004_FEBS.Lett_564_126
Author(s) : Yu J , Bhatnagar D , Cleveland TE
Ref : FEBS Letters , 564 :126 , 2004
PubMedID: 15094053
Gene_locus related to this paper: aspor-PKSL1 , asppa-q6ueg5

Title : Cloning and functional expression of an esterase gene in Aspergillus parasitcus - Yu_2002_Mycopathologia_156_227
Author(s) : Yu J , Chang PK , Bhatnagar D , Cleveland TE
Ref : Mycopathologia , 156 :227 , 2002
PubMedID: 12749588
Gene_locus related to this paper: asppa-q6ueg5