A0A1B4XBH3 · SDNO_SORAA
- ProteinHighly reducing polyketide synthase sdnO
- GenesdnO
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids3084 (go to sequence)
- Protein existenceInferred from homology
- Annotation score3/5
Function
function
Highly reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of sordarin and hypoxysordarin, glycoside antibiotics with a unique tetracyclic diterpene aglycone structure (PubMed:27072286).
First, the geranylgeranyl diphosphate synthase sdnC constructs GGDP from farnesyl diphosphate and isopentenyl diphosphate (PubMed:27072286).
The diterpene cyclase sdnA then catalyzes the cyclization of GGDP to afford cycloaraneosene (PubMed:27072286).
Cycloaraneosene is then hydroxylated four times by the putative cytochrome P450 monooxygenases sdnB, sdnE, sdnF and sdnH to give a hydroxylated cycloaraneosene derivative such as cycloaraneosene-8,9,13,19-tetraol (PubMed:27072286).
Although the order of the hydroxylations is unclear, at least C8, C9 and C13 of the cycloaraneosene skeleton are hydroxylated before the sordaricin formation (PubMed:27072286).
Dehydration of the 13-hydroxy group of the hydroxylated cycloaraneosene derivative might be catalyzed by an unassigned hypothetical protein such as sdnG and sdnP to construct the cyclopentadiene moiety (PubMed:27072286).
The FAD-dependent oxidoreductase sdnN is proposed to catalyze the oxidation at C9 of the hydroxylated cycloaraneosene derivative and also catalyze the Baeyer-Villiger oxidation to give the lactone intermediate (PubMed:27072286).
The presumed lactone intermediate would be hydrolyzed to give an acrolein moiety and a carboxylate moiety (PubMed:27072286).
Then, [4+2]cycloaddition would occur between the acrolein moiety and the cyclopentadiene moiety to give sordaricin (PubMed:27072286).
SdnN might also be involved in the [4+2]cycloaddition after the hypothesized oxidation to accommodate the oxidized product and prompt the [4+2]cycloaddition (PubMed:27072286).
GDP-6-deoxy-D-altrose may be biosynthesized from GDP-D-mannose by the putative GDP-mannose-4,6-dehydratase sdnI and the short-chain dehydrogenase sdnK (PubMed:27072286).
The glycosyltransferase sdnJ catalyzes the attachment of 6-deoxy-D-altrose onto the 19-hydroxy group of sordaricin to give 4'-O-demethylsordarin (PubMed:27072286).
The methyltransferase sdnD would complete the biosynthesis of sordarin (PubMed:27072286).
Sordarin can be further modified into hypoxysordarin (PubMed:27072286).
The unique acyl chain at the 3'-hydroxy group of hypoxysordarin would be constructed by an iterative type I PKS sdnO and the trans-acting polyketide methyltransferase sdnL. SdnL would be responsible for the introduction of an alpha-methyl group of the polyketide chain (PubMed:27072286).
Alternatively, the putative beta-lactamase-like sdnR might be responsible for the cleavage and transfer of the polyketide chain from the PKS sdnO to sordarin (PubMed:27072286).
Two putative cytochrome P450 monooxygenases, sdnQ and sdnT, might catalyze the epoxidations of the polyketide chain to complete the biosynthesis of hypoxysordarin (PubMed:27072286).
Transcriptional regulators sdnM and sdnS are presumably encoded for the transcriptional regulation of the expression of the sdn gene cluster (PubMed:27072286).
First, the geranylgeranyl diphosphate synthase sdnC constructs GGDP from farnesyl diphosphate and isopentenyl diphosphate (PubMed:27072286).
The diterpene cyclase sdnA then catalyzes the cyclization of GGDP to afford cycloaraneosene (PubMed:27072286).
Cycloaraneosene is then hydroxylated four times by the putative cytochrome P450 monooxygenases sdnB, sdnE, sdnF and sdnH to give a hydroxylated cycloaraneosene derivative such as cycloaraneosene-8,9,13,19-tetraol (PubMed:27072286).
Although the order of the hydroxylations is unclear, at least C8, C9 and C13 of the cycloaraneosene skeleton are hydroxylated before the sordaricin formation (PubMed:27072286).
Dehydration of the 13-hydroxy group of the hydroxylated cycloaraneosene derivative might be catalyzed by an unassigned hypothetical protein such as sdnG and sdnP to construct the cyclopentadiene moiety (PubMed:27072286).
The FAD-dependent oxidoreductase sdnN is proposed to catalyze the oxidation at C9 of the hydroxylated cycloaraneosene derivative and also catalyze the Baeyer-Villiger oxidation to give the lactone intermediate (PubMed:27072286).
The presumed lactone intermediate would be hydrolyzed to give an acrolein moiety and a carboxylate moiety (PubMed:27072286).
Then, [4+2]cycloaddition would occur between the acrolein moiety and the cyclopentadiene moiety to give sordaricin (PubMed:27072286).
SdnN might also be involved in the [4+2]cycloaddition after the hypothesized oxidation to accommodate the oxidized product and prompt the [4+2]cycloaddition (PubMed:27072286).
GDP-6-deoxy-D-altrose may be biosynthesized from GDP-D-mannose by the putative GDP-mannose-4,6-dehydratase sdnI and the short-chain dehydrogenase sdnK (PubMed:27072286).
The glycosyltransferase sdnJ catalyzes the attachment of 6-deoxy-D-altrose onto the 19-hydroxy group of sordaricin to give 4'-O-demethylsordarin (PubMed:27072286).
The methyltransferase sdnD would complete the biosynthesis of sordarin (PubMed:27072286).
Sordarin can be further modified into hypoxysordarin (PubMed:27072286).
The unique acyl chain at the 3'-hydroxy group of hypoxysordarin would be constructed by an iterative type I PKS sdnO and the trans-acting polyketide methyltransferase sdnL. SdnL would be responsible for the introduction of an alpha-methyl group of the polyketide chain (PubMed:27072286).
Alternatively, the putative beta-lactamase-like sdnR might be responsible for the cleavage and transfer of the polyketide chain from the PKS sdnO to sordarin (PubMed:27072286).
Two putative cytochrome P450 monooxygenases, sdnQ and sdnT, might catalyze the epoxidations of the polyketide chain to complete the biosynthesis of hypoxysordarin (PubMed:27072286).
Transcriptional regulators sdnM and sdnS are presumably encoded for the transcriptional regulation of the expression of the sdn gene cluster (PubMed:27072286).
Pathway
Antibiotic biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 178 | For beta-ketoacyl synthase activity | ||||
Sequence: C | ||||||
Active site | 313 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Active site | 353 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Active site | 632 | For malonyltransferase activity | ||||
Sequence: S | ||||||
Active site | 963 | Proton acceptor; for dehydratase activity | ||||
Sequence: H | ||||||
Active site | 1177 | Proton donor; for dehydratase activity | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | fatty acid synthase activity | |
Molecular Function | oxidoreductase activity | |
Molecular Function | phosphopantetheine binding | |
Biological Process | antibiotic biosynthetic process | |
Biological Process | fatty acid biosynthetic process | |
Biological Process | secondary metabolite biosynthetic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHighly reducing polyketide synthase sdnO
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Sordariomycetes > Sordariomycetidae > Sordariales > Sordariaceae > Sordaria
Accessions
- Primary accessionA0A1B4XBH3
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000441065 | 1-3084 | Highly reducing polyketide synthase sdnO | |||
Sequence: MASPIPLAVVGIACRFPGDATNPEKLWDLLAEGKSAWSRVPSDRWNEEAFLHPSPDDMNGSHNHLGGHFLRQDVGEFDAGFFNVLPGEAAAMDPQQRLLLETTYEAIESAGIPKESLAGSKTAVYMAMFTRDYDRNVYKDMMSIPKYHVTGTGDAILANRISYLFDLRGPSMTIDTGCSGGMAAVAHACQALRSGVSDVALAGAANLILSPDHMVGMSNLHMLNAEGKSYAFDDRGAGYGRGEGIATLVIKRLDDAIKANDPIRAIIRDAAVNQDGHTAGITLPSGQAQEALERQVWSNIGLDPREVGYVEAHGTGTQAGDSAELEGISRVFCRGRTDSESLTVGSIKSNIGHTECVSGLAALIKSILVLEKGAIPPNVNYQTAKPGLDLDKRKLRVPTTLQKWSQPGVPRVSVNSFGYGGTNAHAVLEKAPETQRDSASDSQEDVPRLFTLSAASQSSLQDMAASIAGWVSQERDSQPLPTSRLQDIAYTLSERRSLMAWRFWSVASNEHELVDSLYEASRSTENISKISSSEPPPKISFIFTGQGAQWPGMGRELLQSNAVFAESISRSNKILAGLGAAWGLVDEILRDKGPSRLREAELAQPATTAIQIALVDLARHWGIVPDSVVGHSSGEIAAAYAAGYLSPQQAITAAYYRGFSSAVARSKGLGKGGMLAVGLGEDEVAPYLARISPENGEAVVACQNSPKSVTISGDDAAIAELSELLTKDDVFNRRLLVDTAYHSHHMEAAADEYRSSLGDMEPRNSTGTINMFSSVTGSLKTDDKFDANYWVSNLVGKVRFRDALQALCQHDQTSSSPQTHRVFIEIGPHAALAGPLRQSVADMPTPLPHSYTSALVRGTSASQSALSMAGSLFSRGYPLNISALNSASSLSSSSSPSVIPNLPTYAWDHTKRHWHESRLSRDYRMRKHAYHDLLGLRMTDTTPLRPAWRHMVGVEGLPWLRDHVVDGLIVFPGAGYMCMALQAAEQLALDLPSHSKVKRMRLQNVAFLKGLVIPDSTRERVEVQLVLTPLTGDNGPDNKLGYSFLVTAYTADDDKWTEHCRGSVLIDLVSSSAASSQSTVGFESQHQITYAEAVSSLNLQPGEDIPPSELYQTLRKGGNAYGPTFSGIQVFRLLPDNASEDTSSANVALSTIAIPDIQSIMPAKHMQPHIIHPSTLDVLLHTTLPLVSRRLGVVGSVMPVRIDDLVIDLGEQQLETKTDAQLRAITTLTGSGFRSAEADMLVFPAPSSEVDQGQLMPVISVMGMELRSLAALDGAAAGDPATENLSVEESRDICYEMKWVVDESFLSAEHLVNAVQQRDSSFDTPLERCLGALDKYLGIKALKEFMADLKVLEIAAAGDSNGECTLAFLDALQTRGALPAEYDLTAQPHGDALWQDKYPGVVTVRPLLDSMNHGLDGHYDIVFAAGSLNGSDGVTVQTSLSNIRSLMKPGAVLVAIHDTNSSLSADVFSQTGFNTQLSIPFDELSLTIARAVGSASTTTPVKLQFIAEPGFSTSTSIRTIIDNLPSTLTAKGVQIITAPEPCILNWTKGNLYDQDSDSEPVTLNIVLDNGASPILPTVTNGTPTFSNIVSLLQKQHSKVLWVSLSDDEQHKLNPQKHLITGVARTAHAENELLELVTVDVQQPISESTTSGLVNFLGDIAASFPGLDGAAGETGTKKEREYIYIGENHILVPRVMSSPSLNRQIKKSKETVTSTENFVMTPLKLDIAGKDGPGTAHAATFVEDESHRQPLGEDCVEIQAKAFGVGSSSWASKGRPSSASSIAEYAGVITAIGSGVLISSGLKIGDRVVAWAETSLSFASRPRIPASQVRVLPDHVSLSTGAGLPVSLMTACHALREISNVQPGQVVFIDGAASDIGQAALLVARYLGAKVIVAVSTSDEASFLQDKFGLPLANILPRASPFLRHQLRKLLASGGAIDAILSCAGSAVPGEIIKTQKPFGTLVQVGGTTGAMTASAVNSTVVSLDLGSFLTQTHPSKATRLFDMAMETVHRGLDLEPIRIAYLPMTNLNEALKSARRHENMTKYVVEVGQEAMVKVARPSYILPKLDEHATYVVAGGLGDLGQRFLRLMAKAGARYLVTLSRSGAREGQQSALERELNSLSPLSSLNLLCLKCDVSKEAKIQNSLAEIKAAGFPSVRGVIQASLVLGDSTLDNMTAQDFDRVLQAKAFGTLHLQRVFVPEGLAFFISLSSAVNMIGSAGQANYNAANSLQDALAQFDKSSDCFYMALNIGLIEDATVNSDVIIQSVQRQGLTTIYHDELDAYFEYSLSAEARQAGCHQAVIGFTPESIAKTSIVNGTAKTLMFTHVRRQISKQGQTEDDDAGGASGAVKTFAEFVAQGTHEQDDIEAFAARAIANKLADLMLIEPEDVELDESLNDFGLDSLIAIELRNWIMRELGSPIQTSEVLGSENIWALARKVTLRSVHVTGGAGGDASSTGNSESMARTPSDSSTVPTSIPATPSRSPSREPPAKETLTKSQQHLPIPDLTETLNMLVESRTAIGSLEEKAEIERVIQDFLTTDGPELVEILRSNNDSSSDARLDFYNNHLHLERREPLQDHALFFIGHLAEGEAGAAPPPKHTQAERAAIITGAAMHFKQRLESGSLEQHKLNDIVLCMDTLQWLFHTIQEPGVATDLAQKYPSNNKVVAMRKGHIFEIDVHPEDDYAALHQIFSDIIASSDSSSDSIPKVSVLTTKPRHEWAVLRSQIQSLSPTNAETIDAIESCAFIVSLDHSSPETTSERSTSILLNDLHLSNRWLDKMLTFTVASNGVSSLLGENTMLDGLSARQLSEYMTNEIFTNPKLSPPTSPPASTIRPLLFTLTPHVVETISQQIQHNLSTYHPISSSRHFYSQLNRAFLGSRGMRSKGTVLVAIAMATRLFFGHYEPLWETVTLAKYKQGRIDWLQTLTPDMVAFVDSLIAIHSHSLTSSSEVDWKGMNKLLKEVSISHVQNLQRVADGRGYVEALYSLMGTAISQGHDLPELFKSEAWKQTDRHLSPKRAKTDCLGSGGYLRMQEGGFLMPNPGSLFIHYEVHHRDPLVNVSGREEDVARFEGILGACLGVVRRVVEG | ||||||
Modified residue | 2400 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S |
Keywords
- PTM
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 4-430 | Ketosynthase family 3 (KS3) | ||||
Sequence: PIPLAVVGIACRFPGDATNPEKLWDLLAEGKSAWSRVPSDRWNEEAFLHPSPDDMNGSHNHLGGHFLRQDVGEFDAGFFNVLPGEAAAMDPQQRLLLETTYEAIESAGIPKESLAGSKTAVYMAMFTRDYDRNVYKDMMSIPKYHVTGTGDAILANRISYLFDLRGPSMTIDTGCSGGMAAVAHACQALRSGVSDVALAGAANLILSPDHMVGMSNLHMLNAEGKSYAFDDRGAGYGRGEGIATLVIKRLDDAIKANDPIRAIIRDAAVNQDGHTAGITLPSGQAQEALERQVWSNIGLDPREVGYVEAHGTGTQAGDSAELEGISRVFCRGRTDSESLTVGSIKSNIGHTECVSGLAALIKSILVLEKGAIPPNVNYQTAKPGLDLDKRKLRVPTTLQKWSQPGVPRVSVNSFGYGGTNAHAVLEK | ||||||
Region | 541-841 | Malonyl-CoA:ACP transacylase (MAT) domain | ||||
Sequence: FIFTGQGAQWPGMGRELLQSNAVFAESISRSNKILAGLGAAWGLVDEILRDKGPSRLREAELAQPATTAIQIALVDLARHWGIVPDSVVGHSSGEIAAAYAAGYLSPQQAITAAYYRGFSSAVARSKGLGKGGMLAVGLGEDEVAPYLARISPENGEAVVACQNSPKSVTISGDDAAIAELSELLTKDDVFNRRLLVDTAYHSHHMEAAADEYRSSLGDMEPRNSTGTINMFSSVTGSLKTDDKFDANYWVSNLVGKVRFRDALQALCQHDQTSSSPQTHRVFIEIGPHAALAGPLRQSVA | ||||||
Region | 931-1071 | N-terminal hotdog fold | ||||
Sequence: HDLLGLRMTDTTPLRPAWRHMVGVEGLPWLRDHVVDGLIVFPGAGYMCMALQAAEQLALDLPSHSKVKRMRLQNVAFLKGLVIPDSTRERVEVQLVLTPLTGDNGPDNKLGYSFLVTAYTADDDKWTEHCRGSVLIDLVSS | ||||||
Region | 931-1243 | Dehydratase (DH) domain | ||||
Sequence: HDLLGLRMTDTTPLRPAWRHMVGVEGLPWLRDHVVDGLIVFPGAGYMCMALQAAEQLALDLPSHSKVKRMRLQNVAFLKGLVIPDSTRERVEVQLVLTPLTGDNGPDNKLGYSFLVTAYTADDDKWTEHCRGSVLIDLVSSSAASSQSTVGFESQHQITYAEAVSSLNLQPGEDIPPSELYQTLRKGGNAYGPTFSGIQVFRLLPDNASEDTSSANVALSTIAIPDIQSIMPAKHMQPHIIHPSTLDVLLHTTLPLVSRRLGVVGSVMPVRIDDLVIDLGEQQLETKTDAQLRAITTLTGSGFRSAEADMLVF | ||||||
Domain | 931-1275 | PKS/mFAS DH | ||||
Sequence: HDLLGLRMTDTTPLRPAWRHMVGVEGLPWLRDHVVDGLIVFPGAGYMCMALQAAEQLALDLPSHSKVKRMRLQNVAFLKGLVIPDSTRERVEVQLVLTPLTGDNGPDNKLGYSFLVTAYTADDDKWTEHCRGSVLIDLVSSSAASSQSTVGFESQHQITYAEAVSSLNLQPGEDIPPSELYQTLRKGGNAYGPTFSGIQVFRLLPDNASEDTSSANVALSTIAIPDIQSIMPAKHMQPHIIHPSTLDVLLHTTLPLVSRRLGVVGSVMPVRIDDLVIDLGEQQLETKTDAQLRAITTLTGSGFRSAEADMLVFPAPSSEVDQGQLMPVISVMGMELRSLAALDGA | ||||||
Region | 1099-1275 | C-terminal hotdog fold | ||||
Sequence: LQPGEDIPPSELYQTLRKGGNAYGPTFSGIQVFRLLPDNASEDTSSANVALSTIAIPDIQSIMPAKHMQPHIIHPSTLDVLLHTTLPLVSRRLGVVGSVMPVRIDDLVIDLGEQQLETKTDAQLRAITTLTGSGFRSAEADMLVFPAPSSEVDQGQLMPVISVMGMELRSLAALDGA | ||||||
Region | 1733-2045 | Enoylreductase (ER) domain | ||||
Sequence: GTAHAATFVEDESHRQPLGEDCVEIQAKAFGVGSSSWASKGRPSSASSIAEYAGVITAIGSGVLISSGLKIGDRVVAWAETSLSFASRPRIPASQVRVLPDHVSLSTGAGLPVSLMTACHALREISNVQPGQVVFIDGAASDIGQAALLVARYLGAKVIVAVSTSDEASFLQDKFGLPLANILPRASPFLRHQLRKLLASGGAIDAILSCAGSAVPGEIIKTQKPFGTLVQVGGTTGAMTASAVNSTVVSLDLGSFLTQTHPSKATRLFDMAMETVHRGLDLEPIRIAYLPMTNLNEALKSARRHENMTKYVV | ||||||
Region | 2069-2252 | Catalytic ketoreductase (KRc) domain | ||||
Sequence: ATYVVAGGLGDLGQRFLRLMAKAGARYLVTLSRSGAREGQQSALERELNSLSPLSSLNLLCLKCDVSKEAKIQNSLAEIKAAGFPSVRGVIQASLVLGDSTLDNMTAQDFDRVLQAKAFGTLHLQRVFVPEGLAFFISLSSAVNMIGSAGQANYNAANSLQDALAQFDKSSDCFYMALNIGLIE | ||||||
Domain | 2363-2440 | Carrier | ||||
Sequence: DIEAFAARAIANKLADLMLIEPEDVELDESLNDFGLDSLIAIELRNWIMRELGSPIQTSEVLGSENIWALARKVTLRS | ||||||
Region | 2445-2501 | Disordered | ||||
Sequence: GGAGGDASSTGNSESMARTPSDSSTVPTSIPATPSRSPSREPPAKETLTKSQQHLPI | ||||||
Compositional bias | 2447-2501 | Polar residues | ||||
Sequence: AGGDASSTGNSESMARTPSDSSTVPTSIPATPSRSPSREPPAKETLTKSQQHLPI | ||||||
Region | 2864-3084 | Choline/carnitine acyltransferase domain | ||||
Sequence: HFYSQLNRAFLGSRGMRSKGTVLVAIAMATRLFFGHYEPLWETVTLAKYKQGRIDWLQTLTPDMVAFVDSLIAIHSHSLTSSSEVDWKGMNKLLKEVSISHVQNLQRVADGRGYVEALYSLMGTAISQGHDLPELFKSEAWKQTDRHLSPKRAKTDCLGSGGYLRMQEGGFLMPNPGSLFIHYEVHHRDPLVNVSGREEDVARFEGILGACLGVVRRVVEG |
Domain
SdnO consists of a ketosynthase domain, acyltransferase domain, dehydratase domain, unassigned region, enoylreductase domain, beta-ketoreductase domain, acyl carrier protein (ACP) and a choline/carnitine acyltransferase domain (PubMed:27072286).
The polyketide chain might be transferred to the 3'-hydroxy group of sordarin by the putative choline/carnitine acyltransferase domain of SdnO because there is no obvious acyltransferase of the polyketide chain in the sdn cluster (PubMed:27072286).
The polyketide chain might be transferred to the 3'-hydroxy group of sordarin by the putative choline/carnitine acyltransferase domain of SdnO because there is no obvious acyltransferase of the polyketide chain in the sdn cluster (PubMed:27072286).
Family and domain databases
Sequence
- Sequence statusComplete
- Length3,084
- Mass (Da)332,855
- Last updated2016-11-02 v1
- Checksum58126617F0154E48
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 2447-2501 | Polar residues | ||||
Sequence: AGGDASSTGNSESMARTPSDSSTVPTSIPATPSRSPSREPPAKETLTKSQQHLPI |