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Supplementary Data 1: Truncated now marks true 128-token cap hits

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data/Supplementary_Data/Supplementary_Data_1_expert_curation.csv CHANGED
@@ -74,7 +74,7 @@
74
  "73","GFSG_STRHA","278","0.2027","no","not-Yes","3","More specific","More informative","yes","Methylase required for synthesis of the 16-membered macrolide antibiotics FD-891 and FD-892. In vitro uses S-adenosyl-L-methionine to methylate a number of biosynthetic intermediates in the synthesis of FD-891.","O-methyltransferase; part of the gene cluster that mediates the biosynthesis of the mycotoxin citrinin, a hepato-nephrotoxic compound to humans due to inhibition of respiration complex III. The pathway begins with the synthesis of a keto-aldehyde intermediate by the citrinin PKS (pksCT) from successive condensations of 4 malonyl-CoA units, presumably with a simple acetyl-CoA starter unit. Release of the keto-aldehyde intermediate is consistent with the presence of the C-terminal reductive release domain. pksCT is also able to catalyze the reverse reaction, i.e. catalyze the","Share mechanism and process, but differ in substrate specificty and product."
75
  "74","PAMT_CAPAN","459","0.1402","no","not-Yes","3","Equally specific","Less informative","no","Involved in the biosynthesis of capsaicinoids natural products, pungent alkaloids synthesized from phenylpropanoid intermediates in the placental tissue of chili pepper fruit acting as repellant on herbivorous mammals and conferring spiciness to hot peppers. Can transfer an amine from vanillylamine to pyruvate forming vanillin and L-alanine.","Catalyzes the transfer of the alpha-amino group from S- adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). It is the only aminotransferase known to use SAM as an amino donor.","Both aminotransferases, share same cofactor, but differ in role."
76
  "75","FDHA2_METMP","676","0.258","no","Yes","5","Equally specific","Less informative","no","Catalyzes the oxidation of formate to carbon dioxide, with coenzyme F420 as the electron acceptor. In vitro can also use methyl viologen as electron acceptor.","Catalyzes the oxidation of formate to carbon dioxide, with coenzyme F420 as the electron acceptor.","Same function description. Swissprot includes additional info on in vitro."
77
- "76","DCI1_PYRO7","280","0.1694","no","not-Yes","1","More specific","More informative","yes","Peroxisomal di-isomerase that is involved in fatty acid metabolism enzyme by converting 3,5-dienoyl-CoAs to the corresponding 2,4-dienoyl-CoAs. Involved in fatty acid beta- oxidation, which is important for lipid droplets degradation and infectious growth.","Enoyl-CoA hydratase; part of the gene clusters that mediate the biosynthesis of the host-selective toxins (HSTs) AF-toxins responsible for Alternaria black spot of strawberry disease by the strawberry pathotype. AF-toxin I and III are valine derivatives of 2,3-dyhydroxy-isovaleric acid and 2-hydroxy-isovaleric acid respectively, while AF II is an isoleucine derivative of 2- hydroxy-valeric acid. These derivatives are bound to a 9,10-epoxy-8-hydroxy-9-methyl-decatrienoic acid",""
78
  "77","CHHY1_CAEEL","458","0.2963","no","not-Yes","3","Equally specific","Less informative","no","Endo-beta-galactosaminidase that specifically hydrolyzes chondroitin, releasing GlcUA-beta-(1->3)-GalNAc-beta-(1->4)-GlcUA-beta- (1->3)-GalNAc as the main product. Also hydrolyzes to a lesser extent chondroitin sulfates (CS-A, CS-C) and hyaluronic acid. May regulate the function of chondroitin in cell division.","Hyaluronidase catalyzes the hydrolysis of hyaluronic acid (HA), an anionic, non-sulfated glycosaminoglycan composed of D-glucuronic acid and N-acetyl-D-glucosamine residues (Probable). Hydrolyzes low molecular weight hyaluronan (HA) into smaller fragments that are not biologically active (Probable).","Both glycoside hydrolases, but differ in roles. While substrates overlap, they are different."
79
  "78","MET2_CRYN9","528","0.1585","no","not-Yes","3","More specific","More informative","yes","Commits homoserine to the methionine biosynthesis pathway by catalyzing its O-acetylation.","N-acetyltransferase; part of the gene cluster that mediates the biosynthesis of fusaric acid, a mycotoxin with low to moderate toxicity to animals and humans, but with high phytotoxic properties. L-aspartate is suggested as fusaric acid amino acid precursor that is activated and further processed to O-acetyl-L-homoserine by cluster enzymes aspartate kinase FUB3 and homoserine O-acetyltransferase FUB5, as well as enzymes of the primary metabolism. The polyketide synthase (PKS) FUB1 generates the triketide trans-2-hexenal which is presumptively released by the","Both describe O-acetylation of homoserine by FUB3, but prediction describes it within the pathway, rather than the function being annotated."
80
  "79","MAOM_CRYN9","600","0.177","no","not-Yes","3","Equally specific","Less informative","no","NAD-dependent mitochondrial malic enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate.","This enzyme catalyzes the reversible NADP-dependent decarboxylation of (S)-2- oxoglutarate to succinate and CO(2).","Swissprot describes NAD-dependent, prediction describes NADP-dependent. Both describe decarboxylation within the same context, but mention different reactants."
@@ -151,14 +151,14 @@
151
  "150","AOIO_ASPOR","398","0.2235","no","Yes","3","Equally specific","More informative","yes","O-methyltransferase; part of the gene cluster that mediates the biosynthesis of a methylated derivative of known natural products orthosporin and diaporthin. Does not seem to be involved in the biosynthesis of the identified final product of the pathway and its function has still to be determined.","O-methyltransferase; part of the gene cluster that mediates the biosynthesis of azaphilones, a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibiting a broad range of bioactivities. In the first step, the non-reducing polyketide synthase azaA forms the hexaketide precursor from successive condensations of five malonyl-CoA units, presumably with a simple acetyl-CoA starter unit. The reactive polyketide chain then undergoes a PT- mediated C2-C7 cyclization to afford the aromatic ring and is eventually released as an aldehyde through the R-domain. The","Both are O-methyltransferases, but synthesize different products."
152
  "151","PYLD_METBF","263","0.2364","no","not-Yes","1","Equally specific","Equally informative","yes","Catalyzes the ultimate step of the pyrrolysine biosynthesis pathway by converting the isopeptide (3R)-3-methyl-D-ornithyl-N(6)-L- lysine to the 22nd proteinogenic amino acid. Is able to use surrogate substrates such as (3R)-D-ornithyl-N(6)-L-lysine in vitro.","Bifunctional enzyme that catalyzes two of the steps in the biosynthesis of the branched-chain amino acids (BCAA) leucine, isoleucine and valine. Binds pyridoxal 5'-phosphate (PLP) but does not catalyze its condensation with acetoacetyl-CoA to form 2-acetolactate. Catalyzes the alpha-amination of 2-acetolactate to form (2S,3S)-2,3-dihydroxy-3-methylbutanoate ((2S,3S)-2,3-dihydroxy-3-methylbutanoyl-",""
153
  "152","OLSC_RHITR","281","0.2131","no","not-Yes","1","Equally specific","Less informative","no","Involved in the biosynthesis of ornithine lipids (OLs), which are phosphorus-free membrane lipids. Catalyzes the hydroxylation at the 2 position of the secondary fatty acid of OL. Contributes to symbiotic performance and acid tolerance.","Catalyzes the hydrolysis of long-chain fatty acyl-coenzyme A (acyl-CoA) to yield a fatty acid and an acyl-CoA. This is the first step in the degradation of sphingolipids such as ceramide which contain a long-chain fatty acid chain.","Swissprot describes biosynthesis, but prediction describes hydrolysis. Explicit contradiction."
154
- "153","AURI_STRTU","230","0.2668","no","not-Yes","3","Equally specific","More informative","yes","Methyltransferase involved in the biosynthesis of the antibiotic aureothin, a nitroaryl polyketide metabolite with antifungal, cytotoxic and insecticidal activities. Catalyzes the methylation of demethylluteothin to luteothin (also called deoxyaureothin). Is specific for its gamma- pyrone substrate, and does not act on the alpha-pyrone isomer.","O-methyltransferase; part of the gene cluster that mediates the biosynthesis of the meroterpenoids arthripenoids. The first step of the pathway is the synthesis of 6-methylsalicylic acid methyl ester (6-MSAME) by the polyketide synthase aumA. 6-MSAME is then converted to protoarthripenoid A by the cytochrome P450 monooxygenase aumB. Protoarthripenoid A is further oxidized to arthripenoid A by the cytochrome P450 monooxygenase aumC. The FAD-dependent monooxygenase aumD","Both are methyltransferases with same substrate class, but differ in role. and pathway."
155
  "154","SMOA_AGRFC","174","0.1901","no","not-Yes","4","Equally specific","Less informative","no","Part of the sulfoquinovose monooxygenase (sulfo-SMO) pathway, a D-sulfoquinovose degradation pathway that enables the complete utilization of all carbons within sulfoquinovose (SQ) with concomitant production of inorganic sulfite. Catalyzes the NADH- dependent reduction of FMN. FMNH(2) is then transferred to the sulfoquinovose monooxygenase SmoC.","Catalyzes the reduction of FMN to FMNH2 which is then used to reduce pyrimidine N(1)- mononucleotide (mN(1)N) to give pyrimidine N(1)- nucleoside. Can also reduce pyrimidine N(3)- mononucleotide (mN(3)N) to pyrimidine N(3)-nucleotide (N(3)N).","Only differ in downstream (secondary) fate of the product."
156
  "155","BGLR_STRA5","599","0.2347","no","not-Yes","1","Equally specific","Less informative","yes","Displays beta-glucuronidase activity with the artificial substrate p-nitrophenyl-beta-D-glucuronide (PNPG). Is likely capable of scavenging glucuronate from a range of chemically distinct xenobiotic and endobiotic glucuronides present in the gastrointestinal (GI) tract, to be able to utilize these diverse sources of carbon. As part of the GI microbiome, this enzyme would be able to reactivate glucuronide drug conjugates, such reactivated compounds can significantly damage the GI tract.","Component of a beta-galactosidase. Acts on galacto-beta-(1->3)-galacto-beta-(1->6)-galacto-beta-(1->4)-D-galactose (lacto-triose), galacto-beta-(1->4)-galacto-beta-(1->6)-galacto-beta-(1->4)-D-galactose (lacto-tetraose) and galacto-beta-(1->6)-galacto-beta-(1",""
157
  "156","WBGN_ECOLX","290","0.2035","no","not-Yes","1","Equally specific","Less informative","no","Involved in the biosynthesis of the lipopolysaccharide (LPS) O-antigen region. Catalyzes the transfer of colitose from GDP-colitose to the galactose residue of beta-Gal-(1->3)-GlcNAc (lacto-N-biose) via an alpha1,2-linkage. Is specific for beta-Gal-(1->3)-GlcNAc, but can use GDP-L-fucose as the sugar donor with almost the same efficiency as GDP-L-colitose.","Involved in the biosynthesis of 3-deoxy-D-manno-octulosonate (Kdo). Catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to the 3-keto-group of 2-keto-3-deoxy-D-gluconate, yielding 2,3-diketo-2-deoxy-D-gluconate (Kdo).",""
158
  "157","CHNC_ACISS","300","0.2885","no","not-Yes","1","Equally specific","More informative","yes","Hydrolase involved in the degradation of cyclohexanol to adipate. Catalyzes the conversion of hexano-6-lactone (epsilon-caprolactone) to 6-hydroxyhexanoate (Probable).","Acyltransferase; part of the Fusarium detoxification of benzoxazolinone cluster 2 (FDB2) involved in the degradation of benzoxazolinones produced by the host plant. Maize, wheat, and rye produce the 2 benzoxazinone phytoanticipins 2,4-dihy-droxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) that, due to their inherent instability once released, spontaneously degrade to",""
159
  "158","CHND_ACISS","352","0.2422","no","not-Yes","3","Less specific","Equally informative","no","Dehydrogenase involved in the degradation of cyclohexanol to adipate. Catalyzes the conversion of 6- hydroxyhexanoate to 6-oxohexanoate.","Catalyzes the NAD(P)H-dependent reduction of a range of aldehydes and ketones. In vitro also catalyzes the reduction of 4-nitrobenzaldehyde to 4-aminobenzoate.","Both describe the same reversible reaction, but different directions."
160
  "159","LIPA_PENCY","285","0.2466","no","Yes","4","Equally specific","More informative","yes","Secreted alkaline lipase that hydrolyzes acylglycerol lipids such as triacylglycerols and consequently releases free fatty acid. Is able to hydrolyze tributyrin (1,2,3-tributyryl- glycerin).","Secreted lipase involved in Dandruff and seborrheic dermatitis (D/SD) probably via lipase-mediated breakdown of sebaceous lipids and release of irritating free fatty acids. Shows activity against monoglyceride and diglyceride substrates, but not triolein. Able to cleave oleic acid from 1,2-dioleoyl-sn-glycero-3-phosphocholine (18:2-POPC), a major component of cell membranes. Has no activity against 1,2-dioleoyl-sn-glycero-3-phosphoethanol","Both secreted lipases acting on glycerol-based lipids, but highlight different substrate specificites."
161
- "160","BMP2_PSEL2","406","0.2131","no","not-Yes","1","Equally specific","More informative","yes","Brominase involved in the biosynthesis of polybrominated aromatic organic compounds. Catalyzes three successive rounds of bromination of pyrrolyl-S-Bmp1 to produce mono-, di- and tribromopyrrolyl-S-Bmp1.","Involved in the biosynthesis of the siderophore enterobactin (enterochelin), which is a macrocyclic trimeric lactone of N-(2,3- dihydroxymalonyl)-L-aspartate. Catalyzes the transfer of a phenylacetyl moiety from L-phenylacetyl-S-adenosylmethionine (PS-AdoMet) to 3,4-dihydroxybenzoate (3,4-DHB) to generate 4,5-dihydroxybenzoate (4,5-DHB). Can use L-phenylacetyl-S-adenosylmethionine (PS-A",""
162
  "161","ZBD1_GIBM7","364","0.146","no","not-Yes","3","Equally specific","Less informative","yes","Zinc-binding dehydrogenase that acts as a genetic repressor of fumonisin production. With the ABC-type transporter ABC3, is involved in tolerance to pyrrocidines, inhibitors of growth of Gibberella moniliformis produced by the competitor fungus Sarocladium zeae. Under pyrrocidine challenge, abundant ZBD1 sequesters zinc, and decreases zinc availability in the cell, thereby inhibiting fumonisin biosynthesis via competitive inhibition of FUM21 (Probable). ZBD1 enzyme is then active and abundantly present in the cytoplasm where its enoyl reductase domain may detoxify pyrrocidine A by reducing its double-bonded lactam ring to yield pyrrocidine B, at which point the ABC-type transporter ABC3 can then effectively pump pyrrocidine B out of the cell (Probable).","Trans-enoyl reductase; part of the gene cluster that mediates the biosynthesis of oxaleimides, cytotoxic compounds containing an unusual disubstituted succinimide moiety. The first step of the pathway is provided by the HR-PKS poxF that serves in a new mode of collaborative biosynthesis with the PKS-NRPS poxE, by providing the olefin containing amino acid substrate via the synthesis of an ACP- bound dec-4-enoate. The cytochrome P450 monooxygenase poxM-catalyzed oxidation at the alpha-position creates the enzyme-bound 2-hydroxydec-4-enoyl-","Both describe trans-enoyl reductase within fungal secondary metabolism, but they describe different roles."
163
  "162","AACB_ASPA1","375","0.2717","no","Yes","3","Equally specific","Equally informative","yes","N-methyltransferase; part of the gene cluster that mediates the biosynthesis of the diketopiperazine (DKP) aspkyncin. AacB mediates the synthesis of the unnatural amino acid N-methyl-L-alanine via methylation of L-alanine. Aspkyncin is produced by the NRPS aacA via condensation of the two unusual amino-acids N-methyl-L-alanine and L-kynurenine (L-Kyn). N- methyl-L-alanine originates from the methylation of L-alanine by the methyltransferase aacB whereas L-kynurenine is produced by the indoleamine-2,3-dioxygenase (IDO) that catalyzes the ring-opening oxidation of L-Trp to form N-formyl-l-kynurenine, followed by subsequent hydrolyzation to L-kynurenine (L-Kyn) through an endogenous L-kynurenine formamidase (Probable).","N-methyltransferase; part of the gene cluster that mediates the biosynthesis of the tetrahydroxanthone dimer secalonic acid D. The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase AacuL (Probable). The atrochrysone carboxyl ACP thioesterase AacuM then breaks the thioester bond and releases the atrochrysone carboxylic acid from AacuL (Probable). Atrochrysone carboxylic acid is decarboxylated by the decarboxylase AacuI, and oxidized by the anthrone oxygenase AacuG to yield em","Both N-methyltransferases, but differ in product and synthesis pathway."
164
  "163","TPS10_DICPU","356","0.2008","no","not-Yes","4","More specific","Less informative","no","Terpene synthase that converts its substrate farnesyl diphosphate (FPP) into several unidentified sesquiterpenes. TPS10 also converts geranylgeranyl diphosphate (GGPP) into the diterpene beta-araneosene.","Terpene synthase that converts its substrate farnesyl diphosphate (FPP) into the sesquiterpene beta-caryophyllene.","Swissprot mentiones products as unidentified sesquiterpenes, prediction as specific sesquiterpene."
@@ -167,7 +167,7 @@
167
  "166","ISRC_AMPFL","482","0.2161","no","not-Yes","3","Equally specific","Equally informative","yes","Acyltransferase; part of the gene cluster that mediates the biosynthesis of isariins (ISRs), cyclohexadepsipeptides that contain unusual nonproteinogenic amino acid-building blocks and possess a range of antiviral, antibacterial, and other activities. The isariin synthetase isrA possesses six modules but lacks an A domain in module 1. Based on the structures of ISRs, module 1 selects a high saturated polyketide as the starter unit. The PKS isrD probably generates the polyketide residue, which is activated by the CoA ligase isrB, and transferred by the acyltransferase isrC to the PCP1/T1 domain in module 1 (Probable).","O-acyltransferase; part of the gene cluster that mediates the biosynthesis of pyranonigrins, a family of antioxidative compounds. The first step of pyranonigrins biosynthesis is performed by the hybrid PKS-NRPS synthetase that condenses 6 malonyl-CoA units to an acetyl starter unit, to form a 1,3,5-trioxotetradecane-6,8-dienyl-ACP. The enoyl reductase (ER) domain of pynA is likely to be functional during the first two rounds of polyketide chain extension, to generate the saturated C-C","Both describe acyltransferase in BGC, but differ in pathways and products."
168
  "167","P5CR2_AMPFL","313","0.2393","no","not-Yes","3","Less specific","Less informative","yes","Pyrroline-5-carboxylate reductase involved in the biosynthesis of (3S)-methyl-L-proline, one of the building blocks od destruxins (DTXs), cyclohexadepsipeptides that contain unusual nonproteinogenic amino acid-building blocks and possess a range of antiviral, antibacterial, and other activities. The (3S)-methyl-L-proline building block is required for biosynthesis of DTXs including felinotoxins A to E, roseotoxins A to C, [3-Me-Pro] destruxin E chlorohydrin, as well as isaridins (ISDs) B and D. The 2-oxoglutarate-dependent dioxygenase detxE uses L-isoleucine as substrate to produce (4S,5S)-4-methyl-delta1-pyrroline- 5-carboxylate, whereas the pyrroline-5-carboxylate reductases 1 and/or 2 perform the reduction of (4S,5S)-4-methyl-delta1-pyrroline-5- carboxylate to (3S)-methyl-L-proline.","Oxidoreductase; part of the gene cluster that mediates the biosynthesis of the lipopeptide antibiotics leucinostatins that show extensive biological activities, including antimalarial, antiviral, antibacterial, antifungal, and antitumor activities, as well as phytotoxic. Leucinostatin A contains nine amino acid residues, including the unusual amino acid 4-methyl-L-proline (MePro), 2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid (AHyMeOA), 3- hydroxyleucine (HyLeu), alpha-aminoisobutyric acid (AIB),","Both reductases and generally agree on function (although prediction is much less specific), but differ in pathway, role, substrate sub-type."
169
  "168","MAND_DREDA","441","0.1487","no","not-Yes","2","Equally specific","Equally informative","no","Probable endo-1,4-mannanase, a crucial enzyme for depolymerization of seed galactomannans and wood galactoglucomannans. Involved in trapping nematodes.","Endo-1,4-beta-xylanase involved in the hydrolysis of xylan, a major structural heterogeneous polysaccharide found in plant biomass representing the second most abundant polysaccharide in the biosphere, after cellulose.","Both describe endo-acting glycoside hydrolase, but different substrates."
170
- "169","BAM_TRIV3","377","0.178","no","not-Yes","1","More specific","More informative","no","Digests glycogen releasing maltose units.","Alpha-galactosidase that specifically cleaves terminal alpha-1,2-linked galactose residues from N-glycans in glycoproteins. Involved in the degradation of complex N-glycans during N-glycosylation processing. Catalyzes the hydrolysis of terminal alpha-1,2-linked galactose residues from N-glycans in glycoproteins such as alpha-dystroglycan (DAG1), laminin G domain- containing proteins (LMNG1, LMNG2, LMNG3 and LMNG4), transferrin receptor 1 (TFR1) and integrin beta-1 subunit (ITGB1).",""
171
  "170","CEL1_SCLS1","389","0.2009","no","not-Yes","3","More specific","Equally informative","no","Endoglucanase that plays an important role in biomass degradation. Binds onto plant cell walls to participate in the hydrolysis of cellulose.","Endo-1,4-beta-xylanase involved in the hydrolysis of xylan, a major structural heterogeneous polysaccharide found in plant biomass representing the second most abundant polysaccharide in the biosphere, after cellulose.","Both descriptions identify an endo-acting glycoside hydrolase targeting plant cell walls, but differ in target polymers."
172
  "171","FGR4_GIBZE","150","0.1556","no","not-Yes","1","Equally specific","Less informative","yes","Probable cyclase; part of the gene cluster that mediates the biosynthesis of the tetraketides fugralins such as linear fugralin A and cyclic fugralin B, volatile compounds that play a role in the asexual reproductive cycle but are not involved in pathogenicity. Fugralin B is similar to fugralin A except for a cyclization between the carboxylic acid C-8 and the alcohol on C-4 resulting in a six membered lactone ring, probably catalyzed by the cyclase FGR4 (Probable). One of the key features of fugralins is the presence of a double methyl group, which is only rarely encountered in fungal secondary metabolites. As the fugralins cluster does not contain an independent methyltransferase, the PKS FGR1 is probably responsible for adding two methyl groups to the same carbon atom (Probable). The exact role of the individual cluster genes remains unknown and further work is needed to unravel the biosynthetic pathway (Probable).","Scytalone dehydratase-like protein; part of the gene cluster that mediates the biosynthesis of sordarin and hypoxysordarin, glycoside antibiotics with a unique tetracyclic diterpene aglycone structure. First, the geranylgeranyl diphosphate synthase sdnC constructs GGDP from farnesyl diphosphate and isopentenyl diphosphate. The diterpene cyclase sdnA then catalyzes the cyclization of GGDP to afford cycloaraneosene. Cycloaraneosene is then hydroxylated four times by the putative cytochrome P450 monooxygenases sdnB, sdnE, sdnF",""
173
  "172","MPSD_MACPH","396","0.1632","no","Yes","3","Equally specific","Equally informative","yes","Diels-Alderase; part of the gene cluster that mediates the biosynthesis of macrophasetins, 3-decalinoyltetramic acids (DTAs) which feature a tetramate (pyrrolidine-2,4-dione) unit connected to a decalin fragment and that have potent bioactivities. The PKS- NRPS mpsA together with its associated enoylreductase partner mpsG incorporate one unit of acetyl-CoA, seven units of malonyl-CoA, and one unit of L-alanine to assemble the linear tetramic acid intermediate corresponding to the backbone of macrophasetins. Without the Diels-Alderase mpsD, the mpsA/G product can undergo the non-enzymatic intramolecular Diels-Alder (IMDA) reaction to generate both macrophasetin A and macrophasetin B. Catalyzed by mpsD, the linear tetramic acid intermediate is thoroughly converted to macrophasetin A via the endo-IMDA reaction in a regioselective and stereoselective manner. Finally, the cytochrome P450 monooxygenase mpsF catalyzes the hydroxylation at C20 to yield the end product macrophasetin C.","Diels-Alderase; part of the gene cluster that mediates the biosynthesis of oxaleimides, cytotoxic compounds containing an unusual disubstituted succinimide moiety. The first step of the pathway is provided by the HR-PKS poxF that serves in a new mode of collaborative biosynthesis with the PKS-NRPS poxE, by providing the olefin containing amino acid substrate via the synthesis of an ACP- bound dec-4-enoate. The cytochrome P450 monooxygenase poxM-catalyzed oxidation at the alpha-position creates the enzyme-bound 2-hydroxydec-4-","Both Diels-Alderase, agree somewhat on pathway, differ in specific roles."
 
74
  "73","GFSG_STRHA","278","0.2027","no","not-Yes","3","More specific","More informative","yes","Methylase required for synthesis of the 16-membered macrolide antibiotics FD-891 and FD-892. In vitro uses S-adenosyl-L-methionine to methylate a number of biosynthetic intermediates in the synthesis of FD-891.","O-methyltransferase; part of the gene cluster that mediates the biosynthesis of the mycotoxin citrinin, a hepato-nephrotoxic compound to humans due to inhibition of respiration complex III. The pathway begins with the synthesis of a keto-aldehyde intermediate by the citrinin PKS (pksCT) from successive condensations of 4 malonyl-CoA units, presumably with a simple acetyl-CoA starter unit. Release of the keto-aldehyde intermediate is consistent with the presence of the C-terminal reductive release domain. pksCT is also able to catalyze the reverse reaction, i.e. catalyze the","Share mechanism and process, but differ in substrate specificty and product."
75
  "74","PAMT_CAPAN","459","0.1402","no","not-Yes","3","Equally specific","Less informative","no","Involved in the biosynthesis of capsaicinoids natural products, pungent alkaloids synthesized from phenylpropanoid intermediates in the placental tissue of chili pepper fruit acting as repellant on herbivorous mammals and conferring spiciness to hot peppers. Can transfer an amine from vanillylamine to pyruvate forming vanillin and L-alanine.","Catalyzes the transfer of the alpha-amino group from S- adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). It is the only aminotransferase known to use SAM as an amino donor.","Both aminotransferases, share same cofactor, but differ in role."
76
  "75","FDHA2_METMP","676","0.258","no","Yes","5","Equally specific","Less informative","no","Catalyzes the oxidation of formate to carbon dioxide, with coenzyme F420 as the electron acceptor. In vitro can also use methyl viologen as electron acceptor.","Catalyzes the oxidation of formate to carbon dioxide, with coenzyme F420 as the electron acceptor.","Same function description. Swissprot includes additional info on in vitro."
77
+ "76","DCI1_PYRO7","280","0.1694","no","not-Yes","1","More specific","More informative","no","Peroxisomal di-isomerase that is involved in fatty acid metabolism enzyme by converting 3,5-dienoyl-CoAs to the corresponding 2,4-dienoyl-CoAs. Involved in fatty acid beta- oxidation, which is important for lipid droplets degradation and infectious growth.","Enoyl-CoA hydratase; part of the gene clusters that mediate the biosynthesis of the host-selective toxins (HSTs) AF-toxins responsible for Alternaria black spot of strawberry disease by the strawberry pathotype. AF-toxin I and III are valine derivatives of 2,3-dyhydroxy-isovaleric acid and 2-hydroxy-isovaleric acid respectively, while AF II is an isoleucine derivative of 2- hydroxy-valeric acid. These derivatives are bound to a 9,10-epoxy-8-hydroxy-9-methyl-decatrienoic acid",""
78
  "77","CHHY1_CAEEL","458","0.2963","no","not-Yes","3","Equally specific","Less informative","no","Endo-beta-galactosaminidase that specifically hydrolyzes chondroitin, releasing GlcUA-beta-(1->3)-GalNAc-beta-(1->4)-GlcUA-beta- (1->3)-GalNAc as the main product. Also hydrolyzes to a lesser extent chondroitin sulfates (CS-A, CS-C) and hyaluronic acid. May regulate the function of chondroitin in cell division.","Hyaluronidase catalyzes the hydrolysis of hyaluronic acid (HA), an anionic, non-sulfated glycosaminoglycan composed of D-glucuronic acid and N-acetyl-D-glucosamine residues (Probable). Hydrolyzes low molecular weight hyaluronan (HA) into smaller fragments that are not biologically active (Probable).","Both glycoside hydrolases, but differ in roles. While substrates overlap, they are different."
79
  "78","MET2_CRYN9","528","0.1585","no","not-Yes","3","More specific","More informative","yes","Commits homoserine to the methionine biosynthesis pathway by catalyzing its O-acetylation.","N-acetyltransferase; part of the gene cluster that mediates the biosynthesis of fusaric acid, a mycotoxin with low to moderate toxicity to animals and humans, but with high phytotoxic properties. L-aspartate is suggested as fusaric acid amino acid precursor that is activated and further processed to O-acetyl-L-homoserine by cluster enzymes aspartate kinase FUB3 and homoserine O-acetyltransferase FUB5, as well as enzymes of the primary metabolism. The polyketide synthase (PKS) FUB1 generates the triketide trans-2-hexenal which is presumptively released by the","Both describe O-acetylation of homoserine by FUB3, but prediction describes it within the pathway, rather than the function being annotated."
80
  "79","MAOM_CRYN9","600","0.177","no","not-Yes","3","Equally specific","Less informative","no","NAD-dependent mitochondrial malic enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate.","This enzyme catalyzes the reversible NADP-dependent decarboxylation of (S)-2- oxoglutarate to succinate and CO(2).","Swissprot describes NAD-dependent, prediction describes NADP-dependent. Both describe decarboxylation within the same context, but mention different reactants."
 
151
  "150","AOIO_ASPOR","398","0.2235","no","Yes","3","Equally specific","More informative","yes","O-methyltransferase; part of the gene cluster that mediates the biosynthesis of a methylated derivative of known natural products orthosporin and diaporthin. Does not seem to be involved in the biosynthesis of the identified final product of the pathway and its function has still to be determined.","O-methyltransferase; part of the gene cluster that mediates the biosynthesis of azaphilones, a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibiting a broad range of bioactivities. In the first step, the non-reducing polyketide synthase azaA forms the hexaketide precursor from successive condensations of five malonyl-CoA units, presumably with a simple acetyl-CoA starter unit. The reactive polyketide chain then undergoes a PT- mediated C2-C7 cyclization to afford the aromatic ring and is eventually released as an aldehyde through the R-domain. The","Both are O-methyltransferases, but synthesize different products."
152
  "151","PYLD_METBF","263","0.2364","no","not-Yes","1","Equally specific","Equally informative","yes","Catalyzes the ultimate step of the pyrrolysine biosynthesis pathway by converting the isopeptide (3R)-3-methyl-D-ornithyl-N(6)-L- lysine to the 22nd proteinogenic amino acid. Is able to use surrogate substrates such as (3R)-D-ornithyl-N(6)-L-lysine in vitro.","Bifunctional enzyme that catalyzes two of the steps in the biosynthesis of the branched-chain amino acids (BCAA) leucine, isoleucine and valine. Binds pyridoxal 5'-phosphate (PLP) but does not catalyze its condensation with acetoacetyl-CoA to form 2-acetolactate. Catalyzes the alpha-amination of 2-acetolactate to form (2S,3S)-2,3-dihydroxy-3-methylbutanoate ((2S,3S)-2,3-dihydroxy-3-methylbutanoyl-",""
153
  "152","OLSC_RHITR","281","0.2131","no","not-Yes","1","Equally specific","Less informative","no","Involved in the biosynthesis of ornithine lipids (OLs), which are phosphorus-free membrane lipids. Catalyzes the hydroxylation at the 2 position of the secondary fatty acid of OL. Contributes to symbiotic performance and acid tolerance.","Catalyzes the hydrolysis of long-chain fatty acyl-coenzyme A (acyl-CoA) to yield a fatty acid and an acyl-CoA. This is the first step in the degradation of sphingolipids such as ceramide which contain a long-chain fatty acid chain.","Swissprot describes biosynthesis, but prediction describes hydrolysis. Explicit contradiction."
154
+ "153","AURI_STRTU","230","0.2668","no","not-Yes","3","Equally specific","More informative","no","Methyltransferase involved in the biosynthesis of the antibiotic aureothin, a nitroaryl polyketide metabolite with antifungal, cytotoxic and insecticidal activities. Catalyzes the methylation of demethylluteothin to luteothin (also called deoxyaureothin). Is specific for its gamma- pyrone substrate, and does not act on the alpha-pyrone isomer.","O-methyltransferase; part of the gene cluster that mediates the biosynthesis of the meroterpenoids arthripenoids. The first step of the pathway is the synthesis of 6-methylsalicylic acid methyl ester (6-MSAME) by the polyketide synthase aumA. 6-MSAME is then converted to protoarthripenoid A by the cytochrome P450 monooxygenase aumB. Protoarthripenoid A is further oxidized to arthripenoid A by the cytochrome P450 monooxygenase aumC. The FAD-dependent monooxygenase aumD","Both are methyltransferases with same substrate class, but differ in role. and pathway."
155
  "154","SMOA_AGRFC","174","0.1901","no","not-Yes","4","Equally specific","Less informative","no","Part of the sulfoquinovose monooxygenase (sulfo-SMO) pathway, a D-sulfoquinovose degradation pathway that enables the complete utilization of all carbons within sulfoquinovose (SQ) with concomitant production of inorganic sulfite. Catalyzes the NADH- dependent reduction of FMN. FMNH(2) is then transferred to the sulfoquinovose monooxygenase SmoC.","Catalyzes the reduction of FMN to FMNH2 which is then used to reduce pyrimidine N(1)- mononucleotide (mN(1)N) to give pyrimidine N(1)- nucleoside. Can also reduce pyrimidine N(3)- mononucleotide (mN(3)N) to pyrimidine N(3)-nucleotide (N(3)N).","Only differ in downstream (secondary) fate of the product."
156
  "155","BGLR_STRA5","599","0.2347","no","not-Yes","1","Equally specific","Less informative","yes","Displays beta-glucuronidase activity with the artificial substrate p-nitrophenyl-beta-D-glucuronide (PNPG). Is likely capable of scavenging glucuronate from a range of chemically distinct xenobiotic and endobiotic glucuronides present in the gastrointestinal (GI) tract, to be able to utilize these diverse sources of carbon. As part of the GI microbiome, this enzyme would be able to reactivate glucuronide drug conjugates, such reactivated compounds can significantly damage the GI tract.","Component of a beta-galactosidase. Acts on galacto-beta-(1->3)-galacto-beta-(1->6)-galacto-beta-(1->4)-D-galactose (lacto-triose), galacto-beta-(1->4)-galacto-beta-(1->6)-galacto-beta-(1->4)-D-galactose (lacto-tetraose) and galacto-beta-(1->6)-galacto-beta-(1",""
157
  "156","WBGN_ECOLX","290","0.2035","no","not-Yes","1","Equally specific","Less informative","no","Involved in the biosynthesis of the lipopolysaccharide (LPS) O-antigen region. Catalyzes the transfer of colitose from GDP-colitose to the galactose residue of beta-Gal-(1->3)-GlcNAc (lacto-N-biose) via an alpha1,2-linkage. Is specific for beta-Gal-(1->3)-GlcNAc, but can use GDP-L-fucose as the sugar donor with almost the same efficiency as GDP-L-colitose.","Involved in the biosynthesis of 3-deoxy-D-manno-octulosonate (Kdo). Catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to the 3-keto-group of 2-keto-3-deoxy-D-gluconate, yielding 2,3-diketo-2-deoxy-D-gluconate (Kdo).",""
158
  "157","CHNC_ACISS","300","0.2885","no","not-Yes","1","Equally specific","More informative","yes","Hydrolase involved in the degradation of cyclohexanol to adipate. Catalyzes the conversion of hexano-6-lactone (epsilon-caprolactone) to 6-hydroxyhexanoate (Probable).","Acyltransferase; part of the Fusarium detoxification of benzoxazolinone cluster 2 (FDB2) involved in the degradation of benzoxazolinones produced by the host plant. Maize, wheat, and rye produce the 2 benzoxazinone phytoanticipins 2,4-dihy-droxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) that, due to their inherent instability once released, spontaneously degrade to",""
159
  "158","CHND_ACISS","352","0.2422","no","not-Yes","3","Less specific","Equally informative","no","Dehydrogenase involved in the degradation of cyclohexanol to adipate. Catalyzes the conversion of 6- hydroxyhexanoate to 6-oxohexanoate.","Catalyzes the NAD(P)H-dependent reduction of a range of aldehydes and ketones. In vitro also catalyzes the reduction of 4-nitrobenzaldehyde to 4-aminobenzoate.","Both describe the same reversible reaction, but different directions."
160
  "159","LIPA_PENCY","285","0.2466","no","Yes","4","Equally specific","More informative","yes","Secreted alkaline lipase that hydrolyzes acylglycerol lipids such as triacylglycerols and consequently releases free fatty acid. Is able to hydrolyze tributyrin (1,2,3-tributyryl- glycerin).","Secreted lipase involved in Dandruff and seborrheic dermatitis (D/SD) probably via lipase-mediated breakdown of sebaceous lipids and release of irritating free fatty acids. Shows activity against monoglyceride and diglyceride substrates, but not triolein. Able to cleave oleic acid from 1,2-dioleoyl-sn-glycero-3-phosphocholine (18:2-POPC), a major component of cell membranes. Has no activity against 1,2-dioleoyl-sn-glycero-3-phosphoethanol","Both secreted lipases acting on glycerol-based lipids, but highlight different substrate specificites."
161
+ "160","BMP2_PSEL2","406","0.2131","no","not-Yes","1","Equally specific","More informative","no","Brominase involved in the biosynthesis of polybrominated aromatic organic compounds. Catalyzes three successive rounds of bromination of pyrrolyl-S-Bmp1 to produce mono-, di- and tribromopyrrolyl-S-Bmp1.","Involved in the biosynthesis of the siderophore enterobactin (enterochelin), which is a macrocyclic trimeric lactone of N-(2,3- dihydroxymalonyl)-L-aspartate. Catalyzes the transfer of a phenylacetyl moiety from L-phenylacetyl-S-adenosylmethionine (PS-AdoMet) to 3,4-dihydroxybenzoate (3,4-DHB) to generate 4,5-dihydroxybenzoate (4,5-DHB). Can use L-phenylacetyl-S-adenosylmethionine (PS-A",""
162
  "161","ZBD1_GIBM7","364","0.146","no","not-Yes","3","Equally specific","Less informative","yes","Zinc-binding dehydrogenase that acts as a genetic repressor of fumonisin production. With the ABC-type transporter ABC3, is involved in tolerance to pyrrocidines, inhibitors of growth of Gibberella moniliformis produced by the competitor fungus Sarocladium zeae. Under pyrrocidine challenge, abundant ZBD1 sequesters zinc, and decreases zinc availability in the cell, thereby inhibiting fumonisin biosynthesis via competitive inhibition of FUM21 (Probable). ZBD1 enzyme is then active and abundantly present in the cytoplasm where its enoyl reductase domain may detoxify pyrrocidine A by reducing its double-bonded lactam ring to yield pyrrocidine B, at which point the ABC-type transporter ABC3 can then effectively pump pyrrocidine B out of the cell (Probable).","Trans-enoyl reductase; part of the gene cluster that mediates the biosynthesis of oxaleimides, cytotoxic compounds containing an unusual disubstituted succinimide moiety. The first step of the pathway is provided by the HR-PKS poxF that serves in a new mode of collaborative biosynthesis with the PKS-NRPS poxE, by providing the olefin containing amino acid substrate via the synthesis of an ACP- bound dec-4-enoate. The cytochrome P450 monooxygenase poxM-catalyzed oxidation at the alpha-position creates the enzyme-bound 2-hydroxydec-4-enoyl-","Both describe trans-enoyl reductase within fungal secondary metabolism, but they describe different roles."
163
  "162","AACB_ASPA1","375","0.2717","no","Yes","3","Equally specific","Equally informative","yes","N-methyltransferase; part of the gene cluster that mediates the biosynthesis of the diketopiperazine (DKP) aspkyncin. AacB mediates the synthesis of the unnatural amino acid N-methyl-L-alanine via methylation of L-alanine. Aspkyncin is produced by the NRPS aacA via condensation of the two unusual amino-acids N-methyl-L-alanine and L-kynurenine (L-Kyn). N- methyl-L-alanine originates from the methylation of L-alanine by the methyltransferase aacB whereas L-kynurenine is produced by the indoleamine-2,3-dioxygenase (IDO) that catalyzes the ring-opening oxidation of L-Trp to form N-formyl-l-kynurenine, followed by subsequent hydrolyzation to L-kynurenine (L-Kyn) through an endogenous L-kynurenine formamidase (Probable).","N-methyltransferase; part of the gene cluster that mediates the biosynthesis of the tetrahydroxanthone dimer secalonic acid D. The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase AacuL (Probable). The atrochrysone carboxyl ACP thioesterase AacuM then breaks the thioester bond and releases the atrochrysone carboxylic acid from AacuL (Probable). Atrochrysone carboxylic acid is decarboxylated by the decarboxylase AacuI, and oxidized by the anthrone oxygenase AacuG to yield em","Both N-methyltransferases, but differ in product and synthesis pathway."
164
  "163","TPS10_DICPU","356","0.2008","no","not-Yes","4","More specific","Less informative","no","Terpene synthase that converts its substrate farnesyl diphosphate (FPP) into several unidentified sesquiterpenes. TPS10 also converts geranylgeranyl diphosphate (GGPP) into the diterpene beta-araneosene.","Terpene synthase that converts its substrate farnesyl diphosphate (FPP) into the sesquiterpene beta-caryophyllene.","Swissprot mentiones products as unidentified sesquiterpenes, prediction as specific sesquiterpene."
 
167
  "166","ISRC_AMPFL","482","0.2161","no","not-Yes","3","Equally specific","Equally informative","yes","Acyltransferase; part of the gene cluster that mediates the biosynthesis of isariins (ISRs), cyclohexadepsipeptides that contain unusual nonproteinogenic amino acid-building blocks and possess a range of antiviral, antibacterial, and other activities. The isariin synthetase isrA possesses six modules but lacks an A domain in module 1. Based on the structures of ISRs, module 1 selects a high saturated polyketide as the starter unit. The PKS isrD probably generates the polyketide residue, which is activated by the CoA ligase isrB, and transferred by the acyltransferase isrC to the PCP1/T1 domain in module 1 (Probable).","O-acyltransferase; part of the gene cluster that mediates the biosynthesis of pyranonigrins, a family of antioxidative compounds. The first step of pyranonigrins biosynthesis is performed by the hybrid PKS-NRPS synthetase that condenses 6 malonyl-CoA units to an acetyl starter unit, to form a 1,3,5-trioxotetradecane-6,8-dienyl-ACP. The enoyl reductase (ER) domain of pynA is likely to be functional during the first two rounds of polyketide chain extension, to generate the saturated C-C","Both describe acyltransferase in BGC, but differ in pathways and products."
168
  "167","P5CR2_AMPFL","313","0.2393","no","not-Yes","3","Less specific","Less informative","yes","Pyrroline-5-carboxylate reductase involved in the biosynthesis of (3S)-methyl-L-proline, one of the building blocks od destruxins (DTXs), cyclohexadepsipeptides that contain unusual nonproteinogenic amino acid-building blocks and possess a range of antiviral, antibacterial, and other activities. The (3S)-methyl-L-proline building block is required for biosynthesis of DTXs including felinotoxins A to E, roseotoxins A to C, [3-Me-Pro] destruxin E chlorohydrin, as well as isaridins (ISDs) B and D. The 2-oxoglutarate-dependent dioxygenase detxE uses L-isoleucine as substrate to produce (4S,5S)-4-methyl-delta1-pyrroline- 5-carboxylate, whereas the pyrroline-5-carboxylate reductases 1 and/or 2 perform the reduction of (4S,5S)-4-methyl-delta1-pyrroline-5- carboxylate to (3S)-methyl-L-proline.","Oxidoreductase; part of the gene cluster that mediates the biosynthesis of the lipopeptide antibiotics leucinostatins that show extensive biological activities, including antimalarial, antiviral, antibacterial, antifungal, and antitumor activities, as well as phytotoxic. Leucinostatin A contains nine amino acid residues, including the unusual amino acid 4-methyl-L-proline (MePro), 2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid (AHyMeOA), 3- hydroxyleucine (HyLeu), alpha-aminoisobutyric acid (AIB),","Both reductases and generally agree on function (although prediction is much less specific), but differ in pathway, role, substrate sub-type."
169
  "168","MAND_DREDA","441","0.1487","no","not-Yes","2","Equally specific","Equally informative","no","Probable endo-1,4-mannanase, a crucial enzyme for depolymerization of seed galactomannans and wood galactoglucomannans. Involved in trapping nematodes.","Endo-1,4-beta-xylanase involved in the hydrolysis of xylan, a major structural heterogeneous polysaccharide found in plant biomass representing the second most abundant polysaccharide in the biosphere, after cellulose.","Both describe endo-acting glycoside hydrolase, but different substrates."
170
+ "169","BAM_TRIV3","377","0.178","no","not-Yes","1","More specific","More informative","yes","Digests glycogen releasing maltose units.","Alpha-galactosidase that specifically cleaves terminal alpha-1,2-linked galactose residues from N-glycans in glycoproteins. Involved in the degradation of complex N-glycans during N-glycosylation processing. Catalyzes the hydrolysis of terminal alpha-1,2-linked galactose residues from N-glycans in glycoproteins such as alpha-dystroglycan (DAG1), laminin G domain- containing proteins (LMNG1, LMNG2, LMNG3 and LMNG4), transferrin receptor 1 (TFR1) and integrin beta-1 subunit (ITGB1).",""
171
  "170","CEL1_SCLS1","389","0.2009","no","not-Yes","3","More specific","Equally informative","no","Endoglucanase that plays an important role in biomass degradation. Binds onto plant cell walls to participate in the hydrolysis of cellulose.","Endo-1,4-beta-xylanase involved in the hydrolysis of xylan, a major structural heterogeneous polysaccharide found in plant biomass representing the second most abundant polysaccharide in the biosphere, after cellulose.","Both descriptions identify an endo-acting glycoside hydrolase targeting plant cell walls, but differ in target polymers."
172
  "171","FGR4_GIBZE","150","0.1556","no","not-Yes","1","Equally specific","Less informative","yes","Probable cyclase; part of the gene cluster that mediates the biosynthesis of the tetraketides fugralins such as linear fugralin A and cyclic fugralin B, volatile compounds that play a role in the asexual reproductive cycle but are not involved in pathogenicity. Fugralin B is similar to fugralin A except for a cyclization between the carboxylic acid C-8 and the alcohol on C-4 resulting in a six membered lactone ring, probably catalyzed by the cyclase FGR4 (Probable). One of the key features of fugralins is the presence of a double methyl group, which is only rarely encountered in fungal secondary metabolites. As the fugralins cluster does not contain an independent methyltransferase, the PKS FGR1 is probably responsible for adding two methyl groups to the same carbon atom (Probable). The exact role of the individual cluster genes remains unknown and further work is needed to unravel the biosynthetic pathway (Probable).","Scytalone dehydratase-like protein; part of the gene cluster that mediates the biosynthesis of sordarin and hypoxysordarin, glycoside antibiotics with a unique tetracyclic diterpene aglycone structure. First, the geranylgeranyl diphosphate synthase sdnC constructs GGDP from farnesyl diphosphate and isopentenyl diphosphate. The diterpene cyclase sdnA then catalyzes the cyclization of GGDP to afford cycloaraneosene. Cycloaraneosene is then hydroxylated four times by the putative cytochrome P450 monooxygenases sdnB, sdnE, sdnF",""
173
  "172","MPSD_MACPH","396","0.1632","no","Yes","3","Equally specific","Equally informative","yes","Diels-Alderase; part of the gene cluster that mediates the biosynthesis of macrophasetins, 3-decalinoyltetramic acids (DTAs) which feature a tetramate (pyrrolidine-2,4-dione) unit connected to a decalin fragment and that have potent bioactivities. The PKS- NRPS mpsA together with its associated enoylreductase partner mpsG incorporate one unit of acetyl-CoA, seven units of malonyl-CoA, and one unit of L-alanine to assemble the linear tetramic acid intermediate corresponding to the backbone of macrophasetins. Without the Diels-Alderase mpsD, the mpsA/G product can undergo the non-enzymatic intramolecular Diels-Alder (IMDA) reaction to generate both macrophasetin A and macrophasetin B. Catalyzed by mpsD, the linear tetramic acid intermediate is thoroughly converted to macrophasetin A via the endo-IMDA reaction in a regioselective and stereoselective manner. Finally, the cytochrome P450 monooxygenase mpsF catalyzes the hydroxylation at C20 to yield the end product macrophasetin C.","Diels-Alderase; part of the gene cluster that mediates the biosynthesis of oxaleimides, cytotoxic compounds containing an unusual disubstituted succinimide moiety. The first step of the pathway is provided by the HR-PKS poxF that serves in a new mode of collaborative biosynthesis with the PKS-NRPS poxE, by providing the olefin containing amino acid substrate via the synthesis of an ACP- bound dec-4-enoate. The cytochrome P450 monooxygenase poxM-catalyzed oxidation at the alpha-position creates the enzyme-bound 2-hydroxydec-4-","Both Diels-Alderase, agree somewhat on pathway, differ in specific roles."