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Synonyms
octaketide synthase, enediyne pks, plant type iii polyketide synthase, dyne8, enediyne polyketide synthase, aaoks,
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16 malonyl-CoA + 28 H+
16 CoA + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-2-methyl-2,3-dihydro-4H-chromen-4-one + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-5-methyl-2,3-dihydro-4H-chromen-4-one + 16 CO2 + 16 H2O
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8 malonyl-CoA
8 CoA + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-2-methyl-2,3-dihydro-4H-chromen-4-one + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-5-methyl-2,3-dihydro-4H-chromen-4-one + 8 CO2 + H2O
additional information
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8 malonyl-CoA
8 CoA + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-2-methyl-2,3-dihydro-4H-chromen-4-one + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-5-methyl-2,3-dihydro-4H-chromen-4-one + 8 CO2 + H2O
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8 malonyl-CoA
8 CoA + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-2-methyl-2,3-dihydro-4H-chromen-4-one + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-5-methyl-2,3-dihydro-4H-chromen-4-one + 8 CO2 + H2O
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i.e. SEK4 and SEK4b
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the oktaketide synthase reaction is also catalyzed by chalcone synthase (EC 2.3.1.74) mutant T197G/G256L/S338V, CHS containing a double point mutation G256L/S338V not only accepts 4coumaroyl-CoA but also biosynthesizes octaketides SEK4 and 4b, exhausting eight malonyl-CoAs
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recombinant oktaketide synthase catalyzes sequential condensations of eight molecules of malonyl-CoA to yield a 1:4 mixture of aromatic octaketides, 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-2-methyl-2,3-dihydro-4H-chromen-4-one and 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-5-methyl-2,3-dihydro-4H-chromen-4-one, which are the longest polyketides generated by the structurally simple type III polyketide synthase. Recombinant oktaketide synthase accepts acetyl-CoA, resulting from decarboxylation of malonyl-CoA, as a starter substrate
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enzyme AaOKS, which is related to the chalcone synthase (CHS) gene family, catalyzes the formation of a linear octaketide, solely by using malonyl-CoA as a substrate. Aloesone is formed by spontaneous cyclization of a linear heptaketide chain made from seven malonyl-CoA units
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the plant type III polyketide synthase, oktaketide synthase (OKS) forms a non-reduced linear octaketide
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enzyme DynE8 makes 2, which is proposed to form the dynemicin enediyne and anthraquinone in the presence of accessory enzymes, and heptaene 1 in the presence of its native TE, DynE7. The end product is enediyne 3, synthesis pathway, overview
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enzyme DynE8 makes 2, which is proposed to form the dynemicin enediyne and anthraquinone in the presence of accessory enzymes, and heptaene 1 in the presence of its native TE, DynE7. The end product is enediyne 3, synthesis pathway, overview
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additional information
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enzyme DynE8 makes 2, which is proposed to form the dynemicin enediyne and anthraquinone in the presence of accessory enzymes, and heptaene 1 in the presence of its native TE, DynE7. The end product is enediyne 3, synthesis pathway, overview
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16 malonyl-CoA + 28 H+
16 CoA + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-2-methyl-2,3-dihydro-4H-chromen-4-one + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-5-methyl-2,3-dihydro-4H-chromen-4-one + 16 CO2 + 16 H2O
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8 malonyl-CoA
8 CoA + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-2-methyl-2,3-dihydro-4H-chromen-4-one + 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-5-methyl-2,3-dihydro-4H-chromen-4-one + 8 CO2 + H2O
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additional information
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additional information
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the oktaketide synthase reaction is also catalyzed by chalcone synthase (EC 2.3.1.74) mutant T197G/G256L/S338V, CHS containing a double point mutation G256L/S338V not only accepts 4coumaroyl-CoA but also biosynthesizes octaketides SEK4 and 4b, exhausting eight malonyl-CoAs
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additional information
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enzyme DynE8 makes 2, which is proposed to form the dynemicin enediyne and anthraquinone in the presence of accessory enzymes, and heptaene 1 in the presence of its native TE, DynE7. The end product is enediyne 3, synthesis pathway, overview
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additional information
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enzyme DynE8 makes 2, which is proposed to form the dynemicin enediyne and anthraquinone in the presence of accessory enzymes, and heptaene 1 in the presence of its native TE, DynE7. The end product is enediyne 3, synthesis pathway, overview
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additional information
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enzyme DynE8 makes 2, which is proposed to form the dynemicin enediyne and anthraquinone in the presence of accessory enzymes, and heptaene 1 in the presence of its native TE, DynE7. The end product is enediyne 3, synthesis pathway, overview
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evolution
pentaketide chromone synthase is a plant-specific type III polyketide synthase that belongs to the chalcone synthase superfamily of type III polyketide synthases
evolution
pentaketide chromone synthase is a plant-specific type III polyketide synthase that belongs to the chalcone synthase superfamily of type III polyketide synthases and grouped with other non-chalcone forming enzymes
metabolism
dual role for the octaketide synthase (OKS) in dynemicin enediyne and anthraquinone biosynthesis. An analysis of enediyne PKSs with their cognate thioesterases (TEs) from five different enediyne producers demonstrates production of heptaene 1 as their major product. Mixed-and-matched PKSs and TEs from 9- and 10-membered systems also produce 1, suggesting a convergent model of biosynthesis for this family of natural products. Despite the common production of 1 in enediyne systems, it is eliminated as a possible on-pathway precursor to the enediyne core. The calicheamicin enediyne PKS, CalE8, and the C-1027 TE are shown to make heptaene, but CalE8 is previously demonstrated to not restore antibiotic production in a C-1027 enediyne PKS knockout strain, leading to the conclusion that 1 is a shunt product of enediyne biosynthesis. The programmed product of the enediyne PKS is enzyme-bound beta-hydroxyhexaene 2
metabolism
the enzyme OKS catalyzes the first step in carminic acid biosynthesis. Proposed biosynthetic pathway for formation of carminic acid and the required enzymatic steps. Formation of pathway intermediate flavokermesic acid anthrone can theoretically be achieved via either a one-step or two-step process, overview
metabolism
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dual role for the octaketide synthase (OKS) in dynemicin enediyne and anthraquinone biosynthesis. An analysis of enediyne PKSs with their cognate thioesterases (TEs) from five different enediyne producers demonstrates production of heptaene 1 as their major product. Mixed-and-matched PKSs and TEs from 9- and 10-membered systems also produce 1, suggesting a convergent model of biosynthesis for this family of natural products. Despite the common production of 1 in enediyne systems, it is eliminated as a possible on-pathway precursor to the enediyne core. The calicheamicin enediyne PKS, CalE8, and the C-1027 TE are shown to make heptaene, but CalE8 is previously demonstrated to not restore antibiotic production in a C-1027 enediyne PKS knockout strain, leading to the conclusion that 1 is a shunt product of enediyne biosynthesis. The programmed product of the enediyne PKS is enzyme-bound beta-hydroxyhexaene 2
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physiological function
the oktaketide synthase is involved in the biosynthesis of anthrones and anthraquinones in the medicinal plant
physiological function
the dynemicin enediyne PKS, DynE8, plays a dual role in the biosynthesis of both the enediyne and the anthraquinone halves of the molecule. DynE8 produces the core scaffolds of both the enediyne and anthraquinone
physiological function
together with the C-glucosylated aloesone, aloesin, octaketide anthraquinones, such as aloe emodin occur naturally in Aloe arborescens and their in planta formation is thought to involve a ketoreductase or cyclases that utilize linear octaketides as substrates
physiological function
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the dynemicin enediyne PKS, DynE8, plays a dual role in the biosynthesis of both the enediyne and the anthraquinone halves of the molecule. DynE8 produces the core scaffolds of both the enediyne and anthraquinone
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additional information
active site structure of wild-type and mutant enzymes, overview. Amino acid residue at position 197 in the active site governs the chain length of the polyketide. Leucine at position 256 in the active site for both OKS and PCS influences the substrate preference for malonyl-CoA as a starting unit, while a glycine residue located in the same position and found in the catalytic pocket of chalcone synthase can possibly compel the enzyme to readily accept 4-coumaroyl-CoA as a starting unit
additional information
the critical active-site residue 197, and the catalytic triad, Cys164, His303, and Asn336, are conserved in type III polyketide synthases, while the residues lining the active-site are exchanged to G197, L256, V338 (numbering in Madia sativa CHS). Active-site architecture of pentaketide chromone synthase compared to other type III polhaseyketide synt, crystal structure and hmology modeling, overview
additional information
the enediyne antitumor antibiotics are a family of cytotoxic natural products distinguished by their 9- or 10-membered carbocyclic core structure containing a double bond flanked by two triple bonds
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the enediyne antitumor antibiotics are a family of cytotoxic natural products distinguished by their 9- or 10-membered carbocyclic core structure containing a double bond flanked by two triple bonds
additional information
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the enediyne antitumor antibiotics are a family of cytotoxic natural products distinguished by their 9- or 10-membered carbocyclic core structure containing a double bond flanked by two triple bonds
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G197A
site-directed mutagenesis, the mutant enzyme shows altered activity compared to the wild-type enzyme producing heptaketides
G197T
site-directed mutagenesis, the mutant enzyme shows altered activity compared to the wild-type enzyme producing hexaketides
G197W
site-directed mutagenesis, the mutant enzyme shows altered activity compared to the wild-type enzyme producing tri- and pentaketides
G207A
site-directed mutagenesis, the G207A mutant loses the octaketide-forming activity and yields the heptaketide aloesone in addition to 2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-2-methyl-2,3-dihydro-4H-chromen-4-one/2,7-dihydroxy-5-[(4-hydroxy-2-oxo-2H-pyran-6-yl)methyl]-5-methyl-2,3-dihydro-4H-chromen-4-one
G207F
site-directed mutagenesis, the bulky substitution G207F mutant loses the octaketide-forming activity and yields the pentaketide 2,7-dihydroxy-5-methylchromone
G207L
site-directed mutagenesis, the bulky substitution G207F mutant loses the octaketide-forming activity and yields the pentaketide 2,7-dihydroxy-5-methylchromone
G207M
site-directed mutagenesis, OKS G207M mutant completely loses the octaketide-forming activity, but efficiently produces an unnatural pentaketide, 2,7-dihydroxy-5-methylchromone, from five molecules of malonyl-CoA, not a 5,7-diydroxy-5-methylchromne like the pentaketide chromone synthase, EC 2.3.1.216
G207T
site-directed mutagenesis, the G207T mutant loses the octaketide-forming activity and yields a hexaketide, 6-(2,4-dihydroxy-6-methylphenyl)-4-methoxy-2-pyrone, from six molecules of malonyl-CoA
G207W
site-directed mutagenesis, the mutant loses the octaketide-forming activity and yields a tetraketide, tetracetic acid lactone, along with the triketide, triacetic acid lactone, without the formation of an aromatic ring system
additional information
generation molecularly diverse plant type III polyketides through rational engineering of the oktaketide synthase active site
additional information
oktaketide synthase, EC 2.3.1.OKS, and pentaketide chromone synthase, EC 2.3.1.216, are not functionally interconvertible by the single amino acid switch at residue 207
additional information
biosynthesis of the C-glucosylated anthraquinone, dcII, a precursor for carminic acid, using a combination of enzymes derived from Aloe arborescens, Streptomyces sp. R1128, and the insect Dactylopius coccus. The pathway, which consists of AaOKS, StZhuI, StZhuJ, and DcUGT2, presents an alternative biosynthetic approach for the production of polyketides by using a type III polyketide synthase (PKS) and tailoring enzymes originating from a type II PKS system. Transient expression in Nicotiana benthamiana. Method, detailed overview
additional information
formation of the tricyclic core of carminic acid is achieved via a two-step process wherein a plant type III polyketide synthase (PKS) forms a non-reduced linear octaketide, which subsequently is folded into the desired flavokermesic acid anthrone (FKA) structure by a cyclase and a aromatase from a bacterial type II PKS system. The formed FKA is oxidized to flavokermesic acid and kermesic acid, catalyzed by endogenous A. nidulans monooxygenases, and further converted to dcII and carminic acid by the Dactylopius coccus C-glucosyltransferase DcUGT2. The establishment of a functional biosynthetic carminic acid pathway in Aspergillus nidulans serves as an important step towards industrial-scale production of carminic acid via liquid-state fermentation using a microbial cell factory. Method optimization, overview. Deletion of the gene clusters that are responsible for formation of the major endogenous PKS products in Aspergillus nidulans improves the potential of Aspergillus nidulans as a cell factory for heterologous production of polyketides. Specifically, the gene clusters for production of asperthecin, onodictyphenone, and sterigmatocystin are eliminated as well as the genes responsible for green conidia pigment formation, wA and yA, were eliminated in a non-homologous endjoining defficient Aspergillus nidulans background. Besides the expected lack of conidial pigments, the resulting strain NID2252 does not display any visible effects on morphology and fitness
additional information
individual inactivation of all potential PKS-encoding genes using CRISPR-Cas9 method, the knockouts fail to identify the anthraquinone PKS, identification of dynemicin enediyne PKS, DynE8
additional information
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individual inactivation of all potential PKS-encoding genes using CRISPR-Cas9 method, the knockouts fail to identify the anthraquinone PKS, identification of dynemicin enediyne PKS, DynE8
additional information
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individual inactivation of all potential PKS-encoding genes using CRISPR-Cas9 method, the knockouts fail to identify the anthraquinone PKS, identification of dynemicin enediyne PKS, DynE8
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DNA and amino acid sequence determination and analysis, sequence comparison and phylogenetic analysis
gene pksE, DNA and amino acid sequence determination and analysis
recombinant expression of the gene encoding wild-type enzyme OKS in Aspergillus nidulans strain NID2252 controlled by the Aspergillus nidulans gpdA promoter as a single copy. Construction of a strain co-expressing OKS with ZhuI, which encodes the cyclases that catalyzes formation of the C7-C12 first ring closure. This strain shows 2.5, 2.2, and 2.1fold increases in flavokermesic acid, SEK4, and dehydro-SEK4 levels, respectively, compared to expression of OKS alone. This increase is 60% higher than what is observed with the strains expressing OKS in combination with either ZhuI (UniProt ID Q9F6D3) or ZhuJ (UniProt ID Q9F6D2), respectively, indicating that the cyclase and aromatase, in an additive manner, are able to increase the flux in the artificial de novo pathway towards the desired product, flavokermesic acid
transient functional recombinant expression in Nicotiana benthamiana, coexpression with genes StZhuI and StZhuJ from Streptomyces sp., and DcUGT2 from Dactylopius coccus
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Abe, I.
Engineering of plant polyketide biosynthesis
Chem. Pharm. Bull.
56
1505-1514
2008
Aloe arborescens (Q3L7F5)
brenda
Watanabe, K.; Praseuth, A.P.; Wang, C.C.
A comprehensive and engaging overview of the type III family of polyketide synthases
Curr. Opin. Chem. Biol.
11
279-286
2007
Aloe arborescens (Q3L7F5)
brenda
Lee, Y.S.; Ju, H.K.; Kim, Y.J.; Lim, T.G.; Uddin, M.R.; Kim, Y.B.; Baek, J.H.; Kwon, S.W.; Lee, K.W.; Seo, H.S.; Park, S.U.; Yang, T.J.
Enhancement of anti-inflammatory activity of Aloe vera adventitious root extracts through the alteration of primary and secondary metabolites via salicylic acid elicitation
PLoS ONE
8
e82479
2013
Aloe vera
brenda
Andersen-Ranberg, J.; Kongstad, K.T.; Nafisi, M.; Staerk, D.; Okkels, F.T.; Mortensen, U.H.; Lindberg Moeller, B.; Frandsen, R.J.N.; Kannangara, R.
Synthesis of C-glucosylated octaketide anthraquinones in Nicotiana benthamiana by using a multispecies-based biosynthetic pathway
ChemBioChem
18
1893-1897
2017
Aloe arborescens (Q3L7F5)
brenda
Cohen, D.; Townsend, C.
A dual role for a polyketide synthase in dynemicin enediyne and anthraquinone biosynthesis
Nat. Chem.
10
231-236
2018
Micromonospora chersina (Q84HI8), Micromonospora chersina, Micromonospora chersina NRRL B-24756 (Q84HI8)
brenda
Frandsen, R.J.N.; Khorsand-Jamal, P.; Kongstad, K.T.; Nafisi, M.; Kannangara, R.M.; Staerk, D.; Okkels, F.T.; Binderup, K.; Madsen, B.; Moller, B.L.; Thrane, U.; Mortensen, U.H.
Heterologous production of the widely used natural food colorant carminic acid in Aspergillus nidulans
Sci. Rep.
8
12853
2018
Aloe arborescens (Q3L7F5)
brenda