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Information on EC 2.3.1.240 - narbonolide synthase
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2.3.1.240 narbonolide synthaseIUBMB Comments
The product, narbonolide, contains a 14-membered ring and is an intermediate in the biosynthesis of narbonomycin and pikromycin in the bacterium Streptomyces venezuelae. The enzyme also produces 10-deoxymethynolide (see EC 2.3.1.239, 10-deoxymethynolide synthase). The enzyme has 29 active sites arranged in four polypeptides (pikAI - pikAIV) with a loading domain, six extension modules and a terminal thioesterase domain. Each extension module contains a ketosynthase (KS), keto reductase (KR), an acyltransferase (AT) and an acyl-carrier protein (ACP). Not all active sites are used in the biosynthesis.
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The enzyme appears in viruses and cellular organisms
Reaction Schemes
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6
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5
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5
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7
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7
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5
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2
Synonyms
methymycin/picromycin polyketide synthase, picromycin/methymycin PKS, picromycin/methymycin polyketide synthase, PICS, PikAI, PikAIII, PikAIV, pikromycin PKS, pikromycin polyketide synthase, type I polyketide synthase PikAIV, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
methymycin/picromycin polyketide synthase
-
picromycin/methymycin polyketide synthase
PikAIII
PikAIV
pikromycin PKS
-
-
-
-
pikromycin polyketide synthase
type I polyketide synthase PikAIV
picromycin/methymycin polyketide synthase
-
picromycin/methymycin polyketide synthase
-
-
pikromycin polyketide synthase
-
pikromycin polyketide synthase
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+ = narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+ = narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
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-
-
-
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+ = narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
electron cryo-microscopy (cryo-EM) structures of a full-length polyketide synthase module in three key biochemical states of its catalytic cycle reveals the dynamics of the intramodule acyl carrier protein for sequential binding to catalytic domains within the reaction chamber, and for transferring the elongated and processed polyketide substrate to the next module in the polyketide synthase pathway. During the enzymatic cycle the ketoreductase domain undergoes dramatic conformational rearrangements that enable optimal positioning for reductive processing of the acyl carrier protein-bound polyketide chain elongation intermediate
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+ = narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
electron cryo-microscopy (cryo-EM) structures of a full-length polyketide synthase module in three key biochemical states of its catalytic cycle reveals the dynamics of the intramodule acyl carrier protein for sequential binding to catalytic domains within the reaction chamber, and for transferring the elongated and processed polyketide substrate to the next module in the polyketide synthase pathway. During the enzymatic cycle the ketoreductase domain undergoes dramatic conformational rearrangements that enable optimal positioning for reductive processing of the acyl carrier protein-bound polyketide chain elongation intermediate
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
(2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (narbonolide forming)
The product, narbonolide, contains a 14-membered ring and is an intermediate in the biosynthesis of narbonomycin and pikromycin in the bacterium Streptomyces venezuelae. The enzyme also produces 10-deoxymethynolide (see EC 2.3.1.239, 10-deoxymethynolide synthase). The enzyme has 29 active sites arranged in four polypeptides (pikAI - pikAIV) with a loading domain, six extension modules and a terminal thioesterase domain. Each extension module contains a ketosynthase (KS), keto reductase (KR), an acyltransferase (AT) and an acyl-carrier protein (ACP). Not all active sites are used in the biosynthesis.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(3R,4R,5E,8R,10S,11S,12R)-3-hydroxy-4,8,10,12-tetramethyl-11-[[(2-nitrophenyl)methoxy]methoxy]-13-(phenylsulfanyl)tridec-5-en-7-one + methylmalonyl N-acetylcysteamine
?
(E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate + (2S)-methylmalonyl-CoA + NADPH + H+
narbonolide + ?
hexaketide N-acetyl cysteamine thioester + (2S)-methylmalonyl-CoA + NADPH + H+
narbonolide + ?
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
methylmalonyl-N-acetylcysteamine + S-phenyl (2S,4R,6E,8R,9R)-9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
3-dihydro-narbonolide + 10-deoxymethynolide + CoA + CO2 + NADP+ + H2O
N-(2-[[(2R,3S,4S,6R,8E,10R,11R)-11-hydroxy-2,4,6,10-tetramethyl-3-[[(2-nitrophenyl)methoxy]methoxy]-7-oxotridec-8-en-1-yl]sulfanyl]ethyl)acetamide + methylmalonyl N-acetylcysteamine
?
-
-
-
-
?
(3R,4R,5E,8R,10S,11S,12R)-3-hydroxy-4,8,10,12-tetramethyl-11-[[(2-nitrophenyl)methoxy]methoxy]-13-(phenylsulfanyl)tridec-5-en-7-one + methylmalonyl N-acetylcysteamine
?
-
-
-
-
?
(3R,4R,5E,8R,10S,11S,12R)-3-hydroxy-4,8,10,12-tetramethyl-11-[[(2-nitrophenyl)methoxy]methoxy]-13-(phenylsulfanyl)tridec-5-en-7-one + methylmalonyl N-acetylcysteamine
?
-
-
-
-
?
(E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate + (2S)-methylmalonyl-CoA + NADPH + H+
narbonolide + ?
the engineered polyketide synthase PikAIII-TE(thioesterase domain) fusion protein accepts and processes the pentaketide to produce 10-deoxymethynolide as the sole product. The polyketide synthase PikAIII/polyketide synthase PikAIV complex processes the pentaketide to produce 10-deoxymethynolide and narbonolide. After incubation of the hexaketide with polyketide synthase PikAIII-TE(thioesterase domain) fusion protein in both the presence and absence of NADPH, no product formation is observed
-
-
?
(E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate + (2S)-methylmalonyl-CoA + NADPH + H+
narbonolide + ?
the engineered polyketide synthase PikAIII-TE(thioesterase domain) fusion protein accepts and processes the pentaketide to produce 10-deoxymethynolide as the sole product. The polyketide synthase PikAIII/polyketide synthase PikAIV complex processes the pentaketide to produce 10-deoxymethynolide and narbonolide. After incubation of the hexaketide with polyketide synthase PikAIII-TE(thioesterase domain) fusion protein in both the presence and absence of NADPH, no product formation is observed
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-
?
hexaketide N-acetyl cysteamine thioester + (2S)-methylmalonyl-CoA + NADPH + H+
narbonolide + ?
incubation of the monomodular polyketide synthase PikAIV with hexaketide and 2-methylmalonyl-CoA results in chain extension to the final heptaketide, release, and cyclization to afford narbonolide. The polyketide synthase PikAIII/polyketide synthase PikAIV complex processes the pentaketide to produce 10-deoxymethynolide and narbonolide. No activity with (E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate (i.e. pentaketide) to produce 10-deoxymethynolide
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-
?
hexaketide N-acetyl cysteamine thioester + (2S)-methylmalonyl-CoA + NADPH + H+
narbonolide + ?
incubation of the monomodular polyketide synthase PikAIV with hexaketide and 2-methylmalonyl-CoA results in chain extension to the final heptaketide, release, and cyclization to afford narbonolide. The polyketide synthase PikAIII/polyketide synthase PikAIV complex processes the pentaketide to produce 10-deoxymethynolide and narbonolide. No activity with (E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate (i.e. pentaketide) to produce 10-deoxymethynolide
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-
?
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
the product narbonolide is an intermediate in the biosynthesis of methymycin
-
-
?
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
the enzyme also produces 10-deoxymethynolide (see EC 2.3.1.239, 10-deoxymethynolide synthase). The enzyme has 29 active sites arranged in four polypeptides (pikAI - pikAIV) with a loading domain, six extension modules and a terminal thioesterase domain. Each extension module contains a ketosynthase (KS), keto reductase (KR), an acyltransferase (AT) and an acyl-carrier protein (ACP). Not all active sites are used in the biosynthesis
-
-
?
methylmalonyl-N-acetylcysteamine + S-phenyl (2S,4R,6E,8R,9R)-9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
3-dihydro-narbonolide + 10-deoxymethynolide + CoA + CO2 + NADP+ + H2O
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products formed by chimeric polykeitde synthase construcuts
-
?
methylmalonyl-N-acetylcysteamine + S-phenyl (2S,4R,6E,8R,9R)-9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
3-dihydro-narbonolide + 10-deoxymethynolide + CoA + CO2 + NADP+ + H2O
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products formed by chimeric polykeitde synthase construcuts
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?
additional information
?
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despite clear similarities in biochemistry and underlying module organization the picromycin synthase modules 5+TE(thioesterase) and 6+TE(thioesterase) show clear differences in substrate specificity and tolerance
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?
additional information
?
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by modification of the type of hexaketide ester employed, product formation may be controled with greater than 10:1 selectivity for either full module catalysis, leading to a 14-membered macrolactone, or direct cyclization to a 12-membered ring
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-
?
additional information
?
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by modification of the type of hexaketide ester employed, product formation may be controled with greater than 10:1 selectivity for either full module catalysis, leading to a 14-membered macrolactone, or direct cyclization to a 12-membered ring
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-
?
additional information
?
-
despite clear similarities in biochemistry and underlying module organization the picromycin synthase modules 5+TE(thioesterase) and 6+TE(thioesterase) show clear differences in substrate specificity and tolerance
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?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
enzyme utilizes an oxidized quinone as co-factor
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additional information
-
enzyme utilizes an oxidized quinone as co-factor
-
additional information
-
enzyme utilizes an oxidized quinone as cofactor
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.41
(E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
pH 7.2, 30°C, Km-valkue for activity with the polyketide synthase PikAIII/polyketide synthase PikAIV complex in formation of narbonolide
additional information
additional information
both PikAIV(DELTAAT) and PikAIV(DELTAACP) display similar apparent kcat values for 10-deoxymethynolide production, which are approximately 2fold lower than the calculated kcat from wild-type PikAIII and PikAIV. Likewise, both PikAIV mutants display similar apparent KM values that are also reduced 2fold when compared to the KM from PikAIII and PikAIV. The equivalent decrease in the apparent kinetic parameters for both mutants results in a specificity constant (kcat/KM) that is comparable to wild-type, further emphasizing the non-critical role of these catalytic domains in 10-deoxymethynolide production. Both PikAIII(DELTADock) (partial deletions of PikAIII C-terminal domain) and PikAIV(DELTADock) (partial deletion of PikAIV N-terminal docking domains) display apparent kcat values (0.044/min and 0.053/min), which are significantly decrease relative to the kcat observed with wild-type PikAIII and PikAIV. The apparent KM values for PikAIII(DELTADock) and PikAIV (DELTADock) decrease 35 fold compared to wild-type, resulting in specificity constants (kcat/KM) that are 14fold and 8fold lower, respectively. Combining PikAIII(DELTADock) and PikAIV(DELTADock) together do not result in an additional rate decrease. The kinetic parameters are comparable to those obtained when either truncated monomodule is paired with its wild-type partner
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.055
(E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
pH 7.2, 30°C, kcat for activity with the polyketide synthase PikAIII/polyketide synthase PikAIV complex in formation of narbonolide
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.13
(E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
pH 7.2, 30°C, kcat/Km-value for activity with the polyketide synthase PikAIII/polyketide synthase PikAIV complex in formation of narbonolide
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Q9ZGI5: type I polyketide synthase PikAI, Q9ZGI4: type I polyketide synthase PikAII, Q9ZGI3: type I polyketide synthase PikAIII, Q9ZGI2: type I polyketide synthase PikAIV, Q9ZGI1: thioesterase II PikAV
SwissProt
brenda
Q9ZGI5: type I polyketide synthase PikAI, Q9ZGI4: type I polyketide synthase PikAII, Q9ZGI3: type I polyketide synthase PikAIII, Q9ZGI2: type I polyketide synthase PikAIV, Q9ZGI1: thioesterase II PikAV. Multifunctional, modular enzyme
SwissProt
brenda
Q9ZGI5: type I polyketide synthase PikAI, Q9ZGI4: type I polyketide synthase PikAII, Q9ZGI3: type I polyketide synthase PikAIII, Q9ZGI2: type I polyketide synthase PikAIV, Q9ZGI1: thioesterase II PikAV. Multifunctional, modular enzyme
SwissProt
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
the enzyme is involved in the biosynthesis of narbonomycin
physiological function
-
in modular type I polyketide synthases the presence of the three processing domains, i.e. ketoreductase (KR), dehydratase (DH), and enoylreductase (ER), are varied in each module, leading to a fully reduced, partially reduced, or unreduced segment on the polyketide chain. Dehydratase PikDH2 converts D-alcohol substrates to trans-olefin products. The reaction is reversible with equilibrium constants ranging from 1.2 to 2. The enzyme activity is robust, and PikDH2 can be used for the chemoenzymatic synthesis of unsaturated triketide products. PikDH2 shows remarkably strict substrate specificity and is unable to turn over substrates that are epimeric at the beta-, gamma-, or delta-position
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
pikromyin polyketide synthase is comprised of a loading module and six extension modules. PikAI is a multimodular component of this pikromyin polyketide synthase and houses both the loading domain and the first two extension modules, joined by short intraprotein linkers
additional information
the enzyme is a multifunctional, modular polyketide synthase
additional information
-
pikromyin polyketide synthase is comprised of a loading module and six extension modules. PikAI is a multimodular component of this pikromyin polyketide synthase and houses both the loading domain and the first two extension modules, joined by short intraprotein linkers
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additional information
-
the enzyme is a multifunctional, modular polyketide synthase
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
multimodular separation can lead to only a modest decrease in the overall production of the final polyketide production. PikAI is a multimodular component of the pikromyin polyketide synthase and houses both the loading domain and the first two extension modules, joined by short intraprotein linkers. PikAI can be separated into two proteins at either of these linkers, only when matched pairs of docking domains from a heterologous modular phoslactomycin PKS are used in place of the intraprotein linker. In both cases the yields of pikromycin produced by the Streptomyces venezuelae mutant are 50% of that of a Streptomyces venezuelae strain expressing the native trimodular PikAI. Expression of module 2 as a monomodular protein fused to a heterologous N-terminal docking domain is also observed to give almost a tenfold improvement in the in vivo generation of pikromycin from a synthetic diketide intermediate
additional information
PikAI is a multimodular component of the pikromyin polyketide synthase and houses both the loading domain and the first two extension modules, joined by short intraprotein linkers. PikAI can be separated into two proteins at either of these linkers, only when matched pairs of docking domains from a heterologous modular phoslactomycin polyketide synthase are used in place of the intraprotein linker. In both cases the yields of pikromycin produced by the Streptomyces venezuelae mutant are 50% of that of a Streptomyces venezuelae strain expressing the native trimodular PikAI. This observation provides evidence that such separations do not dramatically impact the efficiency of the entire in vivo biosynthetic process. Expression of module 2 as a monomodular protein fused to a heterologous N-terminal docking domain is also observed to give almost a tenfold improvement in the in vivo generation of pikromycin from a synthetic diketide intermediate. These results demonstrate the utility of docking domains to manipulate biosynthetic processes catalyzed by modular polyketide synthases and the quest to generate novel polyketide products
additional information
-
multimodular separation can lead to only a modest decrease in the overall production of the final polyketide production. PikAI is a multimodular component of the pikromyin polyketide synthase and houses both the loading domain and the first two extension modules, joined by short intraprotein linkers. PikAI can be separated into two proteins at either of these linkers, only when matched pairs of docking domains from a heterologous modular phoslactomycin PKS are used in place of the intraprotein linker. In both cases the yields of pikromycin produced by the Streptomyces venezuelae mutant are 50% of that of a Streptomyces venezuelae strain expressing the native trimodular PikAI. Expression of module 2 as a monomodular protein fused to a heterologous N-terminal docking domain is also observed to give almost a tenfold improvement in the in vivo generation of pikromycin from a synthetic diketide intermediate
-
additional information
-
PikAI is a multimodular component of the pikromyin polyketide synthase and houses both the loading domain and the first two extension modules, joined by short intraprotein linkers. PikAI can be separated into two proteins at either of these linkers, only when matched pairs of docking domains from a heterologous modular phoslactomycin polyketide synthase are used in place of the intraprotein linker. In both cases the yields of pikromycin produced by the Streptomyces venezuelae mutant are 50% of that of a Streptomyces venezuelae strain expressing the native trimodular PikAI. This observation provides evidence that such separations do not dramatically impact the efficiency of the entire in vivo biosynthetic process. Expression of module 2 as a monomodular protein fused to a heterologous N-terminal docking domain is also observed to give almost a tenfold improvement in the in vivo generation of pikromycin from a synthetic diketide intermediate. These results demonstrate the utility of docking domains to manipulate biosynthetic processes catalyzed by modular polyketide synthases and the quest to generate novel polyketide products
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression of functional polyketide synthase modules in Escherichia coli
overexpression of pikromycin modules PikAIII and PIkAIV in Escherichia coli
overexpression of polyketide synthase PikAIII, and polyketide synthase PikAIV in Escherichia coli
the picromycin/methymycin PKS genes (pikAI, PikAII, PikAIII, PikAIV and pikAV) are functionally expressed in the heterologous host Streptomyces lividans, resulting in production of both narbonolide and 10-deoxymethynolide
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
synthesis
-
substrate engineering approaches to control the catalytic cycle of a full polykeitde synthase module harboring multiple domains. Using alternatively activated native hexaketide substrates, product formation may be controled with greater than 10:1 selectivity for either full module catalysis, leading to a 14-membered macrolactone, or direct cyclization to a 12-membered ring
synthesis
-
versatile method for generating and identifying functional chimeric PKS enzymes for synthesizing custom macrolactones and macrolides. PKS genes from the pikromycin and erythromycin pathways are hybridized in Saccharomyces cerevisiae to generate hybrid libraries. Streptomyces venezuelae strains that expressed active chimeric enzymes with new functionality are capable of producing engineered macrolactones
synthesis
-
versatile method for generating and identifying functional chimeric PKS enzymes for synthesizing custom macrolactones and macrolides. PKS genes from the pikromycin and erythromycin pathways are hybridized in Saccharomyces cerevisiae to generate hybrid libraries. Streptomyces venezuelae strains that expressed active chimeric enzymes with new functionality are capable of producing engineered macrolactones
-
synthesis
-
substrate engineering approaches to control the catalytic cycle of a full polykeitde synthase module harboring multiple domains. Using alternatively activated native hexaketide substrates, product formation may be controled with greater than 10:1 selectivity for either full module catalysis, leading to a 14-membered macrolactone, or direct cyclization to a 12-membered ring
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lu, H.; Tsai, S.; Khosla, C.; Cane, D.
Expression, site-directed mutagenesis, and steady state kinetic analysis of the terminal thioesterase domain of the methymycin/picromycin polyketide synthase
Biochemistry
41
12590-12597
2002
Streptomyces venezuelae (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1)
brenda
Kittendorf, J.D.; Beck, B.J.; Buchholz, T.J.; Seufert, W.; Sherman, D.H.
Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase
Chem. Biol.
14
944-954
2007
Streptomyces venezuelae (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1)
brenda
Tang, L.; Fu, H.; Betlach, M.C.; McDaniel, R.
Elucidating the mechanism of chain termination switching in the picromycin/methymycin polyketide synthase
Chem. Biol.
6
553-558
1999
Streptomyces venezuelae (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1)
brenda
Yan, J.; Gupta, S.; Sherman, D.H.; Reynolds, K.A.
Functional dissection of a multimodular polypeptide of the pikromycin polyketide synthase into monomodules by using a matched pair of heterologous docking domains
ChemBioChem
10
1537-1543
2009
Streptomyces venezuelae (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1), Streptomyces venezuelae ATCC 15439 (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1)
brenda
Yin, Y.; Lu, H.; Khosla, C.; Cane, D.E.
Expression and kinetic analysis of the substrate specificity of modules 5 and 6 of the picromycin/methymycin polyketide synthase
J. Am. Chem. Soc.
125
5671-5676
2003
Streptomyces venezuelae (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1), Streptomyces venezuelae ATCC 15439 (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1)
brenda
Aldrich, C.C.; Beck, B.J.; Fecik, R.A.; Sherman, D.H.
Biochemical investigation of pikromycin biosynthesis employing native penta- and hexaketide chain elongation intermediates
J. Am. Chem. Soc.
127
8441-8452
2005
Streptomyces venezuelae (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1), Streptomyces venezuelae ATCC 15439 (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1)
brenda
Whicher, J.R.; Dutta, S.; Hansen, D.A.; Hale, W.A.; Chemler, J.A.; Dosey, A.M.; Narayan, A.R.; Hakansson, K.; Sherman, D.H.; Smith, J.L.; Skiniotis, G.
Structural rearrangements of a polyketide synthase module during its catalytic cycle
Nature
510
560-564
2014
Streptomyces venezuelae (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1), Streptomyces venezuelae ATCC 15439 (Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1)
brenda
Chemler, J.A.; Tripathi, A.; Hansen, D.A.; ONeil-Johnson, M.; Williams, R.B.; Starks, C.; Park, S.R.; Sherman, D.H.
Evolution of efficient modular polyketide synthases by homologous recombination
J. Am. Chem. Soc.
137
10603-10609
2015
Streptomyces venezuelae, Streptomyces venezuelae ATCC 15439
brenda
Hansen, D.A.; Koch, A.A.; Sherman, D.H.
Substrate controlled divergence in polyketide synthase catalysis
J. Am. Chem. Soc.
137
3735-3738
2015
Streptomyces venezuelae, Streptomyces venezuelae ATCC 15439
brenda
Li, Y.; Dodge, G.J.; Fiers, W.D.; Fecik, R.A.; Smith, J.L.; Aldrich, C.C.
Functional characterization of a dehydratase domain from the pikromycin polyketide synthase
J. Am. Chem. Soc.
137
7003-7006
2015
Streptomyces venezuelae
brenda
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