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Literature summary for 1.13.12.17 extracted from

  • Howard-Jones, A.R.; Walsh, C.T.
    Staurosporine and rebeccamycin aglycones are assembled by the oxidative action of StaP, StaC, and RebC on chromopyrrolic acid (2006), J. Am. Chem. Soc., 128, 12289-12298.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
additional information StaP, a cytochrome P450 enzyme, catalyzes an aryl-aryl bond-forming reaction to give a six-ring indolocarbazole scaffold, as well as mediating decarboxylation and oxidation of the putative dicarboxypyrrole moiety. This action requires two to four cycles of net two-electron substrate oxidation at the catalytic heme center. StaP produces three distinct products, differing in oxidation level. For the production of K252c from chromopyrrolic acid, a net four-electron oxidation is required. The generation ofarcyriaflavin A from chromopyrrolic acid requires an overall eight-electron oxidation. StaP is thus unusual in the apparent lack of oxidative control it possesses over the outcome of its catalytic turnover. Control of the overall oxidation route is provided by a second enzyme StaC, which imparts the net effect of directing the oxidation level of the pyrrole-derived ring. While StaP in isolation gives three aglycone forms, StaP and StaC turn over chromopyrrolic acid to give only a single product, K252c. Similarly, RebC guides the turnover of chromopyrrolic acid toward the more highly oxidized maleimide-bearing aglycone, arcyriaflavin A Streptomyces longisporoflavus

Cloned(Commentary)

Cloned (Comment) Organism
expression of StaP, StaC, and RebC in Escherichia coli Streptomyces longisporoflavus

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
48000
-
x * 48000, SDS-PAGE Streptomyces longisporoflavus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
dichlorochromopyrrolate + 4 O2 + 4 NADH + 4 H+ Streptomyces longisporoflavus the reaction is catalyzed by enzyme StaP. StaC and RebC acting to direct the level of oxidation in the newly formed five-membered ring. Biosynthesis of the antitumor indolocarbazoles rebeccamycin and staurosporine by streptomycetes 1,11-dichloroarcyriaflavin A + 2 CO2 + 6 H2O + 4 NAD+
-
?

Organism

Organism UniProt Comment Textmining
Streptomyces longisporoflavus Q06IS2
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Streptomyces longisporoflavus

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
dichlorochromopyrrolate + 4 O2 + 4 NADH + 4 H+ the reaction is catalyzed by enzyme StaP. StaC and RebC acting to direct the level of oxidation in the newly formed five-membered ring. Biosynthesis of the antitumor indolocarbazoles rebeccamycin and staurosporine by streptomycetes Streptomyces longisporoflavus 1,11-dichloroarcyriaflavin A + 2 CO2 + 6 H2O + 4 NAD+
-
?
dichlorochromopyrrolate + 4 O2 + 4 NADH + 4 H+ StaP, a cytochrome P450 enzyme, catalyzes an aryl-aryl bond-forming reaction to give a six-ring indolocarbazole scaffold, as well as mediating decarboxylation and oxidation of the putative dicarboxypyrrole moiety. This action requires two to four cycles of net two-electron substrate oxidation at the catalytic heme center. StaP produces three distinct products, differing in oxidation level. For the production of K252c from chromopyrrolic acid, a net four-electron oxidation is required. The generation ofarcyriaflavin A from chromopyrrolic acid requires an overall eight-electron oxidation. StaP is thus unusual in the apparent lack of oxidative control it possesses over the outcome of its catalytic turnover. Control of the overall oxidation route is provided by a second enzyme StaC, which imparts the net effect of directing the oxidation level of the pyrrole-derived ring. While StaP in isolation gives three aglycone forms, StaP and StaC turn over chromopyrrolic acid to give only a single product, K252c. Similarly, RebC (flavin-dependent hydroxylase) guides the turnover of chromopyrrolic acid toward the more highly oxidized maleimide-bearing aglycone, arcyriaflavin A Streptomyces longisporoflavus 1,11-dichloroarcyriaflavin A + 2 CO2 + 6 H2O + 4 NAD+
-
?

Subunits

Subunits Comment Organism
? x * 48000, SDS-PAGE Streptomyces longisporoflavus

Synonyms

Synonyms Comment Organism
StaP
-
Streptomyces longisporoflavus

Cofactor

Cofactor Comment Organism Structure
cytochrome P450 StaP is a cytochrome P450 enzyme Streptomyces longisporoflavus
Ferredoxin required for activity Streptomyces longisporoflavus
NADH NADH is the preferred reductant for StaC- and RebC-mediated turnover of FAD required for activity Streptomyces longisporoflavus