| EC |
1.13.12.17 |
| Accepted name: |
dichloroarcyriaflavin A synthase |
| Reaction: |
dichlorochromopyrrolate + 4 O2 + 4 NADH + 4 H+ = dichloroarcyriaflavin A + 2 CO2 + 6 H2O + 4 NAD+ |
|
For diagram of rebeccamycin biosynthesis, click here |
| Glossary: |
dichloro-arcyriaflavin A = rebeccamycin aglycone |
| Systematic name: |
dichlorochromopyrrolate,NADH:oxygen 2,5-oxidoreductase (dichloroarcyriaflavin A-forming) |
| Comments: |
The conversion of dichlorochromopyrrolate to dichloroarcyriaflavin A is a complex process that involves two enzyme components. RebP is an NAD-dependent cytochrome P-450 oxygenase that performs an aryl-aryl bond formation yielding the six-ring indolocarbazole scaffold [1]. Along with RebC, a flavin-dependent hydroxylase, it also catalyses the oxidative decarboxylation of both carboxyl groups. The presence of RebC ensures that the only product is the rebeccamycin aglycone dichloroarcyriaflavin A [2]. The enzymes are similar, but not identical, to StaP and StaC, which are involved in the synthesis of staurosporine [3]. |
| Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
| References: |
| 1. |
Makino, M., Sugimoto, H., Shiro, Y., Asamizu, S., Onaka, H. and Nagano, S. Crystal structures and catalytic mechanism of cytochrome P450 StaP that produces the indolocarbazole skeleton. Proc. Natl. Acad. Sci. USA 104 (2007) 11591–11596. [DOI] [PMID: 17606921] |
| 2. |
Howard-Jones, A.R. and Walsh, C.T. Staurosporine and rebeccamycin aglycones are assembled by the oxidative action of StaP, StaC, and RebC on chromopyrrolic acid. J. Am. Chem. Soc. 128 (2006) 12289–12298. [DOI] [PMID: 16967980] |
| 3. |
Sanchez, C., Zhu, L., Brana, A.F., Salas, A.P., Rohr, J., Mendez, C. and Salas, J.A. Combinatorial biosynthesis of antitumor indolocarbazole compounds. Proc. Natl. Acad. Sci. USA 102:461 (2005). [DOI] [PMID: 15625109] |
|
| [EC 1.13.12.17 created 2010] |
| |
|
| |
|
|
EC
|
1.21.3.9
|
| Transferred entry: | dichlorochromopyrrolate synthase, now classified as EC 1.21.98.2, dichlorochromopyrrolate synthase
|
| [EC 1.21.3.9 created 2010 as EC 4.3.1.26, transferred 2013 to EC 1.21.3.9, deleted 2016] |
| |
|
| |
|
| EC |
1.21.98.2 |
| Accepted name: |
dichlorochromopyrrolate synthase |
| Reaction: |
2 3-(7-chloroindol-3-yl)-2-iminopropanoate + H2O2 = dichlorochromopyrrolate + NH3 + 2 H2O |
|
For diagram of rebeccamycin biosynthesis, click here |
| Glossary: |
dichlorochromopyrrolate = 3,4-bis(7-chloro-1H-indol-3-yl)-1H-pyrrole-2,5-dicarboxylate |
| Other name(s): |
RebD; chromopyrrolic acid synthase; chromopyrrolate synthase |
| Systematic name: |
3-(7-chloroindol-3-yl)-2-iminopropanoate ammonia-lyase (dichlorochromopyrrolate-forming) |
| Comments: |
This enzyme catalyses a step in the biosynthesis of rebeccamycin, an indolocarbazole alkaloid produced by the bacterium Lechevalieria aerocolonigenes. The enzyme is a dimeric heme-protein oxidase that catalyses the oxidative dimerization of two L-tryptophan-derived molecules to form dichlorochromopyrrolic acid, the precursor for the fused six-ring indolocarbazole scaffold of rebeccamycin [1]. Contains one molecule of heme b per monomer, as well as non-heme iron that is not part of an iron-sulfur center [2]. In vivo the enzyme uses hydrogen peroxide, formed by the enzyme upstream in the biosynthetic pathway (EC 1.4.3.23, 7-chloro-L-tryptophan oxidase) as the electron acceptor. However, the enzyme is also able to catalyse the reaction using molecular oxygen [3]. |
| Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
| References: |
| 1. |
Nishizawa, T., Gruschow, S., Jayamaha, D.H., Nishizawa-Harada, C. and Sherman, D.H. Enzymatic assembly of the bis-indole core of rebeccamycin. J. Am. Chem. Soc. 128 (2006) 724–725. [DOI] [PMID: 16417354] |
| 2. |
Howard-Jones, A.R. and Walsh, C.T. Enzymatic generation of the chromopyrrolic acid scaffold of rebeccamycin by the tandem action of RebO and RebD. Biochemistry 44 (2005) 15652–15663. [DOI] [PMID: 16313168] |
| 3. |
Spolitak, T. and Ballou, D.P. Evidence for catalytic intermediates involved in generating the chromopyrrolic acid scaffold of rebeccamycin by RebO and RebD. Arch. Biochem. Biophys. 573 (2015) 111–119. [DOI] [PMID: 25837855] |
|
| [EC 1.21.98.2 created 2010 as EC 4.3.1.26, transferred 2013 to EC 1.21.3.9, transferred 2016 to EC 1.21.98.2] |
| |
|
| |
|
|
EC
|
4.3.1.26
|
| Transferred entry: | chromopyrrolate synthase. Now EC 1.21.3.9, dichlorochromopyrrolate synthase
|
| [EC 4.3.1.26 created 2010, deleted 2013] |
| |
|
| |
|
Printable version