+ 4 NADH
+ 4 H+
Dichloroarcyriaflavin A synthase
| Dichloroarcyriaflavin A synthase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 1.13.12.17 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
Dichloroarcyriaflavin A synthase (EC 1.13.12.17) is an enzyme with systematic name dichlorochromopyrrolate,NADH:oxygen 2,5-oxidoreductase (dichloroarcyriaflavin A-forming).[1] This enzyme catalyses the following overall chemical reaction:[2]
The reaction proceeds in two stages. The first protein component, called RebP, is an oxidase which contains heme and uses oxygen and nicotinamide adenine dinucleotide (NADH) to form the new aromatic bond between the indole components, making a six-membered ring.[3] The RebP component then acts with a flavin-dependent partner called RebC to remove the two carboxylic acid groups by oxidative decarboxylation.[4]
The product of the reaction is an indole alkaloid and gives rebeccamycin in a subsequent reaction. The naming of the various proteins involved in its biosynthesis as "RebC" etc describe the overall pathway.[5][6]
References
- ^ Sánchez C, Zhu L, Braña AF, Salas AP, Rohr J, Méndez C, Salas JA (January 2005). "Combinatorial biosynthesis of antitumor indolocarbazole compounds". Proceedings of the National Academy of Sciences of the United States of America. 102 (2): 461–6. doi:10.1073/pnas.0407809102. PMC 544307. PMID 15625109.
- ^ Enzyme 1.13.12.17 at KEGG Pathway Database.
- ^ Makino M, Sugimoto H, Shiro Y, Asamizu S, Onaka H, Nagano S (July 2007). "Crystal structures and catalytic mechanism of cytochrome P450 StaP that produces the indolocarbazole skeleton". Proceedings of the National Academy of Sciences of the United States of America. 104 (28): 11591–6. Bibcode:2007PNAS..10411591M. doi:10.1073/pnas.0702946104. PMC 1913897. PMID 17606921.
- ^ Howard-Jones AR, Walsh CT (September 2006). "Staurosporine and rebeccamycin aglycones are assembled by the oxidative action of StaP, StaC, and RebC on chromopyrrolic acid". Journal of the American Chemical Society. 128 (37): 12289–98. Bibcode:2006JAChS.12812289H. doi:10.1021/ja063898m. PMID 16967980.
- ^ Howard-Jones AR, Walsh CT (December 2005). "Enzymatic genеration of the chromopyrrolic acid scaffold of rebeccamycin by the tandem action of RebO and RebD". Biochemistry. 44 (48): 15652–63. CiteSeerX 10.1.1.537.5773. doi:10.1021/bi051706e. PMID 16313168.
- ^ Pommerehne, Kathrin; Walisko, Jana; Ebersbach, Anna; Krull, Rainer (2019). "The antitumor antibiotic rebeccamycin—challenges and advanced approaches in production processes". Applied Microbiology and Biotechnology. 103 (9): 3627–3636. doi:10.1007/s00253-019-09741-y. PMID 30888461.
External links
- Dichloroarcyriaflavin+A+synthase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)