Biosynthesis indolocarbazole

Sanchez, C., Zhu, L., Brana, A.F. et al. (2005) Combinatorial biosynthesis of antitumor indolocarbazole compounds. Proceedings of the National Academy of Sciences of the United States of America, 102, 461 166. 

Sanchez C, Zhu L, Brana AF, Salas AP, Rohr J, Mendez C, Salas JA (2005) Combinatorial Biosynthesis of Antitumor Indolocarbazole Compounds. Proc Natl Acad Sci USA 102 461... 

Sanchez C, Mendez C, Salas JA (2006) Indolocarbazole natural products occurrence, biosynthesis, and biological activity. Nat Prod Rep 23 1007-1045... 

Salas AP, Zhu L, Sanchez C et al (2005) Deciphering the late steps in the biosynthesis of the anti-tumor indolocarbazole staurosporine sugar donor substrate flexibility of the StaG glycosyltransferase. Mol Microbiol 58 17-27... 

Sanchez C, Salas AP, Brana AF et al (2009) Generation of potent and selective kinase inhibitors by combinatorial biosynthesis of glycosylated indolocarbazoles. Chem Commun 4118 1120... 

The introduction of chlorine into tryptophan at C-7 is proposed as the initial step in the biosynthesis of rebeccamydn (126), the powerful indolocarbazole antitumor antibiotic from Lechevalieria aerocolonigenes [117-119]. The proposed overall biosynthesis of rebeccamydn is shown in Scheme 19.4 [119]. 

Before the identification of the biosynthesis genes involved, different strategies were successful for the production of novel analogs by indolocarbazole-producing microorganisms. Addition of potassium bromide in the fermentation of Lech. 

A gene (ngt) encoding an indolocarbazole N-glycosyltransferase was cloned from the REB producer Lech, aerocolonigenes [21]. Heterologous expression of ngt in either Strep, lividans or Strep, mobaraensis allowed the introduction of a o-glucose moiety into two different indolocarbazoles (Scheme 20.1). These results suggested that ngt was probably involved in REB biosynthesis. 

Studies made with recombinant strains of Strep, alhus showed that formation of the simplest bisindole intermediate during indolocarbazole biosynthesis required the coexpression of two genes rebO and rebD [33]. The said metabolite consisted of chromopyrrolic add (CPA, 37), which seemed to be an intermediate during... 

Fig. 4.40 Intramolecular cross-linking of two indole chrome P450-catalyzed generation of a radical on each of units in the biosynthesis of indolocarbazole alkaloids, the two indole rings, as shown Dimerization is most reasonably explained by the cyto-...

Gao Q, Zhang C, Blanchard S, Thorson JS (2006) Deciphering indolocarbazole and enediyne amino-dideoxypentose biosynthesis through comparative genomics insights from the AT2433 biosynthetic locus. Chem Biol 13 733-743... 

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