Rebeccamycin biosynthesis protein RebC (RebC)

RebC is a flavin-dependent monooxygenase essential for the biosynthesis of rebeccamycin, an indolocarbazole natural product with potent anti-tumor properties produced by the actinomycete Lechevalieria aerocolonigenes (UniProt Q8KHV5). It works in tandem with the enzyme RebD to process the intermediate chromopyrrolate, facilitating the oxidative cyclization and decarboxylation required to form the rebeccamycin aglycone (PubMed: 16150558). RebC acts as a regulatory filter in the pathway; in its absence, the pathway produces arcyriaflavin A, whereas its presence directs the synthesis toward the more complex rebeccamycin structure (PubMed: 15702915). By sequestering reactive intermediates, RebC ensures the correct regiochemistry of the final product. Although not a target for therapeutic drugs in the traditional sense, RebC is a vital tool in combinatorial biosynthesis and metabolic engineering for the creation of novel indolocarbazole derivatives with improved pharmacological profiles (PubMed: 16430491). Its structural biology has been extensively studied to understand how flavin-dependent enzymes can control complex chemical rearrangements in secondary metabolism. The enzyme requires FAD as a cofactor and utilizes molecular oxygen to perform its catalytic function. Researchers utilize RebC in synthetic biology to diversify the chemical space of indolocarbazoles, which are known to inhibit DNA topoisomerase I.

Other names

FAD-dependent monooxygenase RebCChromopyrrolate monooxygenaseRebeccamycin synthase CRebeccamycin biosynthesis protein C

Not applicable as RebC is a biosynthetic enzyme rather than a therapeutic drug target.