Staurosporine and rebeccamycin are natural antitumor compounds produced by actinomycetes. Indolocarbazole biosynthetic gene clusters have been cloned from both Streptomyces sp. TP-A0274 and Lechevalieria aerocolonigenes ATCC39243. Staurosporine biosynthetic gene cluster consists of 15 orfs spanning 22 kb, and rebeccamycin biosynthetic gene cluster consists of 10 orfs spanning 16 kb. Gene disruption and bioconversion experiments revealed that indole-3-pyruvic acid, which is derived from tryptophan, is coupled to yield chromopyrrolic acid, and then this dicarboxylic bisindole compound is transformed into the indolocarbazole skeleton via two oxidation steps. Goadsporin is another heterocyclic antibiotic produced by Streptomyces sp. TP-A0584. It is a polypeptide antibiotic containing the thiazole and oxazole rings. The biosynthetic goadsporin gene cluster consists of 10 genes: a structural gene godA and nine genes involved in post-translational modification, immunity, and transcriptional regulation. It is particularly noteworthy that godI, which shows high similarity to the subunit of the “signal recognition particle,” plays an important role in goadsporin immunity. Furthermore, combinatorial biosynthesis was applied to produce the indolocarbazole and goadsporin analogs, and as a result, 14 analogs of indolocarbazole and 4 of goadsporin were produced.