Figure 1. Model of bacterial IST biosynthesis.

The biosynthetic scheme shows selected members of the xiamycin family of IST, their biogenetic relationship and their proposed biosynthetic pathway. IST biosynthesis comprises various levels of terpenoid diversification. An epoxidized linear IST-precursor has been proposed to be cyclized to yield preindosespene (1)²¹,²²,²⁶, which is subsequently oxygenated to the carboxylic acid indosespene (2)²²,⁴⁶. 2 has been proposed to be further cyclized into the spiro compound sespenine (4) or the carbazole ring system of xiamycin (3)²¹,²²,²⁶, of which the latter has been proposed to be further diversified to yield the cycloether oxiamycin (5)¹⁸,²³, various N,C- and N,N-fused xiamycin dimers (such as 6a/6b)¹⁸,²²,²³, and sulfonyl-bridged xiamycin dimers (such as 7)¹⁹. Genes encoding enzymes that are involved in the core biosynthesis of the IST scaffold of preindosespene (1) are coloured in blue (xiaEKLM), genes for enzymes that tailor basic scaffolds to more complex ISTs are coloured in red (xiaFGHIJ) and genes with no proposed function are coloured in grey (xiaG). Atoms, bonds or functional groups that are added/are newly formed in biosynthetic reactions are highlighted in the same colour as the gene(s) encoding the gene product(s) that have been proposed to mediate these reactions¹⁸,¹⁹,²²,²⁶,⁴⁶. The length of the scale bar represents a kilobase.