Analysis of the Indanomycin Biosynthetic Gene Cluster from Streptomyces antibioticus NRRL 8167

Metabolites that harbor a core indane scaffold are found to have diverse biological properties. Indanomycin and related pyrroloketoindanes are ionophores and have demonstrated antiparasitic, insecticidal, and antibacterial activities. To understand the biochemical mechanism guiding formation of the central indaneuring, the biosynthetic gene cluster for indanomycin was identified from Streptomyces antibioticus NRRL 8167 and sequenced to similar to 80 kb; this revealed five genes encoding subunits of a polyketide synthase (PKS) and 18 other open reading frames. The involvement of this cluster in indanomycin biosynthesis was confirmed by deletion mutagenesis. The indanomycin PKS lacks the expected thioesterase at the carboxy terminus of the final module, and instead appears to house an incomplete module containing an unusual cyclase domain. These findings now enable additional detailed genetic and biochemicals studies of the mechanism guiding the generation of pyrroloketoindanes.