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 mechanisms guiding formation of the central indane ring, the biosynthetic gene cluster for indanomycin was identified from Streptomyces antibioticus NRRL 8167 and sequenced to approximately 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 biochemical studies of the mechanisms guiding the generation of pyrroloketoindanes.

Biosynthetic origins of the ionophore antibiotic indanomycin.

The pyrroloketoindane antibiotic indanomycin is produced by Streptomyces antibioticus NRRL 8167. These hybrid nonribosomal peptide-polyketide ionophore antibiotics are characterized by the presence of an unusual indane ring system, and there is interest in identifying the biochemical mechanisms guiding its biosynthesis. Following incorporation of [1-(13)C]-labeled precursors, the primary metabolic origins of indanomycin were determined to be one unit of L-proline, six units of malonyl-CoA and two units each of methylmalonyl-CoA and ethylmalonyl-CoA.