Unraveling the iterative type I polyketide synthases hidden in Streptomyces

Significance Numerous iterative type I polyketide synthases (iT1PKSs) have been discovered in fungi that can synthesize structurally diverse bioactive molecules. However, very few iT1PKSs have been discovered in bacteria. In this work, by combining extensive phylogenetic analysis and experimental verification, we discovered many iT1PKSs inStreptomyces (a bacteria genus), some of which were experimentally confirmed to produce various branched/nonbranched linear intermediates. Particularly, we discovered two bioactive allenic polyketides which are conditionally essential to the producer. In addition, we validated that the phylogenetic analysis is effective in discerning the bacterial iT1PKSs. The widespread existence of iT1PKSs in bacteria is of great significance for both fundamental studies of T1PKS evolution and practical discovery of novel polyketide natural products.