Effect of Post–Polyketide Synthase Modification Groups on Property and Activity of Polyene Macrolides

The biosynthesis of polyene macrolides, which are natural products produced by soil actinomycetes, have been extensively explored, and recent studies have focused on the effects of post–polyketide synthase (PKS) modifications to polyene macrolides on toxicity, water solubility, and antifungal activity. For example, there are interactions between glycosyl, carboxyl, and hydroxyl or epoxy groups generated in the post-PKS modification steps; salt bridges will be formed between carboxylate and ammonium on the mycosamine; and water bridges will be formed between hydroxy and hydroxyl on mycosamine. These interactions will affect their water solubility and substrate-recognition specificity. This review summarizes research related to these post-PKS modification groups and discusses some genetic engineering operation problems and solutions that may be encountered when modifying these post-PKS modification groups. In addition, this review provides a basis for the structural research of polyene macrolide antibiotics and contributes to comprehensive and systematic knowledge, and it may thus encourage researchers to develop novel antifungal drugs with higher therapeutic indexes and medical values.