MoeH 5: a natural glycorandomizer from the moenomycin biosynthetic pathway

Summary The biosynthesis of the phosphoglycolipid antibiotic moenomycin A attracts the attention of researchers hoping to develop new moenomycin‐based antibiotics against multidrug resistant G ram‐positive infections. There is detailed understanding of most steps of this biosynthetic pathway in S treptomyces ghanaensis ( ATCC 14672), except for the ultimate stage, where a single pentasaccharide intermediate is converted into a set of unusually modified final products. Here we report that only one gene, moeH5 , encoding a homologue of the glutamine amidotransferase ( GAT ) enzyme superfamily, is responsible for the observed diversity of terminally decorated moenomycins. Genetic and biochemical evidence support the idea that MoeH 5 is a novel member of the GAT superfamily, whose homologues are involved in the synthesis of various secondary metabolites as well as K and O antigens of bacterial lipopolysaccharide. Our results provide insights into the mechanism of MoeH 5 and its counterparts, and give us a new tool for the diversification of phosphoglycolipid antibiotics.