Chemistry and Biology of Landomycins, an Expanding Family of Polyketide Natural Products

This review covers existing literature (from 1990 to 2008) on landomycins (LS), a family of glycosylated angucyclines, with an emphasis on the bioactivity scope of landomycin (La)-like structures accessible via biocombinatorial manipulations. Some LS display strong antitumor activity and have inspired several chemical studies focused mainly on their unusual deoxysugar chains. A decade of genetic studies on La-producing bacteria has provided many novel molecules with altered structure and activity. A complex nonlinear correlation between the length of the carbohydrate tail of LS and their antitumor activity has also been revealed. It implies that simpler LS than the largest member of the family, LaA, are still potential drug leads. Combinatorial biosynthesis appears to be a powerful tool to search the chemical space around the La scaffold.