Add sugar…︁ Cloning and heterologous expression of the aranciamycin biosynthetic gene cluster revealed a new flexible glycosyltransferase, AraGT, which accepts different nucleotide‐activated sugars (D‐amicetose, L‐rhodinose, L‐rhamnose and L‐axenose) The newly generated aranciamycin derivatives displayed antiproliferative activity against MaTu and MCF7 cells; this shows that the deoxysugar is important for anticancer activity.

The formation of landomycin A or one of its derivatives (5,6-anhydrolandomycin A) in a heterologous strain has never been achieved. It has now been made possible by the coexpression of a cosmid containing all biosynthetic genes necessary to produce landomycin A together with a pathway-specific regulatory gene. As host we used a polyketide synthase-defective mutant strain of Streptomyces fradiae Tu «2717 which is not able to produce urdamycin A. Our results indicate that four glycosyltransferases are responsible for the formation of the hexasaccharide side chain of landomycin A.

LanV is involved in the biosynthesis of landomycin A. The exact function of this enzyme was elucidated with combinatorial biosynthesis by using Streptomyces fradiae mutants that produce urdamycin A. After expression of lanV in S. fradiae DeltaurdM, which is a mutant that accumulates rabelomycin, urdamycinon B and urdamycin B were found to be produced by the strain. This result indicates that LanV is involved in the 6-ketoreduction of the angucycline core, which preceeds a 5,6-dehydration reaction. 9-C-D-Olivosyltetrangulol was also produced by this strain; this demonstrates that LanV catalyses the aromatization of ring A of the angucycline structure. Coexpression of lanV and lanGT2 in S. fradiae AO, a mutant that lacks all four urdamycin glycosyltransferases, resulted in the production of tetrangulol and the glycoside landomycin H, both of which have an aromatic ring A. As glycosylated angucyclines were not observed after expression of lanGT2 in the absence of lanV, we conclude that LanGT2 needs an aromatized ring A for substrate recognition.

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