Heterologous Expression Leads to Discovery of Diversified Lobophorin Analogues and a Flexible Glycosyltransferase

The heterologous expression of the lobophorin biosynthetic gene cluster from marine-derived Streptomyces pactum SCSIO 02999 has led to the discovery of new analogues that carry d-kijanose (or its variants with a 3-amino or hydroxyl group) at C-9. The identification of intermediates resulting from the inactivation of lobG1 (encoding C-17 kijanosyltransferase) and lobG3 (encoding C-9 digitoxosyltransferase) demonstrates the substrate flexibility of LobG3 to also accept d-kijanose and its variants. Notably, two lobophorins with d-kijanose at C-9 show improved bioactivities.