Discovery of Efrotomycin Congeners and Heterologous Expression-Based Insights into the Self-Resistance Mechanism

Four new efrotomycins, A1-A4 (1-4), were isolated from the salt mine-derived Amycolatopsis cihanbeyliensis DSM 45679 and structurally determined. Efrotomycins A3 (3) and A4 (4) feature a tetrahydrofuran ring configured distinctly from known elfamycins. Heterologous expression of the efrotomycin gene cluster (efr BGC) in Streptomyces lividans SBT18 led to efrotomycin B1 (5), the yield of which was improved several fold upon introduction of the transporter gene efrT, a putative self-resistance determinant outside of the efr BGC.