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.