Dichloromethyl-Containing Derivatives from Streptomyces agglomeratus 5-2-6, a Soil Bacterium Isolated from the Qinghai–Tibet Plateau

Six novel dichloromethyl-containing polyketides (1-6), including four pyranone analogs (1-4) and two furanone isomers (5, 6), were isolated from Streptomyces agglomeratus 5-2-6, which was obtained from the Qinghai-Tibet Plateau, China. Additionally, two new linear dichloromethyl compounds (7, 8) were obtained via heterologous expression of agg(A-K) in Streptomyces coelicolor M1152. The structures and absolute configurations of these compounds were primarily elucidated via high-resolution ESIMS, NMR, Mo2(OAc)4-induced electronic circular dichroism, and application of the modified Mosher's method. Notably, 1-6 feature a dichloromethyl moiety, which is reported for the first time in pyranone- and furanone-type natural products. Furthermore, the results of in vivo gene deletion, isotope labeling, and in vitro enzyme reaction experiments revealed a rare single-component flavin-dependent halogenase, AggA, which catalyzes the dichlorination of activated sp3-methylene groups.