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.