posted on 2025-03-24, 16:05authored byDoudou Dong, Wei Zhang, Wei Ding
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.