Heterologous expression of the cryptic mdk gene cluster and structural revision of maduralactomycin A

After conducting an in silico analysis of the cryptic mdk cluster region and performing transcriptomic studies, an integrative Streptomyces BAC Vector containing the mdk gene sequence was constructed. The heterologous expression of the mdk cluster in Streptomyces albus J1074 resulted in the production of the angucyclic product, seongomycin, which allowed for the assesment of its antibacterial, antiproliferative, and antiviral activities. Heterologous production was further confirmed by targeted knock-out experiments involving key regulators of the biosynthetic pathways. We were further able to revise the core structure of maduralactomycin A, using a computational approach.

Automated summary

After analyzing the cryptic mdk cluster region and performing transcriptomic studies, a Streptomyces BAC vector containing the mdk gene sequence was constructed and used for heterologous expression in different Streptomyces strains. The expressed mdk cluster produced a novel compound called seongomycin, which exhibited antibacterial, antiproliferative, and antiviral activities. The core structure of maduralactomycin A was also revised using a computational approach.