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

隐蔽mdk基因簇的异源表达和maduralactomycin A的结构修订

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作者:Jan W Schwitalla, Ngoc-Thao-Hien Le, Soohyun Um, Felix Schalk, Mark Brönstrup, Martin Baunach, Christine Beemelmanns

Abstract

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.

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