A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

Unravelling key enzymatic steps in C-ring cleavage during angucycline biosynthesis




TekijätElsayed Somayah S., van der Heul Helga U., Xiao Xiansha, Nuutila Aleksi, Baars Laura R., Wu Changsheng, Metsä-Ketelä Mikko, van Wezel Gilles P.

KustantajaNature Publishing Group

Julkaisuvuosi2023

JournalCommunications chemistry

Tietokannassa oleva lehden nimiCOMMUNICATIONS CHEMISTRY

Artikkelin numero 281

Vuosikerta6

ISSN2399-3669

DOIhttps://doi.org/10.1038/s42004-023-01059-1

Verkko-osoitehttps://doi.org/10.1038/s42004-023-01059-1

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/380587098


Tiivistelmä

Angucyclines are type II polyketide natural products, often characterized by unusual structural rearrangements through B- or C-ring cleavage of their tetracyclic backbone. While the enzymes involved in B-ring cleavage have been extensively studied, little is known of the enzymes leading to C-ring cleavage. Here, we unravel the function of the oxygenases involved in the biosynthesis of lugdunomycin, a highly rearranged C-ring cleaved angucycline derivative. Targeted deletion of the oxygenase genes, in combination with molecular networking and structural elucidation, showed that LugOI is essential for C12 oxidation and maintaining a keto group at C6 that is reduced by LugOII, resulting in a key intermediate towards C-ring cleavage. An epoxide group is then inserted by LugOIII, and stabilized by the novel enzyme LugOV for the subsequent cleavage. Thus, for the first time we describe the oxidative enzymatic steps that form the basis for a wide range of rearranged angucycline natural products.


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