A1 Refereed original research article in a scientific journal

The Rieske Oxygenase SnoT Catalyzes 2''-Hydroxylation of L-Rhodosamine in Nogalamycin Biosynthesis




AuthorsNji Wandi Benjamin, Siitonen Vilja, Palmu Kaisa, Metsä-Ketelä Mikko

PublisherWiley - V C H Verlag GmbH & Co. KGaA

Publication year2020

JournalChemBioChem

Volume21

Issue21

First page 3062

Last page3066

Number of pages6

ISSN1439-4227

eISSN1439-7633

DOIhttps://doi.org/10.1002/cbic.202000229(external)

Web address https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202000229(external)

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/47698497(external)


Abstract

Nogalamycin is an anthracycline anti-cancer agent that intercalates into the DNA double helix. The binding is facilitated by two carbohydrate units, L-nogalose and L-nogalamine, that interact with the minor and major grooves of DNA, respectively. However, recent investigations have shown that nogalamycin biosynthesis proceeds through the attachment of l-rhodosamine (2′′-deoxy-4′′-epi-L-nogalamine) to the aglycone. Herein, we demonstrate that the Rieske enzyme SnoT catalyzes 2′′-hydroxylation of L-rhodosamine as an initial post-glycosylation step. Furthermore, we establish that the reaction order continues with 2–5′′ carbocyclization and 4′′ epimerization by the non-heme iron and 2-oxoglutarate-dependent enzymes SnoK and SnoN, respectively. These late-stage tailoring steps are important for the bioactivity of nogalamycin due to involvement of the 2′′- and 4′′-hydroxy groups of ᴸ-nogalamine in hydrogen bonding interactions with DNA.


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