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The Rieske Oxygenase SnoT Catalyzes 2′′‐Hydroxylation of l ‐Rhodosamine in Nogalamycin Biosynthesis
Author(s) -
Nji Wandi Benjamin,
Siitonen Vilja,
Palmu Kaisa,
MetsäKetelä Mikko
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000229
Subject(s) - hydroxylation , chemistry , biosynthesis , stereochemistry , aglycone , biochemistry , dna , enzyme , glycosylation , epimer , glycoside
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.