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

The Rieske Oxygenase SnoT Catalyzes 2''-Hydroxylation of l-Rhodosamine in Nogalamycin Biosynthesis. Chembiochem. 2020 Jun 17;: Authors: Wandi BN, Siitonen V, Palmu K, Metsä-Ketelä M 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, which interact with the minor and major grooves of DNA, respectively. However, recent investigations have shown that nogalamycin biosynthesis proceeds through attachment of l-rhodosamine (2¢¢-deoxy-4¢¢-epi-l-nogalamine) to the aglycone. Here 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¢¢-hydroxyl groups of l-nogalamine in hydrogen bonding interactions with DNA. PMID: 32557994 [PubMed - as supplied by publisher]
Source: Chembiochem - Category: Biochemistry Authors: Tags: Chembiochem Source Type: research