Characterization of Early Enzymes Involved in TDP‐Aminodideoxypentose Biosynthesis en Route to Indolocarbazole AT2433 |
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| Authors: | Dr. Pauline Peltier‐Pain Dr. Shanteri Singh Prof. Jon S. Thorson |
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| Affiliation: | 1. Pharmaceutical Sciences Division, University of Wisconsin–Madison, Madison, WI, USA;2. Glycom A/S, Denmark;3. Center for Pharmaceutical Research and Innovation, Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA |
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| Abstract: | The characterization of TDP‐α‐d ‐glucose dehydrogenase (AtmS8), TDP‐α‐d ‐glucuronic acid decarboxylase (AtmS9), and TDP‐4‐keto‐α‐d ‐xylose 2,3‐dehydratase (AtmS14), involved in Actinomadura melliaura AT2433 aminodideoxypentose biosynthesis, is reported. This study provides the first biochemical evidence that both deoxypentose and deoxyhexose biosynthetic pathways share common strategies for sugar 2,3‐dehydration/reduction and implicates the sugar nucleotide base specificity of AtmS14 as a potential mechanism for sugar nucleotide commitment to secondary metabolism. In addition, a re‐evaluation of the AtmS9 homologue involved in calicheamicin aminodeoxypentose biosynthesis (CalS9) reveals that CalS9 catalyzes UDP‐4‐keto‐α‐d ‐xylose as the predominant product, rather than UDP‐α‐d ‐xylose as previously reported. Cumulatively, this work provides additional fundamental insights regarding the biosynthesis of novel pentoses attached to complex bacterial secondary metabolites. |
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| Keywords: | decarboxylases dehydratases dehydrogenases natural products sugar nucleotides |
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