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NDP-4-keto-6-deoxyglucose-3-dehydratase KsgR in complex with PMP and AKG
Structural highlights
FunctionPublication Abstract from PubMedKasugamine (2,4-diamino-2,3,4,6-tetradeoxy-d-mannose, 1) is a rare multideoxy diamino-sugar forming the core skeleton of the commercial aminoglycoside antibiotic Kasugamycin (KSG, 2), an agricultural fungicide that has been used against rice blast disease for more than 60 years. Despite the reported biosynthetic gene cluster (BGC) for 2, the enzymatic logic leading to the formation of 1 remained unclear. Here, we report the biosynthetic mechanism of 1. Five enzymes horizontal line KsgQ, KsgB, KsgD, KsgR, and KsgC horizontal line can biochemically convert uridine diphosphate-N-acetyl-d-glucosamine (UDP-GlcNAc, 4) to generate the sugar donor 6, which is incorporated into 2, as confirmed by stable isotope-labeled feeding experiments. KsgB is characterized as the first enzyme catalyzing the deacetylation of uridine diphosphate-N-acetyl-d-mannosamine (UDP-ManNAc, 5), while KsgR represents the first UDP-sugar 3-dehydrase catalyzing the C-3 deoxygenation of the KsgD product (8) via the cofactors pyridoxal-5'-phosphate (PLP) and l-glutamic acid (l-Glu), and employs a ColD-like catalytic mechanism, as shown by crystallographic analysis, molecular docking, and site-directed mutagenesis. Our findings unravel the biosynthetic mysteries of 1, highlight the intriguing strategies for biosynthesizing diamino-sugars in nature, and provide some evidence for further completely uncovering the biosynthetic logic of 2. Characterization of UDP-Sugar 3-Dehydrase KsgR in the Biosynthesis of a Distinctive Multideoxy Diamino-Sugar Kasugamine of Kasugamycin.,Li Y, Chen Y, Shi J, Wu J, Wang Y, Ren J, Li Y, Zhou J, Gao Q, Mei K, Guo Z J Am Chem Soc. 2026 May 13;148(18):19205-19213. doi: 10.1021/jacs.6c03331. Epub , 2026 May 3. PMID:42076866[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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