Solving the Structural Puzzles of Amipurimycin and Miharamycins Enabled by Stereodivergent Total Synthesis

Yu, Biao; Wang, Shengyang

doi:10.1002/tcr.202100057

“…8a), supported using X-ray crystallography. 63,65 More recently, the chemical synthesis of miharamycin B (6) and analogues was reported by Wang and Liu. 66 Starting from enantiopure (R)-Garner's aldehyde (49) and 3-bromofuran (50), a 20-step asymmetric de novo approach was designed (Fig.…”

Section: Peptidyl Purine Nucleosidesmentioning

confidence: 99%

Purine nucleoside antibiotics: recent synthetic advances harnessing chemistry and biology

Motter,

Benckendorff,

Westarp

et al. 2024

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Identification of Kibdelomycin and Related Biosynthetic Gene Clusters and Characterization of the C‐Branching of Amycolose

Krug,

Bjarnesen,

Lanza

et al. 2024

Angewandte Chemie

0

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Many bacterial natural products contain C‐branched sugars, including components from the outer cell wall or antibiotically active metabolites. The enzymatic C‐branching of keto sugars leading to longer side chains (≥C2), is catalyzed by thiamine diphosphate (ThDP)‐dependent enzymes. Chiral tertiary α‐hydroxy ketones are formed in this process. The ThDP enzymes that catalyze C‐branching reactions belong to one of three enzymatic superfamilies: decarboxylases, transketolases, and α‐ketoacid dehydrogenases 2, but branching of keto sugars has only been demonstrated for decarboxylases. In this study, we showed that an α‐ketoacid dehydrogenase is responsible for C‐branching of the deoxyketo sugar amycolose in the biosynthesis of kibdelomycin in Kibdelosporangium sp. MA7385. In addition, we characterized an amino transferase in the same biosynthetic gene cluster (BGC) that accepts a sterically demanding tertiary α‐hydroxy ketone in a downstream reaction. Subsequently, we identified approximately 400 similar BGCs in silico, suggesting that there is a large diversity of possible ThDP‐dependent enzymes catalyzing the C‐branching of keto sugars and subsequent modifications.

show abstract

Identification of Kibdelomycin and Related Biosynthetic Gene Clusters and Characterization of the C‐Branching of Amycolose

Krug,

Bjarnesen,

Lanza

et al. 2024

Angew Chem Int Ed

0

View full text Add to dashboard Cite

Many bacterial natural products contain C‐branched sugars, including components from the outer cell wall or antibiotically active metabolites. The enzymatic C‐branching of keto sugars leading to longer side chains (≥C2), is catalyzed by thiamine diphosphate (ThDP)‐dependent enzymes. Chiral tertiary α‐hydroxy ketones are formed in this process. The ThDP enzymes that catalyze C‐branching reactions belong to one of three enzymatic superfamilies: decarboxylases, transketolases, and α‐ketoacid dehydrogenases 2, but branching of keto sugars has only been demonstrated for decarboxylases. In this study, we showed that an α‐ketoacid dehydrogenase is responsible for C‐branching of the deoxyketo sugar amycolose in the biosynthesis of kibdelomycin in Kibdelosporangium sp. MA7385. In addition, we characterized an amino transferase in the same biosynthetic gene cluster (BGC) that accepts a sterically demanding tertiary α‐hydroxy ketone in a downstream reaction. Subsequently, we identified approximately 400 similar BGCs in silico, suggesting that there is a large diversity of possible ThDP‐dependent enzymes catalyzing the C‐branching of keto sugars and subsequent modifications.

show abstract

Solving the Structural Puzzles of Amipurimycin and Miharamycins Enabled by Stereodivergent Total Synthesis

Cited by 4 publications

References 63 publications

Purine nucleoside antibiotics: recent synthetic advances harnessing chemistry and biology

Purine nucleoside antibiotics: recent synthetic advances harnessing chemistry and biology

Identification of Kibdelomycin and Related Biosynthetic Gene Clusters and Characterization of the C‐Branching of Amycolose

Identification of Kibdelomycin and Related Biosynthetic Gene Clusters and Characterization of the C‐Branching of Amycolose

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