Recent Progress in Unusual Carbohydrate-Containing Natural Products Biosynthesis

Zhang, Jiawei; Fan, Po-Hsun; Lin, Grace C.; Chang, Wei‐chen; Liu, Hung‐wen

doi:10.1016/b978-0-12-409547-2.14698-0

Cited by 3 publications

(3 citation statements)

References 356 publications

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“…Apramycin ( 1 ) isolated from Streptoalloteichus tenebrarius (S. tenebrarius) and S. hindustanus − is an aminoglycoside − commonly used as a veterinary antibiotic . Its mode of action involves inhibition of bacterial protein synthesis by blocking the ribosomal translocation step .…”

Section: Introductionmentioning

confidence: 99%

Biosynthetic Origin of the Octose Core and Its Mechanism of Assembly during Apramycin Biosynthesis

Fan,

Sato,

Yeh

et al. 2023

J. Am. Chem. Soc.

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Apramycin is an aminoglycoside antibiotic isolated from Streptoalloteichus tenebrarius and S. hindustanus that has found clinical use in veterinary medicine. The apramycin structure is notable for its atypical eight-carbon bicyclic dialdose (octose) moiety. While the apramycin biosynthetic gene cluster (apr) has been identified and several of the encoded genes functionally characterized, how the octose core itself is assembled has remained elusive. Nevertheless, recent gene deletion studies have hinted at an N-acetyl aminosugar being a key precursor to the octose, and this hypothesis is consistent with the additional feeding experiments described in the present report. Moreover, bioinformatic analysis indicates that AprG may be structurally similar to GlcNAc-2-epimerase and hence recognize GlcNAc or a structurally similar substrate suggesting a potential role in octose formation. AprG with an extended N-terminal sequence was therefore expressed, purified, and assayed in vitro demonstrating that it does indeed catalyze a transaldolation reaction between GlcNAc or GalNAc and 6′-oxo-lividamine to afford 7′-N-acetyldemethylaprosamine with the same 6′-R and 7′-S stereochemistry as those observed in the apramycin product. Biosynthesis of the octose core in apramycin thus proceeds in the [6 + 2] manner with GlcNAc or GalNAc as the two-carbon donor, which has not been previously reported for biological octose formation, as well as novel inverting stereochemistry of the transferred fragment. Consequently, AprG appears to be a new transaldolase that lacks any apparent sequence similarity to the currently known aldolases and catalyzes a transaldolation for which there is no established biological precedent.

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Section: Introductionmentioning

confidence: 99%

Biosynthetic Origin of the Octose Core and Its Mechanism of Assembly during Apramycin Biosynthesis

Fan,

Sato,

Yeh

et al. 2023

J. Am. Chem. Soc.

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“…Many reviews dealing with nucleoside antivirals were published. Recent examples are accounts on fluorinated nucleosides [ 10 , 11 ], 4′-modified nucleosides [ 12 ], oxetanocin [ 13 , 14 ], marketed nucleosides [ 15 ], antiviral nucleosides and analogues [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], and the chemistry of nucleoside drugs [ 36 , 37 , 38 ]. However, these reviews predominantly consider chemical and structural aspects, with some discussion on the main nucleoside mechanisms of antiviral action [ 21 , 22 , 24 , 29 , 30 , 34 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Molecular Mechanisms of Nucleoside Antivirals

Kamzeeva,

Aralov,

Alferova

et al. 2023

CIMB

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The search for new drugs has been greatly accelerated by the emergence of new viruses and drug-resistant strains of known pathogens. Nucleoside analogues (NAs) are a prospective class of antivirals due to known safety profiles, which are important for rapid repurposing in the fight against emerging pathogens. Recent improvements in research methods have revealed new unexpected details in the mechanisms of action of NAs that can pave the way for new approaches for the further development of effective drugs. This review accounts advanced techniques in viral polymerase targeting, new viral and host enzyme targeting approaches, and prodrug-based strategies for the development of antiviral NAs.

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“…Carbohydrates are ubiquitously found in nature and a great abundance of the Earth's biomass is glycosylated (Thibodeaux et al, 2007;Zhang et al, 2020 ). In addition to the most found hexose and pentose, the versatile biological properties of heptose-containing glycoconjugates have been elaborated simultaneously (Guo et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

A conservative distribution of tridomain NDP-heptose synthetases in actinobacteria

Tang

Wang

et al. 2021

Sci. China Life Sci.

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Heptoses are important structural components of Gram-negative bacterium cell wall and participate in bacterial colonization, infection, and immune recognition. Current knowledge of NDP-heptose originating from d -sedoheptulose 7-phosphate in Grampositive bacterium remains limited. Here, in silico analysis suggested that the special tridomain NDP-heptose synthetases with isomerase, kinase, and nucleotidyltransferase activities are conservatively distributed in Actinobacteria class of Gram-positive bacterium. Enzymatical characterization of the tridomain proteins from different strains showed that they are involved in ADP- d - glycero-β - d - manno -heptose biosynthesis despite the unexpected discovery of kinase activities deficient in some proteins. The presence of three types of NDP-heptose synthetases in Gram-positive bacterium suggests that it is also a rich source of heptoses and the heptose moieties may play important roles in vivo . Our work updates the understanding of NDP-heptose biosynthesis in Gram-positive bacterium and lays a solid foundation for further physiological function explorations. Supporting Information The supporting information is available online at 10.1007/s11427-021-2000-2. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Recent Progress in Unusual Carbohydrate-Containing Natural Products Biosynthesis

Cited by 3 publications

References 356 publications

Biosynthetic Origin of the Octose Core and Its Mechanism of Assembly during Apramycin Biosynthesis

Biosynthetic Origin of the Octose Core and Its Mechanism of Assembly during Apramycin Biosynthesis

Recent Advances in Molecular Mechanisms of Nucleoside Antivirals

A conservative distribution of tridomain NDP-heptose synthetases in actinobacteria

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