Am-aza-ing antidiabetic: Mulberry dehydrogenase MnGUTB1 contributes to the biosynthesis of 1-deoxynojirimycin

Straube, Henryk

doi:10.1093/plphys/kiad140

Cited by 3 publications

(4 citation statements)

References 9 publications

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“…Due to its unique structure and significant pharmacological activities, DNJ has been attracting much attention. Although there are two speculations about the biosynthetic pathway of DNJ in mulberry leaves, the mining of CPR functional genes in mulberry leaves is the key to achieving the heterologous synthesis of DNJ, whether it originates from lysine or glucose [12][13][14].…”

Section: Discussionmentioning

confidence: 99%

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Mining and functional characterization of NADPH-cytochrome P450 reductases of the DNJ biosynthetic pathway in mulberry leaves

Liao,

Du,

Wan

et al. 2024

BMC Plant Biol

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Background 1-Deoxynojirimycin (DNJ), the main active ingredient in mulberry leaves, with wide applications in the medicine and food industries due to its significant functions in lowering blood sugar, and lipids, and combating viral infections. Cytochrome P450 is a key enzyme for DNJ biosynthesis, its activity depends on the electron supply of NADPH-cytochrome P450 reductases (CPRs). However, the gene for MaCPRs in mulberry leaves remains unknown. Results In this study, we successfully cloned and functionally characterized two key genes, MaCPR1 and MaCPR2, based on the transcriptional profile of mulberry leaves. The MaCPR1 gene comprised 2064 bp, with its open reading frame (ORF) encoding 687 amino acids. The MaCPR2 gene comprised 2148 bp, and its ORF encoding 715 amino acids. The phylogenetic tree indicates that MaCPR1 and MaCPR2 belong to Class I and Class II, respectively. In vitro, we found that the recombinant enzymes MaCPR2 protein could reduce cytochrome c and ferricyanide using NADPH as an electron donor, while MaCPR1 did not. In yeast, heterologous co-expression indicates that MaCPR2 delivers electrons to MaC3'H hydroxylase, a key enzyme catalyzing the production of chlorogenic acid from 3-O-p-coumaroylquinic acid. Conclusions These findings highlight the orchestration of hydroxylation process mediated by MaCPR2 during the biosynthesis of secondary metabolite biosynthesis in mulberry leaves. These results provided a foundational understanding for fully elucidating the DNJ biosynthetic pathway within mulberry leaves.

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Section: Discussionmentioning

confidence: 99%

“…The polyhydroxy structure endows it with various pharmacological activity [11]. There are two speculations about the biosynthesis pathway of DNJ in mulberry leaves [12][13][14]. Theory of biosynthesis mechanism based on secondary metabolites of alkaloids in plants.…”

Section: Introductionmentioning

confidence: 99%

Mining and functional characterization of NADPH-cytochrome P450 reductases of the DNJ biosynthetic pathway in mulberry leaves

Liao,

Du,

Wan

et al. 2024

BMC Plant Biol

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“…Derivation with 9-fl uorenylmethyl chloroformate and HPLC [211] Precolumn derivation (6-aminoquinoiyi-Nhydroxysuccinimidyl carbamate) and HPLC [212] Microwave-assisted extraction [213] Derivation with 9-fl uorenylmethyl succinimidyl carbonate and HPLC [214] HPLC analysis of 146 species and subspecies (India) [215] Determination in Italian cultivars by HPLC-MS [216] Determination in antidiabetic Fu-Zhu-Jiang-Tang tablets by GC-MS [217] Determination in dietary supplements by ATR-FTIR [218] HPLC analysis of UVC-irradiated M. alba leaves that increased DNJ content 4-fold [219] Production enhancement by leaves fermentation with G. lucidum [220] Fermentation of leaves powder with four species of bacteria increased the concentration of DNJ by all of them, and W. anomalus was highest [221] Figure 12 Short versions of two DNJ biosynthetic pathways [222,223].…”

Section: Analysis or Production Methods Referencesmentioning

confidence: 99%

“…Several publications proposed the biosynthesis of DNJ. One of these presented 11 biosynthetic steps starting from aspartic acid [222], while starting from D-glucose required only 6 steps, and the authors named it "am-aza-ing" [223]. See a short version of these biosynthetic paths in fi gure 12.…”

Section: Figure 11mentioning

confidence: 99%

Morus Plant Genus: Superb Antidiabetic Activity and Outstanding Source of Nutrients

Azab¹

2023

J Biomed Res Environ Sci

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The plant genus Morus (Mulberry) has been used by humans for many centuries. All parts of the trees are used, but the fruits have the highest nutritional values. Most of the species of this genus were studied for various medicinal and biological activities, as well as many other properties, including chemical composition. Two species, Morus alba and Morus nigra were very extensively investigated, and research reports about them continue to be published very frequently. The chemistry of this plant genus is fascinating. It includes numerous natural products with unique structures and structure-sub-units, making them excellent candidates as organic synthesis starting materials. Many review articles were published about the Morus genus and some of its species, but this article is the most comprehensive regarding antidiabetic activity and insulin regulation. Active natural products are responsible for these activities will be presented, as well as possible and proposed mechanisms of action. Ethnobotanical and ethnomedicinal information related to the antidiabetic activity will be briefly presented. In addition, a thorough discussion section will lead to conclusions, some future directions, and recommendations for research.

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Mining and characterization of a novel cytochrome P450 MaCYP71BG22 involved in the C4-stereoselective hydroxylation of 1-deoxynojirimycin biosynthesis in mulberry leaves

Liao,

Wu,

Fan

et al. 2024

International Journal of Biological Macromolecules

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Am-aza-ing antidiabetic: Mulberry dehydrogenase MnGUTB1 contributes to the biosynthesis of 1-deoxynojirimycin

Cited by 3 publications

References 9 publications

Mining and functional characterization of NADPH-cytochrome P450 reductases of the DNJ biosynthetic pathway in mulberry leaves

Mining and functional characterization of NADPH-cytochrome P450 reductases of the DNJ biosynthetic pathway in mulberry leaves

Morus Plant Genus: Superb Antidiabetic Activity and Outstanding Source of Nutrients

Mining and characterization of a novel cytochrome P450 MaCYP71BG22 involved in the C4-stereoselective hydroxylation of 1-deoxynojirimycin biosynthesis in mulberry leaves

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