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- Identification of the Genes Involved in 1-Deoxynojirimycin Synthesis in Bacillus subtilis MORI 3K-85
- Kyung-Don Kang , Yong Seok Cho , Ji Hye Song , Young Shik Park , Jae Yeon Lee , Kyo Yeol Hwang , Sang Ki Rhee , Ji Hyung Chung , Ohsuk Kwon , Su-Il Seong
- J. Microbiol. 2011;49(3):431-440. Published online June 30, 2011
- DOI: https://doi.org/10.1007/s12275-011-1238-3
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Abstract
- 1-Deoxynojirimycin (DNJ), a D-glucose analogue with a nitrogen atom substituting for the ring oxygen, is a strong inhibitor of intestinal α-glucosidase. DNJ has several promising biological activities, including its antidiabetic, antitumor, and antiviral activities. Nevertheless, only limited amounts of DNJ are available because it can only be extracted from some higher plants, including the mulberry tree, or purified from the culture broth of several types of soil bacteria, such as Streptomyces sp. and Bacillus sp. In our previous study, a DNJ-producing bacterium, Bacillus subtilis MORI, was isolated from the traditional Korean fermented food Chungkookjang. In the present study, we report the identification of the DNJ biosynthetic genes in B. subtilis MORI 3K-85 strain, a DNJ-overproducing derivate of the B. subtilis MORI strain generated by γ-irradiation. The genomic DNA library of B. subtilis MORI 3K-85 was constructed in Escherichia coli, and clones showing α-glucosidase inhibition activity were selected. After DNA sequencing and a series of subcloning, we were able to identify a putative operon which consists of gabT1, yktc1, and gutB1 genes predicted to encode putative transaminase, phosphatase, and oxidoreductase, respectively. When a recombinant plasmid containing this operon sequence was transformed into an E. coli strain, the resulting transformant was able to produce DNJ into the culture medium. Our results indicate that the gabT1, yktc1, and gutB1 genes are involved in the DNJ biosynthetic pathway in B. subtilis MORI, suggesting the possibility of employing these genes to establish a large-scale microbial DNJ overproduction system through genetic engineering and process optimization.
- Natural Iminosugar Derivatives of 1-Deoxynojirimycin Inhibit Glycosylation of Hepatitis Viral Envelope Proteins
- James R. Jacob , Keith Mansfield , Jung Eun You , Bud C. Tennant , Young Ho Kim
- J. Microbiol. 2007;45(5):431-440.
- DOI: https://doi.org/2593 [pii]
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Abstract
- A silkworm (Bombyx mori L.) extract known to contain naturally occurring iminosugars, including 1-deoxynojirimycin (1-DNJ) derived from the mulberry tree (Morus alba L.), was evaluated in surrogate HCV and HBV in vitro assays. Antiviral activity of the silkworm extract and one of its purified constituents, 1-DNJ, was demonstrated against bovine viral diarrhea virus (BVDV) and GB virus-B (GBV-B), both members of the Flaviviridae family, and against woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV), both members of the Hepadnaviridae family of viruses. The silkworm extract exhibited a 1,300 fold greater antiviral effect against BVDV in comparison to purified 1-DNJ. Glycoprotein processing of BVDV envelope proteins was disrupted upon treatment with the naturally derived components. The glycosylation of the WHV envelope proteins was affected largely by treatment with the silkworm extract than with purified 1-DNJ as well. The mechanism of action for this therapy may lie in the generation of defective particles that are unable to initiate the next cycle of infection as demonstrated by inhibition of GBV-B in vitro. We postulate that the five constituent iminosugars present in the silkworm extract contribute, in a synergistic manner, toward the antiviral effects observed for the inhibition of intact maturation of hepatitis viral particles and may complement conventional therapies. These results indicate that pre-clinical testing of the natural silkworm extract with regards to the efficacy of treatment against viral hepatitis infections can be evaluated in the respective animal models, in preparation for clinical trials in humans.
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