• Title/Summary/Keyword: synthetic biology

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Advances in the Structures, Pharmacological Activities, and Biosynthesis of Plant Diterpenoids

  • Leilei Li;Jia Fu;Nan Liu
    • Journal of Microbiology and Biotechnology
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    • v.34 no.8
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    • pp.1563-1579
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    • 2024
  • More and more diterpenoids have attracted extensive attention due to the diverse chemical structures and excellent biological activities, and have been developed into clinical drugs or consumer products. The vast majority of diterpenoids are derived from plants. With the long-term development of plant medicinal materials, the natural resources of many plant diterpenoids are decreasing, and the biosynthetic mechanism of key active components has increasingly become a research hotspot. Using synthetic biology to engineer microorganisms into "cell factories" to produce the desired compounds is an essential means to solve these problems. In this review, we depict the plant-derived diterpenoids from chemical structure, biological activities, and biosynthetic pathways. We use representative plant diterpenes as examples to expound the research progress on their biosynthesis, and summarize the heterologous production of plant diterpenoids in microorganisms in recent years, hoping to lay the foundation for the development and application of plant diterpenoids in the future.

Effects of the Synthetic Coprisin Analog Peptide, CopA3 in Pathogenic Microorganisms and Mammalian Cancer Cells

  • Kim, In-Woo;Kim, Soon-Ja;Kwon, Yong-Nam;Yun, Eun-Young;Ahn, Mi-Young;Kang, Dong-Chul;Hwang, Jae-Sam
    • Journal of Microbiology and Biotechnology
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    • v.22 no.1
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    • pp.156-158
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    • 2012
  • A synthetic coprisin analog peptide, 9-mer dimer CopA3 (CopA3) was designed based on a defensin-like peptide, Coprisin, isolated from the bacteria-immunized dung beetle Copris tripartitus. Here, CopA3 was investigated for its antimicrobial activity and cancer cell growth inhibition. CopA3 showed antimicrobial activities against various pathogenic bacteria and yeast fungus with MIC values in 2~32 ${\mu}M$ ranges, and inhibited the cell viabilities of pancreatic and hepatocellular cancer cells, except MIA-Paca2, Hep3B, and HepG2 cells, in a dose-dependent manner. The average $IC_{50}$ values of CopA3 against pancreatic and hepatocellular cancer cells were 61.7 ${\mu}M$ and 67.8 ${\mu}M$, respectively. The results indicate that CopA3 has potential in the treatments of pancreatic and hepatocellular cancers as well as microorganism infection disease.

Effects of 4-Nitroquinoline-1-oxide on Synthetic Patterns of Protein and Glycosaminoglycan during Chick Development (계배 발생중의 단백질 및 당점액질 합성에 대한 4NQO의 영향)

  • Hah, Jae-Chung;Han, Bog-Key
    • The Korean Journal of Zoology
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    • v.26 no.4
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    • pp.283-294
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    • 1983
  • In order to study the change of protein synthesis in developing chick embryo under the influence of carcinogenic substances, we introduced a kind of potent carcinogen, 4-nitroquinoline-1-oxide (4 NQO) to the yolk sac of developing chick embryo. There are changes of synthetic pattern of protein abreast with proceeding of development is each tissue. Protein synthesis in samples which was treated with 4NQO was decreased as compared with untreated control samples. There are tissue specificity in 4NQO effect, showing the apparent decreasing at the 24 hr after drug treatment in the lung and gizzard muscle but not in heart muscle. The results in the present study suggested that 4NQO treated samples was decreased as compared with control samples. From the above data we could know that 4NQO also affected the synthesis of glycosaminoglycan.

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Microbial linguistics: perspectives and applications of microbial cell-to-cell communication

  • Mitchell, Robert J.;Lee, Sung-Kuk;Kim, Tae-Sung;Ghim, Cheol-Min
    • BMB Reports
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    • v.44 no.1
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    • pp.1-10
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    • 2011
  • Inter-cellular communication via diffusible small molecules is a defining character not only of multicellular forms of life but also of single-celled organisms. A large number of bacterial genes are regulated by the change of chemical milieu mediated by the local population density of its own species or others. The cell density-dependent "autoinducer" molecules regulate the expression of those genes involved in genetic competence, biofilm formation and persistence, virulence, sporulation, bioluminescence, antibiotic production, and many others. Recent innovations in recombinant DNA technology and micro-/nano-fluidics systems render the genetic circuitry responsible for cell-to-cell communication feasible to and malleable via synthetic biological approaches. Here we review the current understanding of the molecular biology of bacterial intercellular communication and the novel experimental protocols and platforms used to investigate this phenomenon. A particular emphasis is given to the genetic regulatory circuits that provide the standard building blocks which constitute the syntax of the biochemical communication network. Thus, this review gives focus to the engineering principles necessary for rewiring bacterial chemo-communication for various applications, ranging from population-level gene expression control to the study of host-pathogen interactions.

Determination of the Synthetic Time and the Transport Pattern of Vicilin and Legumin in Ginseng Endosperm Cell Using Double Immunogold Labeling (이중 면역금입자 표지법을 이용한 인삼 배유세포내 Vicilin과 Legumin의 합성시기 및 수송방식)

  • Lee, Chang-Seob;Yu, Seong-Cheol;Kim, Woo-Kap
    • Journal of Ginseng Research
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    • v.19 no.3
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    • pp.267-274
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    • 1995
  • Vicilin and legumin, the storage Proteins of seed, were Purified from ginseng (Panax ginseng C.A. Meyer) endosperm cells. They were immunized in rabbits, and antibodies were raised respectively. Using these two antibodies, double immunogold labeling of vicilin and legumin was carried out to determine the gap of synthetic time and the transport pattern of vicilin and legumin in the ginseng endosperm cells. Vicilin and legumin were synthesized at the same time at early embryo developmental stage. They were secreted from the Golgi bodies and accumulated into the small vacuoles. As the endosperm cells developed, vicilin and legumin localized in the small vacuoles were gradually transported toward the large central vacuole where they were stored. Protein bodies were derived from the vacuoles filled with proteins and distributed in the endosperm cells of mature red seed. Protein bodies were various in size from 1 to 8 ${\mu}{\textrm}{m}$ in which vicilin and legumin were mixed each other. The number of small particles labeled on the vicilin was greater than that of large particles labeled on the legumin in the protein bodies indicating that the amount of vicilin is higher than that of legumin in the protein bodies.

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Pharmacophore Modeling and Molecular Dynamics Simulation to Find the Potent Leads for Aurora Kinase B

  • Sakkiah, Sugunadevi;Thangapandian, Sundarapandian;Kim, Yong-Seong;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.33 no.3
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    • pp.869-880
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    • 2012
  • Identification of the selective chemical features for Aurora-B inhibitors gained much attraction in drug discovery for the treatment of cancer. Hence to identify the Aurora-B critical features various techniques were utilized such as pharmacophore generation, virtual screening, homology modeling, molecular dynamics, and docking. Top ten hypotheses were generated for Aurora-B and Aurora-A. Among ten hypotheses, HypoB1 and HypoA1 were selected as a best hypothesis for Aurora-B and Aurora-A based on cluster analysis and ranking score, respectively. Test set result revealed that ring aromatic (RA) group in HypoB1 plays an essential role in differentiates Aurora-B from Aurora-A inhibitors. Hence, HypoB1 used as 3D query in virtual screening of databases and the hits were sorted out by applying drug-like properties and molecular docking. The molecular docking result revealed that 15 hits have shown strong hydrogen bond interactions with Ala157, Glu155, and Lys106. Hence, we proposed that HypoB1 might be a reasonable hypothesis to retrieve the structurally diverse and selective leads from various databases to inhibit Aurora-B.

Oxidation-Induced Conformational Change of a Prokaryotic Molecular Chaperone, Hsp33, Monitored by Selective Isotope Labeling

  • Lee, Yoo-Sup;Ryu, Kyoung-Seok;Lee, Yuno;Kim, Song-Mi;Lee, Keun-Woo;Won, Hyung-Sik
    • Journal of the Korean Magnetic Resonance Society
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    • v.15 no.2
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    • pp.137-145
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    • 2011
  • Hsp33, a prokaryotic molecular chaperone, exerts holdase activity in response to oxidative stress. In this study, the stepwise conformational change of Hsp33 upon oxidation was monitored by NMR. In order to overcome its high molecular weight (33 kDa as a monomer and 66 kDa as a dimer), spectra were simplified using a selectively [$^{15}N$]His-labeled protein. All of the eight histidines were observed in the TROSY spectrum of the reduced Hsp33. Among them, three peaks showed dramatic resonance shifts dependent on the stepwise oxidation, indicating a remarkable conformational change. The results suggest that unfolding of the linker domain is associated with dimerization, but not entire region of the linker domain is unfolded.

Genetic Function Approximation and Bayesian Models for the Discovery of Future HDAC8 Inhibitors

  • Thangapandian, Sundarapandian;John, Shalini;Lee, Keun-Woo
    • Interdisciplinary Bio Central
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    • v.3 no.4
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    • pp.15.1-15.11
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    • 2011
  • Background: Histone deacetylase (HDAC) 8 is one of its family members catalyzes the removal of acetyl groups from N-terminal lysine residues of histone proteins thereby restricts transcription factors from being expressed. Inhibition of HDAC8 has become an emerging and effective anti-cancer therapy for various cancers. Application computational methodologies may result in identifying the key components that can be used in developing future potent HDAC8 inhibitors. Results: Facilitating the discovery of novel and potential chemical scaffolds as starting points in the future HDAC8 inhibitor design, quantitative structure-activity relationship models were generated with 30 training set compounds using genetic function approximation (GFA) and Bayesian algorithms. Six GFA models were selected based on the significant statistical parameters calculated during model development. A Bayesian model using fingerprints was developed with a receiver operating characteristic curve cross-validation value of 0.902. An external test set of 54 diverse compounds was used in validating the models. Conclusions: Finally two out of six models based on their predictive ability over the test set compounds were selected as final GFA models. The Bayesian model has displayed a high classifying ability with the same test set compounds and the positively and negatively contributing molecular fingerprints were also unveiled by the model. The effectively contributing physicochemical properties and molecular fingerprints from a set of known HDAC8 inhibitors were identified and can be used in designing future HDAC8 inhibitors.

Production rind Characterization of the Polyclonal Anti-peptide Antibody for $\beta$-adrenergic Receptor

  • Kim, Hee-Jin;Shin, Chan-Young;Sang Bong lee;Ko, Kwang-Ho
    • Biomolecules & Therapeutics
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    • v.2 no.4
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    • pp.303-309
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    • 1994
  • The analysis of membrane receptors for hormones and neurotransmitters has progressed considerably by pharmacological and biochemical means and more recently through the use of specific antibodies. Two kinds of antibodies could be produced, one is from synthetic peptides and the other from proteins such as purified receptor. Anti-peptide antibodies gave some advantages; epitope is evident and also receptor purification in quantity is not prerequisite. It can be also applied to the study of receptor structure-activity relationship. The purpose of the present study was 1) to produce and characterize a polyclonal antibody against a synthetic $\beta$2-adrenergic receptor peptide(Phe-Gly-Asn-Phe-Trp-Cys-Phe-Trp-Thr-Ser-Ile-Asp-Val-Leu) and 2) to determine the effects of this antibody on the $\beta$-adrenergic receptor ligand interaction. The peptide sequence contains an amino acid residue such as Asp-113 which was identified as one of important component for receptor-ligand interaction in site-directed mutagenesis studies. Production of antibody was performed by immunization of rabbits through popliteal lymph node with the peptide coupled with Keyhole Limpet Hemocyanin (KLH). The titer of antibody against this peptide was 1 : 1000. The anti-peptide antibody was able to detect a 67 kDa protein band in western blot corresponding to the molecular weight of the $\beta$-adrenergic receptor in partially purified receptor fraction derived from guinea pig lung. The antisera inhibited the specific binding of [$^3$H]dihydroalprenolol to $\beta$-adrenergic receptor in a concentration-dependent manner. The results from this study suggest that the peptide sequence selected in the present study is important for the receptor ligand interaction.

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