Discovery of the leinamycin family of natural products by mining actinobacterial genomes

Pan, Guohui,Xu, Zhengren,Guo, Zhikai,Hindra,Ma, Ming,Yang, Dong,Zhou, Hao,Gansemans, Yannick,Zhu, Xiangcheng,Huang, Yong,Zhao, Li-Xing,Jiang, Yi,Cheng, Jinhua,Van Nieuwerburgh, Filip,Suh, Joo-Won,Duan National Academy of Sciences 2017 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.114 No.52

<P>Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.</P>

Association between the Interleukin-17A -197G>A (rs2275913) Polymorphism and Risk of Digestive Cancer

Duan, Yin,Shi, Ji-Nan,Pan, Chi,Chen, Hai-Long,Zhang, Su-Zhan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation and progression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913) polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the role of this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic review and meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving 3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of the association. The results of overall analyses indicated that the variant A allele was associated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA: OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specific cancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28; AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, there was evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG: OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13-1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasian populations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). In conclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to an increased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastric cancer.

Mechanism of Synergetic Growth of Flexibility and Strength of Biomimetic Nanocomposite Fibre

Xiangyu Duan,Pan Li,Jingyu Ouyang,Zichen Gao,Jiaxin Liu,Jie Wang,Zhigang Xia,Weilin Xu 한국섬유공학회 2022 Fibers and polymers Vol.23 No.3

Nanocomposites with carbon nanotubes (CNTs) can combine the stiffness and multi-functionality of carbonnanotubes with the advantages of high toughness and processability of polymers giving rise to properties different from thatof general composites. However, when the content of CNTs increases gradually, the flexibility of the composite fibre canreduce. In this paper, we propose a simple method of softening the composite fibre via dimensional helical deformation offibre inner macromolecule bundles to avoid the deterioration of fibre flexibility. The theoretical simulations were conductedto predict proper helical deformations of the single fibre to increase fibre softness, followed by practical softening of thepolyvinylidene difluoride (PVDF)/CNTs composite by tensional twisting of the single fibres. The fibres with and withouttensional twisting were tested by Fourier-transformed infrared spectroscopy, scanning electron microscopy, X-ray diffractionand mechanical drawing. Results showed the reinforcement of the PVDF/multi-walled CNTs composite fibres (tensilestrength enhanced from 4.71 to 5.19 cN/dtex) with an evident softness reduction (initial modulus increased from 16.8 to20.52 cN/dtex) as the CNTs content increased from 0 to 1.5 wt%. After the tensional twisting, the initial modulus of thecomposite fibre was reduced by 62.5 % while the fibre strength remained reinforced because biomimetic helix formationimproved the internal structure deformation ability of the fibre.

Contributed Mini Review : New paradigms on siRNA local application

( Meng Pan ),( Jin Wen Ni ),( Hui Ming He ),( Shan Gao ),( Xiao Hong Duan ) 생화학분자생물학회 2015 BMB Reports Vol.48 No.3

Small interfering RNA (siRNA) functions through pairing with specific mRNA sequences and results in the mRNA`s degradation. It is a potential therapeutic approach for many diseases caused by altered gene expression. The delivery of siRNA is still a major problem due to its rapid degradation in the circulation. Various strategies have been proposed to help with the cellular uptake of siRNA and short or small hairpin RNA (shRNA). Here, we reviewed recently published data regarding local applications of siRNA. Compared with systemic delivery methods, local delivery of siRNA/shRNA has many advantages, such as targeting the specific tissues or organs, mimicking a gene knockout effect, or developing certain diseases models. The eye, brain, and tumor tissues are ‘hot’ target tissues/ organs for local siRNA delivery. The siRNA can be delivered locally, in naked form, with chemical modifications, or in formulations with viral or non-viral vectors, such as liposomes and nanoparticles. This review provides a comprehensive overview of RNAi local administration and potential future applications in clinical treatment. [BMB Reports 2015; 48(3): 147-152]

Polymethoxylated Flavone Extracts from Citrus Peels for Use in the Functional Food and Nutraceutical Industry

Xiaolin Yao,Siyi Pan,Chunhong Duan,Fang Yang,Gang Fan,Xinrong Zhu,Shuzhen Yang,Xiaoyun Xu 한국식품과학회 2009 Food Science and Biotechnology Vol.18 No.5

Polymethoxylated flavones (PMFs) extracted from Citrus sinensis ‘Jincheng’ peel were characterized by chromatographic and spectroscopic techniques. Seven individual PMF were identified. 3, 3’, 4’, 5, 6, 7-hexamethoxyflavone (HEX), nobiletin (NOB), heptamethoxyflavone (HEP), 5-demethylnobiletin (DN), and tangeretin (TAN) were characterized through electrospray ionization mass spectrometry (ESI-MS) in positive mode of protonated molecular ions [M+H]?, the diagnostic fragment ions, together with the UV-Vis spectra and high performance liquid chromatography (HPLC) elution order from literature data. Sinensetin (SIN) and tetramethyl-O-scutellarein (SCU) were isolated and identified through their MS, ¹H nuclear magnetic resonance (NMR) and UV-Vis spectral studies. The levels of PMFs in peels from different cultivars of citrus fruits grown in China were determined for the first time. The results showed that C. aurantium ‘Bitter orange’ peel was the most promising variety for HEP. C. sinensis peel was a good source for SIN and SCU.

Strategy for Fabricating Wafer-Scale Platinum Disulfide

Xu, Hongjun,Huang, Hsin-Pan,Fei, HaiFeng,Feng, Jiafeng,Fuh, Huei-Ru,Cho, Jiung,Choi, Miri,Chen, Yanhui,Zhang, Lei,Chen, Dengyun,Zhang, Duan,Coileá,in, Cormac Ó,Han, Xiufeng,Chang, Ching-Ra American Chemical Society 2019 ACS APPLIED MATERIALS & INTERFACES Vol.11 No.8

<P>PtS<SUB>2</SUB> is a newly developed group 10 2D layered material with high carrier mobility, wide band gap tunability, strongly bound excitons, symmetrical metallic and magnetic edge states, and ambient stability, making it attractive in nanoelectronic, optoelectronic, and spintronic fields. To the aim of application, a large-scale synthesis is necessary. For transition-metal dichalcogenide (TMD) compounds, a thermally assisted conversion method has been widely used to fabricate wafer-scale thin films. However, PtS<SUB>2</SUB> cannot be easily synthesized using the method, as the tetragonal PtS phase is more stable. Here, we use a specified quartz part to locally increase the vapor pressure of sulfur in a chemical vapor deposition furnace and successfully extend this method for the synthesis of PtS<SUB>2</SUB> thin films in a scalable and controllable manner. Moreover, the PtS and PtS<SUB>2</SUB> phases can be interchangeably converted through a proposed strategy. Field-effect transistor characterization and photocurrent measurements suggest that PtS<SUB>2</SUB> is an ambipolar semiconductor with a narrow band gap. Moreover, PtS<SUB>2</SUB> also shows excellent gas-sensing performance with a detection limit of ∼0.4 ppb for NO<SUB>2</SUB>. Our work presents a relatively simple way of synthesizing PtS<SUB>2</SUB> thin films and demonstrates their promise for high-performance ultrasensitive gas sensing, broadband optoelectronics, and nanoelectronics in a scalable manner. Furthermore, the proposed strategy is applicable for making other PtX<SUB>2</SUB> compounds and TMDs which are compatible with modern silicon technologies.</P> [FIG OMISSION]</BR>

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative

Wang, Xue-Jian,Duan, Yu,Li, Zong-Tao,Feng, Jin-Hong,Pan, Xiang-Po,Zhang, Xiu-Rong,Shi, Li-Hong,Zhang, Tao Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Multi-target drug design, in which drugs are designed as single molecules to simultaneously modulate multiple physiological targets, is an important strategy in the field of drug discovery. QT-011, a tamibarotene-furoxan derivative, was here prepared and proposed to exert synergistic effects on antileukemia by releasing nitric oxide and tamibarotene. Compared with tamibarotene itself, QT-011 displayed stronger antiproliferative effects on U937 and HL-60 cells and was more effective evaluated in a nude mice U937 xenograft model in vivo. In addition, QT-011 could release nitric oxide which might contribute to the antiproliferative activity. Autodocking assays showed that QT-011 fits well with the hydrophobic pocket of retinoic acid receptors. Taken together, these results suggest that QT-011 might be a highly effective derivative of tamibarotene and a potential candidate compound as antileukemia agent.

Optimization on Anthocyanins Extraction from Wine Grape Skins Using Orthogonal Test Design

Zheng Li,Qiuhong Pan,Xiangyun Cui,Changqing Duan 한국식품과학회 2010 Food Science and Biotechnology Vol.19 No.4

To optimize the extraction of anthocyanins from grape skins, orthogonal test with 4 factors and 3 levels was designed and the analysis of extracts was conducted using high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The results showed that the optimal extraction for obtaining the highest amounts of anthocyanins was carried out by formic acid/methanol solvent (5/95, v/v), with ultrasonication for 10 min, extraction temperature at 25℃, and extraction time for 1.5 hr. The precision and accuracy of this method were established. This work will provide a basis for further study involving in anthocyanins of grape berries.

Evolution of 49 Phenolic Compounds in Shortly-aged Red Wines Made from Cabernet Gernischt (Vitis vinifera L. cv.)

Zheng Li,Qiu-Hong Pan,Zan-Min Jin,Jian-Jun He,Na-Na Liang,Chang-Qing Duan 한국식품과학회 2009 Food Science and Biotechnology Vol.18 No.4

A total of 49 phenolic compounds were identified from the aged red wines made from Cabernet Gernischt (Vitis vinifera L. cv.) grapes, a Chinese characteristic variety, including 13 anthocyanins, 4 pryanocyanins, 4 flavan-3-ol monomers, 6 flavan-3-ol polymers, 7 flavonols, 6 hydroxybenzoic acids, 5 hydroxycinnamic acids, 3 stilbenes, and 1 polymeric pigment. Evolution of these compounds was investigated in wines aged 1 to 13 months. Variance analysis showed that the levels of most phenolics existed significant difference in between wines aged 3 and 9 months. Cluster analysis indicated that 2 groups could be distinguished, one corresponding to wines aged 1 to 3 months and the other to wines aged 4 to 13 months. It was thus suggested that there were 2 key-stages for the development of fine wine quality, at the aged 3 and 9 months, respectively. This work would provide some helpful information for quality control in wine production.

Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration

Jianle Wang,Majid Nisar,Chongan Huang,Xiangxiang Pan,Dongdong Lin,Gang Zheng,Haiming Jin,Deheng Chen,Naifeng Tian,Qianyu Huang,Yue Duan,Yingzhao Yan,Ke Wang,Congcong Wu,Jianing Hu,Xiaolei Zhang,Xiangy 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD. We assessed SIRT3 expression in degenerative nucleus pulposus (NP) tissues and oxidative stressinduced nucleus pulposus cells (NPCs). SIRT3 was knocked down by lentivirus and activated by honokiol to determine its role in oxidative stress-induced NPCs. The mechanism by which honokiol affected SIRT3 regulation was investigated in vitro, and the therapeutic potential of honokiol was assessed in vitro and in vivo. We found that the expression of SIRT3 decreased with IVDD, and SIRT3 knockdown reduced the tolerance of NPCs to oxidative stress. Honokiol (10 μM) improved the viability of NPCs under oxidative stress and promoted their properties of anti-oxidation, mitochondrial dynamics and mitophagy in a SIRT3-dependent manner. Furthermore, honokiol activated SIRT3 through the AMPKPGC- 1α signaling pathway. Moreover, honokiol treatment ameliorated IVDD in rats. Our study indicated that SIRT3 is involved in IVDD and showed the potential of the SIRT3 agonist honokiol for the treatment of IVDD.