Combining metabolic engineering and biocompatible chemistry for high-yield production of homo-diacetyl and homo-(S,S)-2,3-butanediol

Liu, J.,Chan, S.H.J.,Brock-Nannestad, T.,Chen, J.,Lee, S.Y.,Solem, C.,Jensen, P.R. Academic Press 2016 Metabolic engineering Vol.36 No.-

Biocompatible chemistry is gaining increasing attention because of its potential within biotechnology for expanding the repertoire of biological transformations carried out by enzymes. Here we demonstrate how biocompatible chemistry can be used for synthesizing valuable compounds as well as for linking metabolic pathways to achieve redox balance and rescued growth. By comprehensive rerouting of metabolism, activation of respiration, and finally metal ion catalysis, we successfully managed to convert the homolactic bacterium Lactococcus lactis into a homo-diacetyl producer with high titer (95mM or 8.2g/L) and high yield (87% of the theoretical maximum). Subsequently, the pathway was extended to (S,S)-2,3-butanediol (S-BDO) through efficiently linking two metabolic pathways via chemical catalysis. This resulted in efficient homo-S-BDO production with a titer of 74mM (6.7g/L) S-BDO and a yield of 82%. The diacetyl and S-BDO production rates and yields obtained are the highest ever reported, demonstrating the promising combination of metabolic engineering and biocompatible chemistry as well as the great potential of L. lactis as a new production platform.

Quest for Missing Proteins: Update 2015 on Chromosome-Centric Human Proteome Project

Horvatovich, Pé,ter,Lundberg, Emma K.,Chen, Yu-Ju,Sung, Ting-Yi,He, Fuchu,Nice, Edouard C.,Goode, Robert J.,Yu, Simon,Ranganathan, Shoba,Baker, Mark S.,Domont, Gilberto B.,Velasquez, Erika,Li, D American Chemical Society 2015 Journal of Proteome Research Vol.14 No.9

<P>This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed “missing proteins”) in biological samples that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP’s activities; therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper’s content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wiki (<uri xlink:href='http://c-hpp.webhosting.rug.nl/' xlink:type='simple'>http://c-hpp.webhosting.rug.nl/</uri>) and in the Supporting Information.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jprobs/2015/jprobs.2015.14.issue-9/pr5013009/production/images/medium/pr-2014-013009_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr5013009'>ACS Electronic Supporting Info</A></P>

비육돈에 미생물제제 급여시 분뇨 특성에 미치는 효과

곽정훈,최동윤,박치호,김재환,정광화,양창범,유용희,천현식,라창식,Kwag, J.H.,Choi, D.Y.,Park, Ch.H.,Kim, J.H.,Jeong, K.H.,Yang, Ch.B.,Yoo, Y.H.,Chen, H.S.,La, C.S. 한국축산환경학회 2007 축산시설환경학회지 Vol.13 No.3

본시험은 비육돈사료에 미생물제제를 사료에 미생물제제 A 및 B 0.1 미생물제제 C를 0.2% 혼합 급여할 경우 사료섭취량 및 돈분의 오염물질 배설농도에 미치는 영향을 분석하기 위하여 4처리$\times$반복당 5두로서 총 20두를 공시하여 실시하였는데 그 결과를 요약하면 다음과 같다. 1. 비육돈의 일일 평균사료섭취량은 대조구 3.15 kg/일.두였고 미생물A, B, C구는 각각 3.14kg/일/두, 3.31, 3.42로 미생물제제 C구에서 일일 사료섭취량이 가장 높게 조사되었으며(p<0.05), 2. 일일평균 음수량은 사료섭취량이 높았던 미생물 C구에서 3.95kg/일/두로 가장 높게 조사되었다(p<0.05). 3. 미생물제제 처리구별로 분뇨배설량은 사료섭취량이 높았던 미생물제제 C구에서 가장 많이 배설되는 것으로 조사되었으며(p<0.05), 돈뇨의 배설량도 미생물제제 C구에서 2.23kg/일/두에서 높았다(p<0.05). 4. 돈분뇨의 수분 함량은 및 비료성분인 T-N, $P_{2}O_{5}$, $K_{2}O$ 성분도 처리 간에 큰 차이를 보이지 않았다(p<0.05). 5. 돈분뇨의 평균 BOD 농도는 돈분의 경우 미생물제제 B, C제제 급여구가 유의적으로 높게 조사되었다(p<0.05). 그리고 돈뇨의 BOD의 경우에는 대조구에서 $8,657.5mg/{\ell}$로 가장 높은 것으로 조사되었다(p<0.05). 6. COD 농도는 대조구에서 가장 높게 조사되었으며(p<0.05). 돈뇨의 경우에는 미생물제제 A급여구에서 평균 $9,545mg/{\ell}$로 가장 높았다(p<0.05). 7. SS 농도는 미생물제제 B급여구에서 가장 높게 조사되었으며(p<0.05), 돈분뇨중의 T-N 농도는 처리구간에 유의적인 차이가 나타나지 않았다(p<0.05). 그리고 T-P 농도의 경우에는 미생물제제 C급여구에서 유의적인 차이가 나는 것으로 조사되었다(p<0.05). 이상의 결과를 요약해보면 비육돈에 미생물제제 혼합급여시 사료섭취량과 음수량을 증가시키는데 효과가 있는 것으로 조사되었으나, 비료성분 배설량에는 큰 차이를 보이지 않는 것으로 조사되었으나, BOD 등 오염물질농도의 경우에는 미생물제제 A급여구에서 가장 낮게 조사되어 비육돈사료에 미생물제제 급여시 오염물질 저감효과가 있는 것으로 조사되었다. Study for the effect of three different microbial feed additives(henceforth MA-A, MA-B, and MA-C) on feed coversion rate, and physical and chemical characteristics of swine finisher was conducted. MA-B had higher number of Lactobacillus spp. and yeast, compared to any other. The amylase activity of MA-B was also higher than any other. The daily feed intake rates of pigs fed control, MA-A, MA-B and MA-C were 3.15, 3.14, 3.31 and 3.42 kg, respectively. MA-C had the highest weight gain. However, there was no significant difference between treatments. The weights of feces daily excreted by pigs fed control, MA-A, MA-B, and MA-C were 2.14, 2.02, 2.18, and 2.23 kg/day, respectively. The volume of urine daily excreted by pigs fed control, MA-A, MA-B, and MA-C were 3.14, 3.26, 3.27, and $3.41\;{\ell}/day$, respectively. Water content, T-N, $P_{2}O_{5}$, and $K_{2}O$ in swine manure were not significantly different between treatments. The BOD were between 42,576 and $67,450\;mg/{\ell}$ for feces and were between 5,882.5 and $8,657.5\;mg/{\ell}$ for urine, respectively. The SS were between 138,000 and $180,000\;mg/{\ell}$ for feces and were between 875.0 and $1450.0mg/{\ell}$ for urine, respectively.

Forward-backward asymmetry of top quark in unparticle physics

Chen, C.H.,Cvetic, G.,Kim, C.S. North-Holland Pub. Co 2011 Physics letters: B Vol.694 No.4

The updated CDF measurement of the forward-backward asymmetry A<SUB>FB</SUB> in the top quark production pp@?→tt@? at Tevatron (with s=1.96 TeV) shows a deviation of 2σ from the value predicted by the Standard QCD Model. We present calculation of this quantity in the scenario, where colored unparticle physics contributes to the s-channel of the process, and obtain the regions in the plane of the unparticle parameters λ and d<SUB>U</SUB>, which give the values of the A<SUB>FB</SUB> and of the total tt@? production cross section compatible with the present measurements.

Integrated cladding-pumped multicore few-mode erbium-doped fibre amplifier for space-division-multiplexed communications

Chen, H.,Jin, C.,Huang, B.,Fontaine, N. K.,Ryf, R.,Shang, K.,Gré,goire, N.,Morency, S.,Essiambre, R.-J.,Li, G.,Messaddeq, Y.,LaRochelle, S. Nature Publishing Group 2016 Nature photonics Vol.10 No.8

Space-division multiplexing (SDM), whereby multiple spatial channels in multimode and multicore optical fibres are used to increase the total transmission capacity per fibre, is being investigated to avert a data capacity crunch and reduce the cost per transmitted bit. With the number of channels employed in SDM transmission experiments continuing to rise, there is a requirement for integrated SDM components that are scalable. Here, we demonstrate a cladding-pumped SDM erbium-doped fibre amplifier (EDFA) that consists of six uncoupled multimode erbium-doped cores. Each core supports three spatial modes, which enables the EDFA to amplify a total of 18 spatial channels (six cores × three modes) simultaneously with a single pump diode and a complexity similar to a single-mode EDFA. The amplifier delivers >20 dBm total output power per core and <7 dB noise figure over the C-band. This cladding-pumped EDFA enables combined space-division and wavelength-division multiplexed transmission over multiple multimode fibre spans.

Investigation of _Bu,d→(π,K)π decays within unparticle physics

Chen, Chuan-Hung,Kim, C.S.,Yoon, Yeo Woong Elsevier 2009 Physics letters: B Vol.671 No.2

<P><B>Abstract</B></P><P>We investigate the implication of unparticle physics on the <SUB>Bu,d</SUB>→(π,K)π decays under the constraints of the <SUB>Bd,s</SUB>–<SUB>B¯d,s</SUB> mixing. We found that not only the unparticle parameters that belong to the flavor changing neutral current (FCNC) processes but also scaling dimension <SUB>dU</SUB> could be constrained by the <SUB>Bd,s</SUB>–<SUB>B¯d,s</SUB> mixing phenomenology. Employing the minimum <SUP>χ2</SUP> analysis to the <SUB>Bu,d</SUB>→(π,K)π decays with the constraints of <SUB>Bd,s</SUB> mixing, we find that the puzzle of large branching ratio for <SUB>Bd</SUB>→<SUP>π0</SUP><SUP>π0</SUP> and the discrepancy between the standard model estimation and data for the direct CP asymmetry of <SUP>B+</SUP>→<SUP>K+</SUP><SUP>π0</SUP> and <SUB>Bd</SUB>→<SUP>π+</SUP><SUP>π−</SUP> can be resolved well. However, the mixing induced CP asymmetry of <SUB>Bd</SUB>→<SUB>KS</SUB><SUP>π0</SUP> could not be well accommodated by the unparticle contributions.</P>

c-Cbl-Mediated Neddylation Antagonizes Ubiquitination and Degradation of the TGF-β Type II Receptor

Zuo, W.,Huang, F.,Chiang, Y.,Li, M.,Du, J.,Ding, Y.,Zhang, T.,Lee, H.,Jeong, L.,Chen, Y.,Deng, H.,Feng, X.H.,Luo, S.,Gao, C.,Chen, Y.G. Cell Press 2013 Molecular cell Vol.49 No.3

Transforming growth factor β (TGF-β) is a potent antiproliferative factor in multiple types of cells. Deregulation of TGF-β signaling is associated with the development of many cancers, including leukemia, though the molecular mechanisms are largely unclear. Here, we show that Casitas B-lineage lymphoma (c-Cbl), a known proto-oncogene encoding an ubiquitin E3 ligase, promotes TGF-β signaling by neddylating and stabilizing the type II receptor (TβRII). Knockout of c-Cbl decreases the TβRII protein level and desensitizes hematopoietic stem or progenitor cells to TGF-β stimulation, while c-Cbl overexpression stabilizes TβRII and sensitizes leukemia cells to TGF-β. c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to TβRII at Lys556 and Lys567. Neddylation of TβRII promotes its endocytosis to EEA1-positive early endosomes while preventing its endocytosis to caveolin-positive compartments, therefore inhibiting TβRII ubiquitination and degradation. We have also identified a neddylation-activity-defective c-Cbl mutation from leukemia patients, implying a link between aberrant TβRII neddylation and leukemia development.

Valorization of lignocellulosic fibres of paper waste into levulinic acid using solid and aqueous Brønsted acid

Chen, Season S.,Wang, Lei,Yu, Iris K.M.,Tsang, Daniel C.W.,Hunt, Andrew J.,Jé,rô,me, Franç,ois,Zhang, Shicheng,Ok, Yong Sik,Poon, Chi Sun Elsevier 2018 Bioresource technology Vol.247 No.-

<P><B>Abstract</B></P> <P>This study aims to produce levulinic acid (LA) from paper towel waste in environment-friendly and economically feasible conditions, and evaluate the difference using solid and aqueous Brønsted acids. Direct dehydration of glucose to LA required sufficiently strong Brønsted acidity, where Amberlyst 36 demonstrated rapid production of approximately 30Cmol% of LA in 20min. However, the maximum yield of LA was limited by mass transfer. In contrast, the yield of LA gradually increased to over 40Cmol% in 1M H<SUB>2</SUB>SO<SUB>4</SUB> at 150°C in 60min. The SEM images revealed the conversion in dilute acids under microwave at 150°C resulting in swelling structures of cellulose, which were similar to the pre-treatment process with concentrated acids. Further increase in reaction temperature to 200°C significantly shortened the reaction time from 60 to 2.5min, which saved the energy cost as revealed in preliminary cost analysis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 30% of levulinic acid (LA) yielded from paper towel over Amberlyst 36 in 20min. </LI> <LI> Maximum yield of LA was comparable using dilute sulphuric acid at 150 and 200°C. </LI> <LI> Cellulose underwent swelling in dilute acid with microwave heating at 150°C. </LI> <LI> Conversion at 200°C shortened reaction time and reduced total energy consumption. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Janus activated kinase 2/signal transducer and activator of transcription 3 pathway mediates icariside II-induced apoptosis in U266 multiple myeloma cells

Kim, S.H.,Ahn, K.S.,Jeong, S.J.,Kwon, T.R.,Jung, J.H.,Yun, S.M.,Han, I.,Lee, S.G.,Kim, D.K.,Kang, M.,Chen, C.Y.,Lee, J.W.,Kim, S.H. North-Holland ; Elsevier Science Ltd 2011 european journal of pharmacology Vol.654 No.1

Although the flavonoid icariside II exhibits anti-inflammatory and anti-cancer activities, its molecular targets/pathways in human multiple myeloma cells are poorly understood. To analyze the effects on signal transducer and activator of transcription 3 (STAT3) signaling and apoptosis, U266 multiple myeloma cells were treated with icariside II and performed Western blotting, electrophoretic mobility gel shift assay (EMSA), RT-PCR, proliferation assay, cell cycle analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Icariside II inhibited STAT3 activation and enhanced the expression of SHP-1 and PTEN through inhibiting Janus activated kinase 2 (JAK2) and c-Src. Icariside II down-regulated the expression of STAT3 target genes Bcl-2, Bcl-x<SUB>L</SUB>, survivin, cyclin D<SUB>1</SUB>, COX-2 and vascular endothelial growth factor (VEGF). Also, icariside II enhanced poly (ADP-ribose) polymerase (PARP) cleavage and caspase-3 activation. Pervanadate reversed the icariside II-mediated STAT3 inactivation and also blocked the cleavages of caspase-3 and PARP, suggesting involvement of STAT3 pathway in icariside II-induced apoptosis. Furthermore, icariside II enhanced the apoptotic effects of clinically used drugs thalidomide and bortezomib in U266 cells. Icariside II could be a potential therapeutic intervention agent alone or in combination with current drugs for multiple myeloma as a novel blocker of STAT3 signaling cascades at multiple levels, contributing to its anti-proliferative and anti-apoptosis.

Two S-wave gap symmetry for single crystals of the superconductor BaFe_1.8Co_0.2As₂

Choi, K.Y.,Kim, S.H.,Choi, C.,Jung, M.H.,Wang, X.F.,Chen, X.H.,Noh, J.D.,Lee, S.I. North-Holland 2010 Physica. C, Superconductivity Vol.470 No.suppl1

To clarify the gap structure of the iron-pnictide superconductors, we synthesized optimally doped single crystals of BaFe<SUB>1.8</SUB>Co<SUB>0.2</SUB>As<SUB>2</SUB>, which had a critical temperature, T<SUB>c</SUB>, of 23.6K. The initial M-H curve was used to find the lower critical field, H<SUB>c1</SUB>. The full range of the temperature dependence of H<SUB>c1</SUB> was explained by using a two S-wave gap symmetry. We estimate the two gap as Δ<SUB>1</SUB>(0)=1.64+/-0.2meV for the small gap and Δ<SUB>2</SUB>(0)=6.20+/-0.2meV for the large gap.