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Kim, Minsuk,Sang Yi, Jeong,Kim, Joonwon,Kim, Ji-Nu,Kim, Min Woo,Kim, Byung-Gee Wiley 2014 Biotechnology journal Vol.9 No.9
<P>Streptomycetes are industrially and pharmaceutically important bacteria that produce a variety of secondary metabolites including antibiotics. Streptomycetes have a complex metabolic network responsible for the production of secondary metabolites and the utilization of organic residues present in soil. In this study, we reconstructed a high-quality metabolic model for Streptomyces coelicolor A3(2), designated iMK1208, in order to understand and engineer the metabolism of this model species. In comparison to iIB711, the previous metabolic model for S. coelicolor, the predictive power of iMK1208 was enhanced by the recent insights that enabled the incorporation of an updated biomass equation, stoichiometric matrix, and energetic parameters. iMK1208 was validated by comparing predictions with the experimental data for growth capability in various growth media. Furthermore, we applied a strain-design algorithm, flux scanning based on enforced objective flux (FSEOF), to iMK1208 for actinorhodin overproduction. FSEOF results identified not only previously known gene overexpression targets such as actII-ORF4 and acetyl-CoA carboxylase, but also novel targets such as branched-chain α-keto acid dehydrogenase (BCDH). We constructed and evaluated the BCDH overexpression mutant, which showed a 52-fold increase in actinorhodin production, validating the prediction power of iMK1208. Hence iMK1208 was shown to be a useful and valuable framework for studying the biotechnologically important Streptomyces species using the principles of systems biology and metabolic engineering.</P>
Kim, Joonwon,Yoo, Hee-Wang,Kim, Minsuk,Kim, Eun-Jung,Sung, Changmin,Lee, Pyung-Gang,Park, Beom Gi,Kim, Byung-Gee Elsevier 2018 Metabolic engineering Vol.47 No.-
<P><B>Abstract</B></P> <P>ω-Hydroxy palmitic acid (ω-HPA) is a valuable compound for an ingredient of artificially synthesized ceramides and an additive for lubricants and adhesives. Production of such a fatty acid derivative is limited by chemical catalysis, but plausible by biocatalysis. However, its low productivity issue, including formations of unsaturated fatty acid (UFA) byproducts in host cells, remains as a hurdle toward industrial biological processes. In this study, to achieve selective and high-level production of ω-HPA from glucose in <I>Escherichia coli</I>, FadR, a native transcriptional regulator of fatty acid metabolism, and its regulon were engineered. First, FadR was co-expressed with a thioesterase with a specificity toward palmitic acid production to enhance palmitic acid production yield, but a considerable quantity of UFAs was also produced. In order to avoid the UFA production caused by <I>fadR</I> overexpression, FadR regulon was rewired by i) mutating FadR consensus binding sites of <I>fabA</I> or <I>fabB</I>, ii) integrating <I>fabZ</I> into <I>fabI</I> operon, and iii) enhancing the strength of <I>fabI</I> promoter. This approach led to dramatic increases in both proportion (48.3–83.0%) and titer (377.8 mg/L to 675.8 mg/L) of palmitic acid, mainly due to the decrease in UFA synthesis. Introducing a fatty acid ω-hydroxylase, CYP153A35, into the engineered strain resulted in a highly selective production of ω-HPA (83.5 mg/L) accounting for 87.5% of total ω-hydroxy fatty acids. Furthermore, strategies, such as i) enhancement in CYP153A35 activity, ii) expression of a fatty acid transporter, iii) supplementation of triton X-100, and iv) separation of the ω-HPA synthetic pathway into two strains for a co-culture system, were applied and resulted in 401.0 mg/L of ω-HPA production. For such selective productions of palmitic acid and ω-HPA, the rewiring of FadR regulation in <I>E. coli</I> is a promising strategy to develop an industrial process with economical downstream processing.</P> <P><B>Highlights</B></P> <P> <UL> <LI> FadR regulon was rewired by mutating FadR binding sites of promoters. </LI> <LI> Rewiring FadR regulation decreased the degree of unsaturation from 33.4% to 5.9% in free fatty acid profile. </LI> <LI> Co-culture system enhanced productivity by relieving the possible metabolic burden. </LI> <LI> In total, 401.0 mg/L of ω-hydroxy palmitic acid was produced in high percentages. </LI> </UL> </P>
Steep switching characteristics of single-gated feedback field-effect transistors
Kim, Minsuk,Kim, Yoonjoong,Lim, Doohyeok,Woo, Sola,Cho, Kyoungah,Kim, Sangsig IOP Pub 2017 Nanotechnology Vol.28 No.5
<P>In this study, we propose newly designed feedback field-effect transistors that utilize the?positive feedback of charge carriers in single-gated silicon channels to achieve steep switching behaviors. The band diagram, <I>I–V</I> characteristics, subthreshold swing, and on/off current ratio are analyzed using a commercial device simulator. Our proposed feedback field-effect transistors exhibit subthreshold swings of less than 0.1 mV dec<SUP>−1</SUP>, an on/off current ratio of approximately 10<SUP>11</SUP>, and an on-current of approximately 10<SUP>−4</SUP> A at room temperature, demonstrating that the switching characteristics are superior to those?of other silicon-based devices. In addition, the device parameters that affect the device performance, hysteresis characteristics, and temperature-dependent device characteristics are discussed in detail.</P>
Minsuk Kim,Youngin Jeon,Yoonjoong Kim,Sangsig Kim IEEE 2015 IEEE TRANSACTIONS ON NANOTECHNOLOGY Vol. No.
<P>Dual-functional devices based on gated p-i-n diodes are proposed in this simulation study. The dual-functional devices function not only as n-channel tunneling field-effect transistors (nTFETs) but also as p-channel impact-ionization FETs (p-IFETs), depending on the bias conditions. In this study, the I-V characteristics, subthreshold swing (SS), ON/OFF current ratio (I<SUB>on</SUB>/I<SUB>off</SUB>), and band diagram are analyzed using a device simulator (Silvaco Atlas), and the features of the n-TFETs and the p-IFETs are extracted from the simulated data. The n-TFETs exhibit high I<SUB>on</SUB>/I<SUB>off</SUB> of ~10<SUP>11</SUP> and a sub-60-mV/dec SS, and the p-IFETs yield extremely low SS of as small as 8.57 mV/dec. Our approach is one of the useful methods to design multifunctional electronics for lowering the power consumption.</P>
Impact ionization and tunneling operations in charge-plasma dopingless device
Kim, Minsuk,Kim, Yoonjoong,Lim, Doohyeok,Woo, Sola,Im, Kyeungmin,Cho, Jinsun,Kang, Hyungu,Kim, Sangsig Elsevier 2017 Superlattices and microstructures Vol.111 No.-
<P><B>Abstract</B></P> <P>In this paper, we present the impact ionization and tunneling operations in a newly designed dopingless device. Our proposed device functions selectively—as either a <I>p</I>-channel impact-ionization MOSFET (<I>p</I>-IMOS) or an <I>n</I>-channel tunneling field-effect transistor (<I>n</I>-TFET)—according to the bias conditions. To realize the dopingless device, the charge-plasma effect is employed to induce <I>n</I>- or <I>p</I>-type regions without any doping process, by choosing an electrode metal with an appropriate work function. The band diagrams, <I>I–V</I> characteristics, subthreshold swings (<I>SS</I>), and carrier-concentration profiles of the device under the <I>p</I>-IMOS and <I>n</I>-TFET operation modes are analyzed in our study, using a commercial device simulator. The device yields an extremely low <I>SS</I> of 0.53 mV/dec under the <I>p</I>-IMOS operation mode. It also exhibits a low off-current of approximately 10<SUP>−14</SUP> A/μm and a high <I>I</I> <SUB>ON</SUB>/<I>I</I> <SUB>OFF</SUB> of approximately 10<SUP>8</SUP>, under the <I>n</I>-TFET operation mode.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A charge-plasma effect is employed to realize our newly designed dopingless device. </LI> <LI> The single dopingless device possesses both <I>p</I>-IMOS and <I>n</I>-TFET characteristics. </LI> <LI> Without any doping, the device can act similar to a conventional doped device. </LI> </UL> </P>
Exploiting transcriptomic data for metabolic engineering: toward a systematic strain design
Kim, Minsuk,Park, Beom Gi,Kim, Joonwon,Kim, Jin Young,Kim, Byung-Gee Elsevier 2018 Current opinion in biotechnology Vol.54 No.-
<P>Transcriptomics is now recognized as a primary tool for metabolic engineering as it can be used for identifying new strain designs by diagnosing current states of microbial cells. This review summarizes current application of transcriptomic data for strain design. Along with a few successful examples, limitations of conventionally used differentially expressed gene-based strain design approaches have been discussed, which have been major reasons why transcriptomic data are considerably underutilized. Recently, integrative network-based approaches interpreting transcriptomic data in the context of biological networks were invented to provide complimentary solutions for metabolic engineering by overcoming the limitations of conventional approaches. Here, we highlight recent pioneering studies in which integrative network-based methods have been used for providing novel strain designs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Transcriptomic data can facilitate strain design but yet underutilized. </LI> <LI> Differentially expressed genes have been primary targets for metabolic engineering. </LI> <LI> Integrative network-based analysis of transcriptomic data could provide novel strain design. </LI> <LI> More computational tools are needed to fully exploit transcriptomic data for strain design. </LI> </UL> </P>