Production of ω-hydroxy palmitic acid using CYP153A and comparison of cytochrome P450 electron transfer system in vivo

EunOk JUNG,Beom-gi PARK,Hee-Wang YOO,Byung-Gee KIM 한국생물공학회 2016 한국생물공학회 학술대회 Vol.2016 No.4

Optimal Control Theory Applied to a Difference Equation Model of Cardiopulmonary Resuscitation with Chest Compression Only

Eunok Jung,Suzanne Lenhart,Vladimir Protopopescu,Charles F Babbs 한국산업응용수학회 2005 한국산업응용수학회 학술대회 논문집 Vol.- No.-

Each year, more than 250,000 people die from cardiac arrest in the USA alone. Despite widespread use of cardiopulmonary resuscitation (CPR), the number of patients surviving from cardiac arrest remains low. Indeed, the rate of survival for CPR performed out of the hospital is 3%, while for patients who undergo cardiac arrest in the hospital, the rate of survival is 10-15%. One of the reasons for this situation is that the practical technique of CPR has changed little since the 1960's. The standard and various alternative CPR techniques such as interposed abdominal compression, active compression-decompression, and Lifestick CPR have been represented in various mathematical models [1, 2, 3]. Here, we illustrate our approach on a model of standard CPR, performed manually or by a mechanical device. The goal of this research is to reconsider the traditional CPR technique and to suggest novel strategies for improving it, by using the optimal control methodology. The techniques of optimal control are applied to a validated blood circulation model of cardiopulmonary resuscitation (CPR) by Babbs [1]. In his model, heart and blood vessels are represented as a network of resistance and compliances. Pressures in the chest and in the vascular compliances are computed from difference equations. Blood flows are computed form Ohm's law, accounting for the action of one-way valves in the heart. The circulation model describes the adult human circulation (hemodynamics) and consists of seven difference equations, with time as the discrete underlying variable. As a control input, we choose the pattern of the pressure within the chest. More precisely, this control is actually the forcing pressure developed inside the chest as a result of external compression or decompression by the rescuer. The optimum waveform of this forcing pressure as a function of time was determined from control theory. The optimum waveform maximized systemic perfusion pressure (SPP) between the thoracic aorta and the superior vena cava over a period of 13.3 sec of continuous chest compression. The new aspect in this application is that the control values from the two previous time steps are used to calculate the pressures (state variables) at the current time step. We prove the existence and uniqueness of the optimal control and provide a new CPR strategy, with increased blood flow. The characterization of the optimal control is given in terms of the solutions of the circulation model and of the corresponding adjoint system. The numerical results show a significant increase in the blood flow as compared with standard CPR. We applied optimal control theory to the problem of CPR without any preconceived notions about what the results should be. The fact that optimal control theory found a solution incorporating two strategies already discovered in animal experiments and clinical trials, namely HIC-CPR with high impulse compressions, and ACD-CPR with active compression and decompression of the chest is quite interesting, since no bias toward these particular solutions was included in the problem definition or in the mathematics. The results of this first-ever application of optimal control theory to CPR are interesting-perhaps less so in the exact numerical values of the solution than in the strategy they imply namely the combination of high impulse chest compression with intermittent decompression, as well as the idea that the ratio of compressions to decompressions need not necessarily be 1:1. The high impulse compressions augment forward flow and the active decompressions increase venous return to the pump. Such strategies can be realistically implemented by human rescuers or by non-fatiguing mechanical devices.

Improving ω-Hydroxylation Activity of CYP153 toward Hexadecanoic Acid by Rational Enzyme Design

EunOk JUNG,Beom-gi PARK,Hee-Wang YOO,Byung-Gee KIM 한국생물공학회 2015 한국생물공학회 학술대회 Vol.2015 No.10

THE INFLUENCE OF DRIVING FUNCTION ON FLOW DRIVEN BY PUMPING WITHOUT VALVES

EUNOK JUNG 한국산업응용수학회 2011 Journal of the Korean Society for Industrial and A Vol.15 No.2

Auid dynamics driven by pumping without valves (valveless pumping) shows interesting physics. Especially, the driving function to generate valveless pump mechanism is one of important factors. We consider a closed system of valveless pump which consists of flexible tube part and stiffer part. Fluid and structure (elastic tube) interaction motions are generated by the periodic compress-and-release actions on an asymmetric location of the elastic loop of tubing. In this work, we demonstrate how important the driving forcing function affects a net flow in the valveless circulatory system and investigate which parameter set of the system gives a more efficient net flow around the loop.

Bioconversion of p-coumaric acid to p-hydroxystyrene using phenolic acid decarboxylase from B. amyloliquefaciens in biphasic reaction system

Jung, Da-Hye,Choi, Wonji,Choi, Kwon-Young,Jung, Eunok,Yun, Hyungdon,Kazlauskas, Romas J.,Kim, Byung-Gee Springer-Verlag 2013 Applied microbiology and biotechnology Vol.97 No.4

<P>Phenolic acid decarboxylase (PAD) catalyzes the non-oxidative decarboxylation of p-coumaric acid (pCA) to p-hydroxystyrene (pHS). PAD from Bacillus amyloliquefaciens (BAPAD), which showed k (cat)/K (m) value for pCA (9.3 x 10(3) mM(-1) s(-1)), was found as the most active one using the 'Subgrouping Automata' program and by comparing enzyme activity. However, the production of pHS of recombinant Escherichia coli harboring BAPAD showed only a 22.7 % conversion yield due to product inhibition. Based on the partition coefficient of pHS and biocompatibility of the cell, 1-octanol was selected for the biphasic reaction. The conversion yield increased up to 98.0 % and 0.83 g/h/g DCW productivity was achieved at 100 mM pCA using equal volume of 1-octanol as an organic solvent. In the optimized biphasic reactor, using a three volume ratio of 1-octanol to phosphate buffer phase (50 mM, pH 7.0), the recombinant E. coli produced pHS with a 88.7 % conversion yield and 1.34 g/h/g DCW productivity at 300 mM pCA.</P>

MULTIDIMENSIONAL OPEN SYSTEM FOR VALVELESS PUMPING

JUNG, EUNOK,KIM, DO WAN,LEE, JONGGUL,LEE, WANHO Korean Mathematical Society 2015 대한수학회보 Vol.52 No.6

In this study, we present a multidimensional open system for valveless pumping (VP). This system consists of an elastic tube connected to two open tanks filled with a fluid under gravity. The two-dimensional elastic tube model is constructed based on the immersed boundary method, and the tank model is governed by a system of ordinary differential equations based on the work-energy principle. The flows into and out of the elastic tube are modeled in terms of the source/sink patches inside the tube. The fluid dynamics of this system is generated by the periodic compress-and-release action applied to an asymmetric region of the elastic tube. We have developed an algorithm to couple these partial differential equations and ordinary differential equations using the pressure-flow relationship and the linearity of the discretized Navier-Stokes equations. We have observed the most important feature of VP, namely, the existence of a unidirectional net flow in the system. Our computations are focused on the factors that strongly influence the occurrence of unidirectional flows, for example, the frequency, compression duration, and location of pumping. Based on these investigations, some case studies are performed to observe the details of the ow features.

Optimal treatment strategies of Tuberculosis in South Korea

Eunok Jung,Sungim Whang,Sunwha Choi 한국산업응용수학회 2010 한국산업응용수학회 학술대회 논문집 Vol.5 No.1

We have developed a tuberculosis (TB) model in South Korea using the SEIR model with the time-dependent parameters. South Korea ranked the highest TB incidence among members of the Organization for Economic Cooperation and Development (OECD) in 2004. The observed data from the Korea Center for Disease Control and Prevention (KCDC) shows a certain rise of the incidence people after 2001 yr because of increasing foreign workers with active-TB and starting the operation of the Korean Tuberculosis Surveillance System. The least-square curve fitting has been used for fitting the parameters in our model to the observed data. In this work, we also propose the optimal treatment strategies of TB model in South Korea using optimal control theory based on our TB model from 2001 yr to 2008 yr.

Semi-rational engineering of CYP153A35 to enhance ω-hydroxylation activity toward palmitic acid

Jung, Eunok,Park, Beom Gi,Yoo, Hee-Wang,Kim, Joonwon,Choi, Kwon-Young,Kim, Byung-Gee Springer-Verlag 2018 Applied Microbiology and Biotechnology Vol.102 No.1

<P>CYP153A35 from Gordonia alkanivorans was recently characterized as fatty acid omega-hydroxylase. To enhance the catalytic activity of CYP153A35 toward palmitic acid, site-directed saturation mutagenesis was attempted using a semi-rational approach that combined structure-based computational analysis and subsequent saturation mutagenesis. Using colorimetric high-throughput screening (HTS) method based on O-demethylation activity of P450, CYP153A35 D131S and D131F mutants were selected. The best mutant, D131S, having a single mutation on BC-loop, showed 13- and 17-fold improvement in total turnover number (TTN) and catalytic efficiency (k (cat)/K (M)) toward palmitic acid compared to wild-type, respectively. However, in whole-cell reaction, D131S mutant showed only 50% improvement in omega-hydroxylated palmitic acid yield compared to the wild type. Docking simulation studies explained that the effect of D131S mutation on the catalytic activity would be mainly caused by the binding pose of fatty acids in the substrate access tunnel of the enzyme. This effect of D131S mutation on the catalytic activity is synergistic with that of the mutations in the active site previously reported.</P>

What is optimal cardiopulmonary resuscitation technique for children?

Eunok Jung 한국산업응용수학회 2011 한국산업응용수학회 학술대회 논문집 Vol.6 No.1

We present optimal cardiopulmonary resuscitation (CPR) technique based on body weight using optimal control theory. The validated blood circulation model of CPR has been modified for various body weights by the scaling law. The external chest and abdomen pressures are chosen as controls and the goal is to maximize the mean systemic perfusion pressure (SPP). The numerical results show that four phases CPR method, such as Lifestick CPR, gives the optimal CPR technique. The most interesting result is that more weighted person needs longer compression duration on the abdomen and less weighted person, like children, needs longer compression duration on the chest.

Characterization of two CYP153s from Bacteria and production of ω-hydroxy fatty acids

Eunok JUNG,MD.Murshidul AHSAN,Beom Gi PARK,Hyungdon YUN,Byung-Gee KIM 한국생물공학회 2014 한국생물공학회 학술대회 Vol.2014 No.4