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Gleason scores in prostate needle biopsy and prostatectomy specimens in prostatic adenocarcinoma: A correlation study

Awang A, Md Isa N, Yunus R, Azhar Shah S, Md Pauzi SH

Malays J Pathol, 2019 Dec;41(3):253-257.
PMID: 31901909

INTRODUCTION: Gleason scoring (GS) categorised prostatic adenocarcinoma into five prognostic grade groups (PGGs); associated with different prognosis and treatment. This study aims to correlate between Gleason scores of needle biopsies with the corresponding total prostatectomy specimens, and to assess the relationship between the percentage of Gleason 4 tumour pattern (GP4) within Gleason score 7 (GS7) needle biopsy groups with the pathological staging.
MATERIALS AND METHODS: Seventy-eight specimens of needle prostate biopsy and its subsequent radical prostatectomy were retrospectively studied. The GSs of the needle biopsy were compared with the corresponding prostatectomy specimens. The percentage of GP4 in GS7 needle biopsy groups was calculated and correlated with the pathological staging.
RESULTS: More than half (60%) of GS 6 needle biopsy cases (PGG 1) were upgraded in the prostatectomy specimen, while the majority (80%) of the GS7 needle biopsy groups (PGG 2 and 3) remain unchanged. Cohen's Kappa shows fair agreement in the Gleason scoring between needle biopsies and prostatectomy specimens, K = 0.324 (95% CI, 6.94 to 7.29), p <0.0005 and in the percentage of GP4 in GS7 needle biopsy groups and their corresponding radical prostatectomy specimens, K = 0.399 (95% CI 34.2 - 49.2), p<0.0005. A significant relationship was seen between the percentage of GP4 in GS7 needle biopsy with the pT and pN stage of its radical prostatectomy (p = 0.008 and p=0.001 respectively).
CONCLUSION: A higher percentage of GP4 in GS7 tumour is associated with worse tumour behaviour, therefore it is crucial for clinicians to realise this in deciding the optimal treatment.
Fulltext Virulence and Antimicrobial Resistance Profiles of Salmonella enterica Serovars Isolated from Chicken at Wet Markets in Dhaka, Bangladesh

Siddiky NA, Sarker MS, Khan MSR, Begum R, Kabir ME, Karim MR, et al.

Microorganisms, 2021 Apr 28;9(5).
PMID: 33924919 DOI: 10.3390/microorganisms9050952

Virulent and multi drug resistant (MDR) Salmonellaenterica is a foremost cause of foodborne diseases and had serious public health concern globally. The present study was undertaken to identify the pathogenicity and antimicrobial resistance (AMR) profiles of Salmonellaenterica serovars recovered from chicken at wet markets in Dhaka, Bangladesh. A total of 870 cecal contents of broiler, sonali, and native chickens were collected from 29 wet markets. The overall prevalence of S. Typhimurium, S. Enteritidis, and untyped Salmonella spp., were found to be 3.67%, 0.57%, and 1.95% respectively. All isolates were screened by polymerase chain reaction (PCR) for eight virulence genes, namely invA, agfA, IpfA, hilA, sivH, sefA, sopE, and spvC. S. Enteritidis isolates carried all virulence genes whilst S. Typhimurium isolates carried six virulence genes except sefA and spvC. A diverse phenotypic and genotypic AMR pattern was found. Harmonic descending trends of resistance patterns were observed among the broiler, sonali, and native chickens. Interestingly, virulent and MDR Salmonella enterica serovars were found in native chicken, although antimicrobials were not used in their production cycle. The research findings anticipate that virulent and MDR Salmonella enterica are roaming in the wet markets which can easily anchor to the vendor, consumers, and in the food chain.
Fulltext Exploring barriers to accessing healthcare services for older indigenous people in the Chittagong Hill Tract, Bangladesh

Hossen MS, Sohel MS, Horaira GA, Laskor MAH, Sumi ABA, Chowdhury S, et al.

AIMS Public Health, 2023;10(3):678-697.
PMID: 37842279 DOI: 10.3934/publichealth.2023047

We aim to investigate the obstacles faced by elderly indigenous individuals in the Chittagong Hill Tracts, Bangladesh when accessing healthcare services. A qualitative research approach was utilized, and data collection was carried out in three distinct regions of the aforementioned area. A total of 30 in-depth, semi-structured interviews and participant observations were conducted to achieve the research objectives. Thematic analysis utilizing both a deductive and inductive approach was employed to analyze the data. The Granheim method and Nvivo-12 software were utilized to process, analyze and code the data. The study's findings indicate that a lack of knowledge about healthcare needs, geographical barriers, poor financial conditions, higher cost of medical services, scarcity of hospitals nearby and communication barriers all contribute to inadequate access to healthcare services. By recognizing the factors that impede access to healthcare services in this region, this study offers valuable insight for policymakers and healthcare providers on how to enhance healthcare services for the indigenous population, especially the elderly. Furthermore, the government can adopt a more efficient approach to include these elderly individuals in various social safety net programs.
Fulltext Fine-scale population structure and ecotypes of anadromous Hilsa shad (Tenualosa ilisha) across complex aquatic ecosystems revealed by NextRAD genotyping

Asaduzzaman M, Wahab MA, Rahman MJ, Nahiduzzzaman M, Dickson MW, Igarashi Y, et al.

Sci Rep, 2019 11 05;9(1):16050.
PMID: 31690767 DOI: 10.1038/s41598-019-52465-2

The anadromous Hilsa shad (Tenualosa ilisha) live in the Bay of Bengal and migrate to the estuaries and freshwater rivers for spawning and nursing of the juveniles. This has led to two pertinent questions: (i) do all Hilsa shad that migrate from marine to freshwater rivers come from the same population? and (ii) is there any relationship between adults and juveniles of a particular habitat? To address these questions, NextRAD sequencing was applied to genotype 31,276 single nucleotide polymorphism (SNP) loci for 180 individuals collected from six strategic locations of riverine, estuarine and marine habitats. FST OutFLANK approach identified 14,815 SNP loci as putatively neutral and 79 SNP loci as putatively adaptive. We observed that divergent local adaptations in differing environmental habitats have divided Hilsa shad into three genetically structured ecotypes: turbid freshwater (Western Riverine), clear freshwater (Eastern Riverine) and brackish-saline (Southern Estuarine-Marine). Our results also revealed that genes involved in neuronal activity may have facilitated the juveniles' Hilsa shad in returning to their respective natal rivers for spawning. This study emphasized the application of fundamental population genomics information in strategizing conservation and management of anadromous fish such as Hilsa shad that intersect diverse ecotypes during their life-history stages.
Antioxidant, anti-inflammatory and synergistic anti-hyperglycemic effects of Malaysian propolis and metformin in streptozotocin-induced diabetic rats

Nna VU, Abu Bakar AB, Md Lazin MRML, Mohamed M

Food Chem Toxicol, 2018 Oct;120:305-320.
PMID: 30026088 DOI: 10.1016/j.fct.2018.07.028

Diabetes mellitus is characterized by hyperglycemia which causes oxidative stress. Propolis has been reported to have antihyperglycemic and antioxidant potentials. The present study therefore examined the anti-hyperglycemic, antioxidant and anti-inflammatory activities of Malaysian propolis (MP) using streptozotocin-induced diabetic rats. Ethanol extract of MP showed in vitro antioxidant (DPPH, FRAP and H2O2 radical scavenging) and α-glucosidase inhibition activities. Male Sprague Dawley rats were either treated with distilled water (normal control and diabetic control), MP (300 mg/kg b. w.), metformin (Met) (300 mg/kg b. w.) or both. After four weeks, fasting blood glucose decreased, while body weight change and serum insulin level increased significantly in MP, Met and MP + Met treated diabetic groups compared to diabetic control (DC) group. Furthermore, pancreatic antioxidant enzymes, total antioxidant capacity, interleukin (IL)-10 and proliferating cell nuclear antigen increased, while malondialdehyde, nuclear factor-kappa B (p65), tumor necrosis factor alpha, IL-1β and cleaved caspase-3 decreased significantly in the treated diabetic groups compared to DC group. Histopathology of the pancreas showed increased islet area and number of beta cells in the treated groups, compared to DC group, with D + MP + Met group comparable to normal control. We conclude that MP has anti-hyperglycemic, antioxidant, anti-inflammatory and antiapoptotic potentials, and exhibits synergistic effect with metformin.
Computational algorithmic and molecular dynamics study of functional and structural impacts of non-synonymous single nucleotide polymorphisms in human DHFR gene

Alam MS, Saleh MA, Mozibullah M, Riham AT, Solayman M, Gan SH

Comput Biol Chem, 2021 Dec;95:107587.
PMID: 34710812 DOI: 10.1016/j.compbiolchem.2021.107587

Human dihydrofolate reductase (DHFR) is a conserved enzyme that is central to folate metabolism and is widely targeted in pathogenic diseases as well as cancers. Although studies have reported the fact that genetic mutations in DHFR leads to a rare autosomal recessive inborn error of folate metabolism and drug resistance, there is a lack of an extensive study on how the deleterious non-synonymous SNPs (nsSNPs) disrupt its phenotypic effects. In this study, we aim at discovering the structural and functional consequences of nsSNPs in DHFR by employing a combined computational approach consisting of ten recently developed in silico tools for identification of damaging nsSNPs and molecular dynamics (MD) simulation for getting deeper insights into the magnitudes of damaging effects. Our study revealed the presence of 12 most deleterious nsSNPs affecting the native phenotypic effects, with three (R71T, G118D, Y122D) identified in the co-factor and ligand binding active sites. MD simulations also suggested that these three SNPs particularly Y122D, alter the overall structural flexibility and dynamics of the native DHFR protein which can provide more understandings into the crucial roles of these mutants in influencing the loss of DHFR function.
Fulltext A case of metastatic adenocarcinoma from an unknown primary involving the aortic bifurcation

Safri LS, Md Noh MSF, Hariz Ramli AR, Md Pauzi SH, Md Idris MA, Harunarashid H

J Vasc Surg Cases Innov Tech, 2018 Jun;4(2):160-162.
PMID: 29942910 DOI: 10.1016/j.jvscit.2018.03.004

Aortic malignant neoplasms are rare; these may be primary or secondary (metastatic). Increasing use of cross-sectional imaging has allowed better detection and diagnosis of these conditions. We encountered a young woman presenting with acute abdomen who was found on cross-sectional imaging to have a malignant tumor involving the aortic bifurcation. An en bloc excision of the tumor was performed, with distal aorta reconstruction using an aortoiliac Dacron graft; this was complicated with infection and graft occlusion, necessitating total removal and extra-anatomic bypass. A pathologic diagnosis of metastatic adenocarcinoma involving the aortic bifurcation, with an unknown primary, was made.
Fulltext Population Genomics of an Anadromous Hilsa Shad Tenualosa ilisha Species across Its Diverse Migratory Habitats: Discrimination by Fine-Scale Local Adaptation

Asaduzzaman M, Igarashi Y, Wahab MA, Nahiduzzaman M, Rahman MJ, Phillips MJ, et al.

Genes (Basel), 2019 12 30;11(1).
PMID: 31905942 DOI: 10.3390/genes11010046

The migration of anadromous fish in heterogenic environments unceasingly imposes a selective pressure that results in genetic variation for local adaptation. However, discrimination of anadromous fish populations by fine-scale local adaptation is challenging because of their high rate of gene flow, highly connected divergent population, and large population size. Recent advances in next-generation sequencing (NGS) have expanded the prospects of defining the weakly structured population of anadromous fish. Therefore, we used NGS-based restriction site-associated DNA (NextRAD) techniques on 300 individuals of an anadromous Hilsa shad (Tenualosa ilisha) species, collected from nine strategic habitats, across their diverse migratory habitats, which include sea, estuary, and different freshwater rivers. The NextRAD technique successfully identified 15,453 single nucleotide polymorphism (SNP) loci. Outlier tests using the FST OutFLANK and pcadapt approaches identified 74 and 449 SNPs (49 SNPs being common), respectively, as putative adaptive loci under a divergent selection process. Our results, based on the different cluster analyses of these putatively adaptive loci, suggested that local adaptation has divided the Hilsa shad population into two genetically structured clusters, in which marine and estuarine collection sites were dominated by individuals of one genetic cluster and different riverine collection sites were dominated by individuals of another genetic cluster. The phylogenetic analysis revealed that all the riverine populations of Hilsa shad were further subdivided into the north-western riverine (turbid freshwater) and the north-eastern riverine (clear freshwater) ecotypes. Among all of the putatively adaptive loci, only 36 loci were observed to be in the coding region, and the encoded genes might be associated with important biological functions related to the local adaptation of Hilsa shad. In summary, our study provides both neutral and adaptive contexts for the observed genetic divergence of Hilsa shad and, consequently, resolves the previous inconclusive findings on their population genetic structure across their diverse migratory habitats. Moreover, the study has clearly demonstrated that NextRAD sequencing is an innovative approach to explore how dispersal and local adaptation can shape genetic divergence of non-model anadromous fish that intersect diverse migratory habitats during their life-history stages.
Spatial distribution of heavy metal abundance at distance gradients of roadside agricultural soil from the busiest highway in Bangladesh: A multi-index integration approach

Islam MS, Nur-E-Alam M, Iqbal MA, Khan MB, Mamun SA, Miah MY, et al.

Environ Res, 2024 Feb 24.
PMID: 38408626 DOI: 10.1016/j.envres.2024.118551

Bangladesh is currently experiencing significant infrastructural development in road networking system through the construction or reconstruction of multiple roads and highways. Consequently, there is a rise in traffic intensity on roads and highways, along with a significant contamination of adjacent agricultural soils with heavy metals. The purpose of this study was to evaluate the ecological risk, health risk and the abundance of seven heavy metals (Cu, Mn, Pb, Cd, Cr, As, and Ni) in three distance gradients (0, 300, and 500 m) of agricultural soil along the Dhaka-Chattogram highway. The concentration of heavy metals was measured with an Atomic Absorption Spectrophotometer (AAS) on a total of 36 soil samples that were taken from 12 different sampling sites. Based on the findings, Cd had a high contamination factor for all distance gradients, whereas Cr had a moderate contamination factor in 67% of the study areas. According to the Pollution Load Index (PLI), Cd, Cr, and Pb were the predominant pollutants. Principal component analysis (PCA) result shows these metals mainly came from anthropogenic sources. The considerable positive correlations between Cu-Pb, Cu-Cd, Pb-Cd, and Cr-Ni all pointed to shared anthropogenic origins. As per Potential Ecological Risk Assessment (PERI) analysis, Pb, Cd, Cr, and Ni each contribute significantly and pose a moderate threat. The Target Hazard Quotient (THQ) values for all pathways of exposure to Pb and Cr in soils were more than 1, which would pose a significant risk to human health in the following order: THQadult female > THQadult male > THQchildren. This study will help to evaluate the human health risk and develop a better understanding of the heavy metal abundance scenario in the agricultural fields adjacent to this highway.
Acute kidney injury in a Malaysian intensive care unit: Assessment of incidence, risk factors, and outcome

Md Ralib A, Mat Nor MB

J Crit Care, 2015 Jun;30(3):636-42.
PMID: 25701354 DOI: 10.1016/j.jcrc.2015.01.018

Acute kidney injury (AKI) is common and carries a high mortality rate. Most epidemiological studies were retrospective and were done in Western populations. We aim to assess its incidence using both urine output and creatinine criteria and its association with risk factors and outcome.
Fulltext Application Of Medicines Scoring System (Medss) : Potential Savings Through Drug Formulary Review Of Sulphonylureas

Ramli A, Aljunid S, Sulong S, Md Yusof FA

Value Health, 2014 Nov;17(7):A749.
PMID: 27202715 DOI: 10.1016/j.jval.2014.08.184
The relationship between the social management of emotional intelligence and academic performance among medical students

Chew BH, Md Zain A, Hassan F

Psychol Health Med, 2015;20(2):198-204.
PMID: 24773524 DOI: 10.1080/13548506.2014.913797

Positive social interaction with peers was said to facilitate cognitive and intellectual development leading to good academic performance. There was paucity of published data on the effect of social management (SM) emotional intelligence (EI) on academic performance. We conducted this study to examine their relationship in the undergraduate medical students in a public medical school in Malaysia. This was a cross-sectional study using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) to measure the SM. The first and final year medical students were invited to participate. Students answered a paper-based demography questionnaire and completed the online MSCEIT in privacy. Independent predictors were identified using multivariate analyses. A total of 163 (84 first year and 79 final year) medical students completed the study (at a response rate of 66.0%). SM score (B = -.10 95% CI -.175 to -.015, p = .021) was significantly related to the continuous assessment (CA) marks (adjusted R(2) = .45, F13,137 = 10.26, p
Fulltext Procalcitonin clearance for early prediction of survival in critically ill patients with severe sepsis

Mat Nor MB, Md Ralib A

Crit Care Res Pract, 2014;2014:819034.
PMID: 24719759 DOI: 10.1155/2014/819034

Introduction. Serum procalcitonin (PCT) diagnosed sepsis in critically ill patients; however, its prediction for survival is not well established. We evaluated the prognostic value of dynamic changes of PCT in sepsis patients. Methods. A prospective observational study was conducted in adult ICU. Patients with systemic inflammatory response syndrome (SIRS) were recruited. Daily PCT were measured for 3 days. 48 h PCT clearance (PCTc-48) was defined as percentage of baseline PCT minus 48 h PCT over baseline PCT. Results. 95 SIRS patients were enrolled (67 sepsis and 28 noninfectious SIRS). 40% patients in the sepsis group died in hospital. Day 1-PCT was associated with diagnosis of sepsis (AUC 0.65 (95% CI, 0.55 to 0.76)) but was not predictive of mortality. In sepsis patients, PCTc-48 was associated with prediction of survival (AUC 0.69 (95% CI, 0.53 to 0.84)). Patients with PCTc-48 > 30% were independently associated with survival (HR 2.90 (95% CI 1.22 to 6.90)). Conclusions. PCTc-48 is associated with prediction of survival in critically ill patients with sepsis. This could assist clinicians in risk stratification; however, the small sample size, and a single-centre study, may limit the generalisability of the finding. This would benefit from replication in future multicentre study.
Fulltext Bilateral retinal vein occlusion and rubeosis irides: lessons to learn

Md Noh UK, Ahem A, Mustapha M

Acta Med Iran, 2013;51(9):657-60.
PMID: 24338200

Uncontrolled hypertension is well- known to give rise to systemic complications involving multiple central organs. Artherosclerosis leads to damage of the retinal vessels wall, contributing to venous stasis, thrombosis and finally, occlusion. Retinal vein occlusions compromise vision through development of ischaemic maculopathy, macular oedema, and rubeotic glaucoma. Laser photocoagulation remains the definitive treatment for ischaemic vein occlusion with secondary neovascularization. Timely treatment with anti- vascular endothelial growth factor prevents development of rubeotic glaucoma. We hereby report an unusual case of bilateral retinal vein occlusion complicated by rubeosis irides, which was successfully managed to improve vision and prevent rubeotic glaucoma.
Neurosyphilis and psychosis

Wahab S, Md Rani SA, Sharis Othman S

Asia Pac Psychiatry, 2013 Apr;5 Suppl 1:90-4.
PMID: 23857843 DOI: 10.1111/appy.12050

Neurosyphilis may presents with a range of psychiatric symptoms. This report illustrates a case of neurosyphilis in a man who presented with psychosis and cognitive dysfunction. Clinical findings and investigations done in the present case showed positive results for syphilis. Reduction of symptoms was noted after treatment with antibiotic. This case further highlights the importance of having high index of suspicion for neurosyphilis in patients presenting with psychiatric symptoms.
Recent trends for practical rehabilitation robotics, current challenges and the future

Yakub F, Md Khudzari AZ, Mori Y

Int J Rehabil Res, 2014 Mar;37(1):9-21.
PMID: 24126254 DOI: 10.1097/MRR.0000000000000035

This paper presents and studies various selected literature primarily from conference proceedings, journals and clinical tests of the robotic, mechatronics, neurology and biomedical engineering of rehabilitation robotic systems. The present paper focuses of three main categories: types of rehabilitation robots, key technologies with current issues and future challenges. Literature on fundamental research with some examples from commercialized robots and new robot development projects related to rehabilitation are introduced. Most of the commercialized robots presented in this paper are well known especially to robotics engineers and scholars in the robotic field, but are less known to humanities scholars. The field of rehabilitation robot research is expanding; in light of this, some of the current issues and future challenges in rehabilitation robot engineering are recalled, examined and clarified with future directions. This paper is concluded with some recommendations with respect to rehabilitation robots.
Phenotypic and genotypic characterization of induced acyclovir-resistant clinical isolates of herpes simplex virus type 1

Hussin A, Md Nor NS, Ibrahim N

Antiviral Res, 2013 Nov;100(2):306-13.
PMID: 24055837 DOI: 10.1016/j.antiviral.2013.09.008

Eleven strains of acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) were generated from HSV-1 clinical isolates by exposure to ACV. Genotype of the thymidine kinase (TK) and DNA polymerase (pol) genes from these mutants were further analyzed. Genotypic analysis revealed four non-synonymous mutations in TK gene associated with gene polymorphism and two to three non-synonymous mutations in DNA pol gene. Seven and six strains contained at least one resistance-associated mutation at TK and DNA pol gene, respectively. Resistance-associated mutations within the TK gene consisted of 64% of non-synonymous frameshift mutations within the homopolymer region of G's and C's, and 36% of non-synonymous nucleotide substitutions of the conserved gene region (C336Y, R51W and R222H), nucleotide that produced stop codon (L288Stop) and two amino acid substitutions outside the conserved region (E39G & L208F). There were 10 non-synonymous amino acid substitutions located outside the conserved region with the unclear significance to confer resistance observed. Resistance-associated mutations in DNA pol gene include insertion of G at the homopolymer region of G's (794-797) and amino acid substitutions inside (V621S) or outside (H1228D) the conserved region. In silico analysis of the mutated TK (C336Y, R51W and L208F), and DNA pol (V621S and H1228D) suggested structural changes that might alter the stability of these proteins. However, there were several mutations with unclear significance to confer ACV-resistance identified, especially mutations outside the conserved region.
Screening heavy metals levels in hair of sanitation workers by X-ray fluorescence analysis

Md Khudzari J, Wagiran H, Hossain I, Ibrahim N

J Environ Radioact, 2013 Jan;115:1-5.
PMID: 22846873 DOI: 10.1016/j.jenvrad.2012.05.013

This work presents a study of human hair as a bio-indicator for detection of heavy metals as part of environmental health surveillance programs project to develop a subject of interest in the biomedical and environmental sciences. A total of 34 hair samples were analyzed that consisting of 29 samples from sanitation workers and five samples from students. The hair samples were prepared and treated in accordance to the International Atomic Energy Agency (IAEA) recommendations. The concentrations of heavy metals were analyzed using the energy dispersive X-ray fluorescence (EDXRF) technique by X-50 Mobile X-ray Fluorescence (XRF) at Oceanography Institute, Universiti Malaysia Terengganu. The performance of EDXRF analyzer was tested by Standard Reference Material (SRM 2711) Montana Soil which was in good agreement with certified value within 14% deviations except for Hg. While seven heavy metals: Mn, Fe, Ni, Cu, Zn, Se, and Sb were detected in both groups, three additional elements, i.e. As, Hg and Pb, were detected only in sanitation workers group. For sanitation workers group, the mean concentration of six elements, Mn, Fe, Cu, Zn, Se, and Sb, shows elevated concentration as compared to the control samples concentration. Results from both groups were compared and discussed in relation to their respective heavy metals concentrations.
Model-aided atpE gene knockout strategy in Escherichia coli for enhanced succinic acid production from glycerol

Mienda BS, Shamsir MS, Md Illias R

J Biomol Struct Dyn, 2016 Aug;34(8):1705-16.
PMID: 26513379 DOI: 10.1080/07391102.2015.1090341

Succinic acid is an important platform chemical with a variety of applications. Model-guided metabolic engineering strategies in Escherichia coli for strain improvement to increase succinic acid production using glucose and glycerol remain largely unexplored. Herein, we report what are, to our knowledge, the first metabolic knockout of the atpE gene to have increased succinic acid production using both glucose and alternative glycerol carbon sources in E. coli. Guided by a genome-scale metabolic model, we engineered the E. coli host to enhance anaerobic production of succinic acid by deleting the atpE gene, thereby generating additional reducing equivalents by blocking H(+) conduction across the mutant cell membrane. This strategy produced 1.58 and .49 g l(-1) of succinic acid from glycerol and glucose substrate, respectively. This work further elucidates a model-guided and/or system-based metabolic engineering, involving only a single-gene deletion strategy for enhanced succinic acid production in E. coli.
Model-assisted formate dehydrogenase-O (fdoH) gene knockout for enhanced succinate production in Escherichia coli from glucose and glycerol carbon sources

Mienda BS, Shamsir MS, Md Illias R

J Biomol Struct Dyn, 2016 Nov;34(11):2305-16.
PMID: 26510527 DOI: 10.1080/07391102.2015.1113387

Succinic acid is an important platform chemical that has broad applications and is been listed as one of the top twelve bio-based chemicals produced from biomass by the US Department of Energy. The metabolic role of Escherichia coli formate dehydrogenase-O (fdoH) under anaerobic conditions in relation to succinic acid production remained largely unspecified. Herein we report, what are to our knowledge, the first metabolic fdoH gene knockout that have enhanced succinate production using glucose and glycerol substrates in E. coli. Using the most recent E. coli reconstruction iJO1366, we engineered its host metabolism to enhance the anaerobic succinate production by deleting the fdoH gene, which blocked H(+) conduction across the mutant cell membrane for the enhanced succinate production. The engineered mutant strain BMS4 showed succinate production of 2.05 g l(-1) (41.2-fold in 7 days) from glycerol and .39 g l(-1) (6.2-fold in 1 day) from glucose. This work revealed that a single deletion of the fdoH gene is sufficient to increase succinate production in E. coli from both glucose and glycerol substrates.

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