Displaying publications 1 - 20 of 35 in total

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  1. Arif MA, Mohamad MS, Abd Latif MS, Deris S, Remli MA, Mohd Daud K, et al.
    Comput Biol Med, 2018 11 01;102:112-119.
    PMID: 30267898 DOI: 10.1016/j.compbiomed.2018.09.015
    Metabolic engineering involves the modification and alteration of metabolic pathways to improve the production of desired substance. The modification can be made using in silico gene knockout simulation that is able to predict and analyse the disrupted genes which may enhance the metabolites production. Global optimization algorithms have been widely used for identifying gene knockout strategies. However, their productions were less than theoretical maximum and the algorithms are easily trapped into local optima. These algorithms also require a very large computation time to obtain acceptable results. This is due to the complexity of the metabolic models which are high dimensional and contain thousands of reactions. In this paper, a hybrid algorithm of Cuckoo Search and Minimization of Metabolic Adjustment is proposed to overcome the aforementioned problems. The hybrid algorithm searches for the near-optimal set of gene knockouts that leads to the overproduction of metabolites. Computational experiments on two sets of genome-scale metabolic models demonstrate that the proposed algorithm is better than the previous works in terms of growth rate, Biomass Product Couple Yield, and computation time.
    Matched MeSH terms: Metabolic Engineering
  2. Azizan KA, Ressom HW, Mendoza ER, Baharum SN
    PeerJ, 2017;5:e3451.
    PMID: 28695065 DOI: 10.7717/peerj.3451
    Lactococcus lactis subsp. cremoris MG1363 is an important starter culture for dairy fermentation. During industrial fermentations, L. lactis is constantly exposed to stresses that affect the growth and performance of the bacterium. Although the response of L. lactis to several stresses has been described, the adaptation mechanisms at the level of in vivo fluxes have seldom been described. To gain insights into cellular metabolism, 13C metabolic flux analysis and gas chromatography mass spectrometry (GC-MS) were used to measure the flux ratios of active pathways in the central metabolism of L. lactis when subjected to three conditions varying in temperature (30°C, 37°C) and agitation (with and without agitation at 150 rpm). Collectively, the concentrations of proteinogenic amino acids (PAAs) and free fatty acids (FAAs) were compared, and Pearson correlation analysis (r) was calculated to measure the pairwise relationship between PAAs. Branched chain and aromatic amino acids, threonine, serine, lysine and histidine were correlated strongly, suggesting changes in flux regulation in glycolysis, the pentose phosphate (PP) pathway, malic enzyme and anaplerotic reaction catalysed by pyruvate carboxylase (pycA). Flux ratio analysis revealed that glucose was mainly converted by glycolysis, highlighting the stability of L. lactis' central carbon metabolism despite different conditions. Higher flux ratios through oxaloacetate (OAA) from pyruvate (PYR) reaction in all conditions suggested the activation of pyruvate carboxylate (pycA) in L. lactis, in response to acid stress during exponential phase. Subsequently, more significant flux ratio differences were seen through the oxidative and non-oxidative pentose phosphate (PP) pathways, malic enzyme, and serine and C1 metabolism, suggesting NADPH requirements in response to environmental stimuli. These reactions could play an important role in optimization strategies for metabolic engineering in L. lactis. Overall, the integration of systematic analysis of amino acids and flux ratio analysis provides a systems-level understanding of how L. lactis regulates central metabolism under various conditions.
    Matched MeSH terms: Metabolic Engineering
  3. Baharum SN, Azizan KA
    Adv Exp Med Biol, 2018 11 2;1102:51-68.
    PMID: 30382568 DOI: 10.1007/978-3-319-98758-3_4
    Over the last decade, metabolomics has continued to grow rapidly and is considered a dynamic technology in envisaging and elucidating complex phenotypes in systems biology area. The advantage of metabolomics compared to other omics technologies such as transcriptomics and proteomics is that these later omics only consider the intermediate steps in the central dogma pathway (mRNA and protein expression). Meanwhile, metabolomics reveals the downstream products of gene and expression of proteins. The most frequently used tools are nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Some of the common MS-based analyses are gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). These high-throughput instruments play an extremely crucial role in discovery metabolomics to generate data needed for further analysis. In this chapter, the concept of metabolomics in the context of systems biology is discussed and provides examples of its application in human disease studies, plant responses towards stress and abiotic resistance and also microbial metabolomics for biotechnology applications. Lastly, a few case studies of metabolomics analysis are also presented, for example, investigation of an aromatic herbal plant, Persicaria minor metabolome and microbial metabolomics for metabolic engineering applications.
    Matched MeSH terms: Metabolic Engineering
  4. Baradaran A, Sieo CC, Foo HL, Illias RM, Yusoff K, Rahim RA
    Biotechnol Lett, 2013 Feb;35(2):233-8.
    PMID: 23076361 DOI: 10.1007/s10529-012-1059-4
    Fifty signal peptides of Pediococcus pentosaceus were characterized by in silico analysis and, based on the physicochemical analysis, (two potential signal peptides Spk1 and Spk3 were identified). The coding sequences of SP were amplified and fused to the gene coding for green fluorescent protein (GFP) and cloned into Lactococcus lactis pNZ8048 and pMG36e vectors, respectively. Western blot analysis indicated that the GFP proteins were secreted using both heterologous SPs. ELISA showed that the secretion efficiency of GFP using Spk1 (0.64 μg/ml) was similar to using Usp45 (0.62 μg/ml) and Spk3 (0.58 μg/ml).
    Matched MeSH terms: Metabolic Engineering*
  5. Daud KM, Mohamad MS, Zakaria Z, Hassan R, Shah ZA, Deris S, et al.
    Comput Biol Med, 2019 10;113:103390.
    PMID: 31450056 DOI: 10.1016/j.compbiomed.2019.103390
    Metabolic engineering is defined as improving the cellular activities of an organism by manipulating the metabolic, signal or regulatory network. In silico reaction knockout simulation is one of the techniques applied to analyse the effects of genetic perturbations on metabolite production. Many methods consider growth coupling as the objective function, whereby it searches for mutants that maximise the growth and production rate. However, the final goal is to increase the production rate. Furthermore, they produce one single solution, though in reality, cells do not focus on one objective and they need to consider various different competing objectives. In this work, a method, termed ndsDSAFBA (non-dominated sorting Differential Search Algorithm and Flux Balance Analysis), has been developed to find the reaction knockouts involved in maximising the production rate and growth rate of the mutant, by incorporating Pareto dominance concepts. The proposed ndsDSAFBA method was validated using three genome-scale metabolic models. We obtained a set of non-dominated solutions, with each solution representing a different mutant strain. The results obtained were compared with the single objective optimisation (SOO) and multi-objective optimisation (MOO) methods. The results demonstrate that ndsDSAFBA is better than the other methods in terms of production rate and growth rate.
    Matched MeSH terms: Metabolic Engineering*
  6. Gan HM, Thomas BN, Cavanaugh NT, Morales GH, Mayers AN, Savka MA, et al.
    PeerJ, 2017;5:e4030.
    PMID: 29158974 DOI: 10.7717/peerj.4030
    In industry, the yeast Rhodotorula mucilaginosa is commonly used for the production of carotenoids. The production of carotenoids is important because they are used as natural colorants in food and some carotenoids are precursors of retinol (vitamin A). However, the identification and molecular characterization of the carotenoid pathway/s in species belonging to the genus Rhodotorula is scarce due to the lack of genomic information thus potentially impeding effective metabolic engineering of these yeast strains for improved carotenoid production. In this study, we report the isolation, identification, characterization and the whole nuclear genome and mitogenome sequence of the endophyte R. mucilaginosa RIT389 isolated from Distemonanthus benthamianus, a plant known for its anti-fungal and antibacterial properties and commonly used as chewing sticks. The assembled genome of R. mucilaginosa RIT389 is 19 Mbp in length with an estimated genomic heterozygosity of 9.29%. Whole genome phylogeny supports the species designation of strain RIT389 within the genus in addition to supporting the monophyly of the currently sequenced Rhodotorula species. Further, we report for the first time, the recovery of the complete mitochondrial genome of R. mucilaginosa using the genome skimming approach. The assembled mitogenome is at least 7,000 bases larger than that of Rhodotorula taiwanensis which is largely attributed to the presence of large intronic regions containing open reading frames coding for homing endonuclease from the LAGLIDADG and GIY-YIG families. Furthermore, genomic regions containing the key genes for carotenoid production were identified in R. mucilaginosa RIT389, revealing differences in gene synteny that may play a role in the regulation of the biotechnologically important carotenoid synthesis pathways in yeasts.
    Matched MeSH terms: Metabolic Engineering
  7. Goh HH
    Adv Exp Med Biol, 2018 11 2;1102:69-80.
    PMID: 30382569 DOI: 10.1007/978-3-319-98758-3_5
    This chapter introduces different aspects of bioinformatics with a brief discussion in the systems biology context. Example applications in network pharmacology of traditional Chinese medicine, systems metabolic engineering, and plant genome-scale modelling are described. Lastly, this chapter concludes on how bioinformatics helps to integrate omics data derived from various studies described in previous chapters for a holistic understanding of secondary metabolite production in P. minus.
    Matched MeSH terms: Metabolic Engineering*
  8. Hatti-Kaul R, Chen L, Dishisha T, Enshasy HE
    FEMS Microbiol Lett, 2018 10 01;365(20).
    PMID: 30169778 DOI: 10.1093/femsle/fny213
    Lactic acid bacteria constitute a diverse group of industrially significant, safe microorganisms that are primarily used as starter cultures and probiotics, and are also being developed as production systems in industrial biotechnology for biocatalysis and transformation of renewable feedstocks to commodity- and high-value chemicals, and health products. Development of strains, which was initially based mainly on natural approaches, is also achieved by metabolic engineering that has been facilitated by the availability of genome sequences and genetic tools for transformation of some of the bacterial strains. The aim of this paper is to provide a brief overview of the potential of lactic acid bacteria as biological catalysts for production of different organic compounds for food and non-food sectors based on their diversity, metabolic- and stress tolerance features, as well as the use of genetic/metabolic engineering tools for enhancing their capabilities.
    Matched MeSH terms: Metabolic Engineering/methods
  9. Ho CL
    Front Plant Sci, 2015;6:1057.
    PMID: 26635861 DOI: 10.3389/fpls.2015.01057
    Many algae are rich sources of sulfated polysaccharides with biological activities. The physicochemical/rheological properties and biological activities of sulfated polysaccharides are affected by the pattern and number of sulfate moieties. Sulfation of carbohydrates is catalyzed by carbohydrate sulfotransferases (CHSTs) while modification of sulfate moieties on sulfated polysaccharides was presumably catalyzed by sulfatases including formylglycine-dependent sulfatases (FGly-SULFs). Post-translationally modification of Cys to FGly in FGly-SULFs by sulfatase modifiying factors (SUMFs) is necessary for the activity of this enzyme. The aims of this study are to mine for sequences encoding algal CHSTs, FGly-SULFs and putative SUMFs from the fully sequenced algal genomes and to infer their phylogenetic relationships to their well characterized counterparts from other organisms. Algal sequences encoding CHSTs, FGly-SULFs, SUMFs, and SUMF-like proteins were successfully identified from green and brown algae. However, red algal FGly-SULFs and SUMFs were not identified. In addition, a group of SUMF-like sequences with different gene structure and possibly different functions were identified for green, brown and red algae. The phylogeny of these putative genes contributes to the corpus of knowledge of an unexplored area. The analyses of these putative genes contribute toward future production of existing and new sulfated carbohydrate polymers through enzymatic synthesis and metabolic engineering.
    Matched MeSH terms: Metabolic Engineering
  10. Huong KH, Sevakumaran V, Amirul AA
    Crit Rev Biotechnol, 2021 Jun;41(4):474-490.
    PMID: 33726581 DOI: 10.1080/07388551.2020.1869685
    Polyhydroxyalkanoate (PHA) is a biogenic polymer that has the potential to substitute synthetic plastic in numerous applications. This is due to its unique attribute of being a biodegradable and biocompatible thermoplastic, achievable through microbial fermentation from a broad utilizable range of renewable resources. Among all the PHAs discovered, poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] stands out as a next generation healthcare biomaterial for having high biopharmaceutical and medical value since it is highly compatible to mammalian tissue. This review provides a critical assessment and complete overview of the development and trend of P(3HB-co-4HB) research over the last few decades, highlighting aspects from the microbial strain discovery to metabolic engineering and bioprocess cultivation strategies. The article also outlines the relevance of P(3HB-co-4HB) as a material for high value-added products in numerous healthcare-related applications.
    Matched MeSH terms: Metabolic Engineering
  11. Ikram NK, Zhan X, Pan XW, King BC, Simonsen HT
    Front Plant Sci, 2015;6:129.
    PMID: 25852702 DOI: 10.3389/fpls.2015.00129
    Plants biosynthesize a great diversity of biologically active small molecules of interest for fragrances, flavors, and pharmaceuticals. Among specialized metabolites, terpenoids represent the greatest molecular diversity. Many terpenoids are very complex, and total chemical synthesis often requires many steps and difficult chemical reactions, resulting in a low final yield or incorrect stereochemistry. Several drug candidates with terpene skeletons are difficult to obtain by chemical synthesis due to their large number of chiral centers. Thus, biological production remains the preferred method for industrial production for many of these compounds. However, because these chemicals are often found in low abundance in the native plant, or are produced in plants which are difficult to cultivate, there is great interest in engineering increased production or expression of the biosynthetic pathways in heterologous hosts. Although there are many examples of successful engineering of microbes such as yeast or bacteria to produce these compounds, this often requires extensive changes to the host organism's metabolism. Optimization of plant gene expression, post-translational protein modifications, subcellular localization, and other factors often present challenges. To address the future demand for natural products used as drugs, new platforms are being established that are better suited for heterologous production of plant metabolites. Specifically, direct metabolic engineering of plants can provide effective heterologous expression for production of valuable plant-derived natural products. In this review, our primary focus is on small terpenoids and we discuss the benefits of plant expression platforms and provide several successful examples of stable production of small terpenoids in plants.
    Matched MeSH terms: Metabolic Engineering
  12. Jin H, Wang Y, Zhao P, Wang L, Zhang S, Meng D, et al.
    J Agric Food Chem, 2021 Oct 27;69(42):12385-12401.
    PMID: 34649432 DOI: 10.1021/acs.jafc.1c04632
    Numerous plant secondary metabolites have remarkable impacts on both food supplements and pharmaceuticals for human health improvement. However, higher plants can only generate small amounts of these chemicals with specific temporal and spatial arrangements, which are unable to satisfy the expanding market demands. Cyanobacteria can directly utilize CO2, light energy, and inorganic nutrients to synthesize versatile plant-specific photosynthetic intermediates and organic compounds in large-scale photobioreactors with outstanding economic merit. Thus, they have been rapidly developed as a "green" chassis for the synthesis of bioproducts. Flavonoids, chemical compounds based on aromatic amino acids, are considered to be indispensable components in a variety of nutraceutical, pharmaceutical, and cosmetic applications. In contrast to heterotrophic metabolic engineering pioneers, such as yeast and Escherichia coli, information about the biosynthesis flavonoids and their derivatives is less comprehensive than that of their photosynthetic counterparts. Here, we review both benefits and challenges to promote cyanobacterial cell factories for flavonoid biosynthesis. With increasing concerns about global environmental issues and food security, we are confident that energy self-supporting cyanobacteria will attract increasing attention for the generation of different kinds of bioproducts. We hope that the work presented here will serve as an index and encourage more scientists to join in the relevant research area.
    Matched MeSH terms: Metabolic Engineering
  13. Kabir, M.U., Abdulkarim, S.M., Son, R., Azizah, A.H., Saari, N.B.
    MyJurnal
    Phytochemicals belonging to the group’s phenols, terpenes, betalains, organosulfides, indoles and protein inhibitors are important components in fruits, vegetables, legumes, whole grains and nuts that have health promoting benefits and a variety of applications in food and pharmaceutical industries. Initially only a few of these important phytochemicals are produced commercially by chemical synthesis. However, recent developments in the field of biotechnology have provided metabolic engineering strategies that use microorganisms as cell factories for high production of these products. This review will discuss the general biosynthetic pathways, metabolic engineering and optimization strategies of functional phytochemicals that have received a lot of attention from investigators.
    Matched MeSH terms: Metabolic Engineering
  14. Kato T, Azegami J, Yokomori A, Dohra H, El Enshasy HA, Park EY
    BMC Genomics, 2020 Apr 23;21(1):319.
    PMID: 32326906 DOI: 10.1186/s12864-020-6709-7
    BACKGROUND: Ashbya gossypii naturally overproduces riboflavin and has been utilized for industrial riboflavin production. To improve riboflavin production, various approaches have been developed. In this study, to investigate the change in metabolism of a riboflavin-overproducing mutant, namely, the W122032 strain (MT strain) that was isolated by disparity mutagenesis, genomic analysis was carried out.

    RESULTS: In the genomic analysis, 33 homozygous and 1377 heterozygous mutations in the coding sequences of the genome of MT strain were detected. Among these heterozygous mutations, the proportion of mutated reads in each gene was different, ranging from 21 to 75%. These results suggest that the MT strain may contain multiple nuclei containing different mutations. We tried to isolate haploid spores from the MT strain to prove its ploidy, but this strain did not sporulate under the conditions tested. Heterozygous mutations detected in genes which are important for sporulation likely contribute to the sporulation deficiency of the MT strain. Homozygous and heterozygous mutations were found in genes encoding enzymes involved in amino acid metabolism, the TCA cycle, purine and pyrimidine nucleotide metabolism and the DNA mismatch repair system. One homozygous mutation in AgILV2 gene encoding acetohydroxyacid synthase, which is also a flavoprotein in mitochondria, was found. Gene ontology (GO) enrichment analysis showed heterozygous mutations in all 22 DNA helicase genes and genes involved in oxidation-reduction process.

    CONCLUSION: This study suggests that oxidative stress and the aging of cells were involved in the riboflavin over-production in A. gossypii riboflavin over-producing mutant and provides new insights into riboflavin production in A. gossypii and the usefulness of disparity mutagenesis for the creation of new types of mutants for metabolic engineering.

    Matched MeSH terms: Metabolic Engineering/methods
  15. Ku Nurul Aqmar Ku Bahaudin, Ahmad Bazli Ramzi, Syarul Nataqain Baharum, Suriana Sabri, Adam Leow Thean Chor, Tewin Tencomnao
    Sains Malaysiana, 2018;47:3077-3084.
    Flavonoid is an industrially-important compound due to its high pharmaceutical and cosmeceutical values. However,
    conventional methods in extracting and synthesizing flavonoids are costly, laborious and not sustainable due to small
    amount of natural flavonoids, large amounts of chemicals and space used. Biotechnological production of flavonoids
    represents a viable and sustainable route especially through the use of metabolic engineering strategies in microbial
    production hosts. In this review, we will highlight recent strategies for the improving the production of flavonoids
    using synthetic biology approaches in particular the innovative strategies of genetically-encoded biosensors for in
    vivo metabolite analysis and high-throughput screening methods using fluorescence-activated cell sorting (FACS).
    Implementation of transcription factor based-biosensor for microbial flavonoid production and integration of systems
    and synthetic biology approaches for natural product development will also be discussed.
    Matched MeSH terms: Metabolic Engineering
  16. Lee MK, Mohamad MS, Choon YW, Mohd Daud K, Nasarudin NA, Ismail MA, et al.
    J Integr Bioinform, 2020 May 06;17(1).
    PMID: 32374287 DOI: 10.1515/jib-2019-0073
    The metabolic network is the reconstruction of the metabolic pathway of an organism that is used to represent the interaction between enzymes and metabolites in genome level. Meanwhile, metabolic engineering is a process that modifies the metabolic network of a cell to increase the production of metabolites. However, the metabolic networks are too complex that cause problem in identifying near-optimal knockout genes/reactions for maximizing the metabolite's production. Therefore, through constraint-based modelling, various metaheuristic algorithms have been improvised to optimize the desired phenotypes. In this paper, PSOMOMA was compared with CSMOMA and ABCMOMA for maximizing the production of succinic acid in E. coli. Furthermore, the results obtained from PSOMOMA were validated with results from the wet lab experiment.
    Matched MeSH terms: Metabolic Engineering
  17. Leong YK, Show PL, Ooi CW, Ling TC, Lan JC
    J Biotechnol, 2014 Jun 20;180:52-65.
    PMID: 24698847 DOI: 10.1016/j.jbiotec.2014.03.020
    Pursuing the current trend, the "green-polymers", polyhydroxyalkanoates (PHAs) which are degradable and made from renewable sources have been a potential substitute for synthetic plastics. Due to the increasing concern towards escalating crude oil price, depleting petroleum resource and environmental damages done by plastics, PHAs have gained more and more attractions, both from industry and research. From the view point of Escherichia coli, a microorganism that used in the biopolymer large scale production, this paper describes the backgrounds of PHA and summarizes the current advances in PHA developments. In the short-chain-length (scl) PHAs section, the study of poly[(R)-3-hydroxybutyrate] [P(3HB)] as model polymer, ultra-high-molecular-weight P(3HB) which rarely discussed, and P(3HB-co-3HV), another commercialized PHA polymer are included. Other than that, this review also shed some light on the new members of PHA family, lactate-based PHAs and P(3HP) with topics such as block copolymers and invention of novel biopolymers. Flexibility of microorganisms in utilizing different carbon sources to accumulate medium-chain-length (mcl) PHAs and lastly, the promising scl-mcl-PHAs with interesting properties are also discussed.
    Matched MeSH terms: Metabolic Engineering/trends*
  18. Lu SJ, Salleh AH, Mohamad MS, Deris S, Omatu S, Yoshioka M
    Comput Biol Chem, 2014 12;53PB:175-183.
    PMID: 25462325 DOI: 10.1016/j.compbiolchem.2014.09.008
    Reconstructions of genome-scale metabolic networks from different organisms have become popular in recent years. Metabolic engineering can simulate the reconstruction process to obtain desirable phenotypes. In previous studies, optimization algorithms have been implemented to identify the near-optimal sets of knockout genes for improving metabolite production. However, previous works contained premature convergence and the stop criteria were not clear for each case. Therefore, this study proposes an algorithm that is a hybrid of the ant colony optimization algorithm and flux balance analysis (ACOFBA) to predict near optimal sets of gene knockouts in an effort to maximize growth rates and the production of certain metabolites. Here, we present a case study that uses Baker's yeast, also known as Saccharomyces cerevisiae, as the model organism and target the rate of vanillin production for optimization. The results of this study are the growth rate of the model organism after gene deletion and a list of knockout genes. The ACOFBA algorithm was found to improve the yield of vanillin in terms of growth rate and production compared with the previous algorithms.
    Matched MeSH terms: Metabolic Engineering
  19. Man MY, Mohamad MS, Choon YW, Ismail MA
    J Integr Bioinform, 2021 Aug 04;18(3).
    PMID: 34348418 DOI: 10.1515/jib-2020-0037
    Microorganisms commonly produce many high-demand industrial products like fuels, food, vitamins, and other chemicals. Microbial strains are the strains of microorganisms, which can be optimized to improve their technological properties through metabolic engineering. Metabolic engineering is the process of overcoming cellular regulation in order to achieve a desired product or to generate a new product that the host cells do not usually need to produce. The prediction of genetic manipulations such as gene knockout is part of metabolic engineering. Gene knockout can be used to optimize the microbial strains, such as to maximize the production rate of chemicals of interest. Metabolic and genetic engineering is important in producing the chemicals of interest as, without them, the product yields of many microorganisms are normally low. As a result, the aim of this paper is to propose a combination of the Bat algorithm and the minimization of metabolic adjustment (BATMOMA) to predict which genes to knock out in order to increase the succinate and lactate production rates in Escherichia coli (E. coli).
    Matched MeSH terms: Metabolic Engineering
  20. Mienda BS
    J Biomol Struct Dyn, 2017 Jul;35(9):1863-1873.
    PMID: 27251747 DOI: 10.1080/07391102.2016.1197153
    Genome-scale metabolic models (GEMs) have been developed and used in guiding systems' metabolic engineering strategies for strain design and development. This strategy has been used in fermentative production of bio-based industrial chemicals and fuels from alternative carbon sources. However, computer-aided hypotheses building using established algorithms and software platforms for biological discovery can be integrated into the pipeline for strain design strategy to create superior strains of microorganisms for targeted biosynthetic goals. Here, I described an integrated workflow strategy using GEMs for strain design and biological discovery. Specific case studies of strain design and biological discovery using Escherichia coli genome-scale model are presented and discussed. The integrated workflow presented herein, when applied carefully would help guide future design strategies for high-performance microbial strains that have existing and forthcoming genome-scale metabolic models.
    Matched MeSH terms: Metabolic Engineering
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