Analyses of extracellular protein production in Bacillus subtilis – I: Genome-scale metabolic model reconstruction based on updated gene-enzyme-reaction data

Kocabaş, Pınar; Çalı́k, Pınar; Çalık, Güzide; Özdamar, Tunçer H.

doi:10.1016/j.bej.2017.07.005

Cited by 24 publications

(19 citation statements)

References 37 publications

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“…When fed‐batch operation is shifted to batch operation, as C G → 0 there is no uptake of glucose during the Δ t B periods (Figure S1). To determine its influences on the flow of C molecules through the intracellular reaction network quantitatively, metabolic flux analysis (MFA) needs to be carried out at mathematically well‐defined states in each period . Qualitatively, one can predict that with the start of the fed‐batch period Δ t FB , the continuously fed glucose is transported into the cytoplasm with a high uptake rate where it is converted to precursor metabolites and Gibbs free energy is captured in the form of high energy phosphate bonds in ATP or as reduction equivalents of two related but distinct compounds NADPH/NADP + and NADH/NAD + .…”

Section: Resultsmentioning

confidence: 99%

“…To determine its influences on the flow of C molecules through the intracellular reaction network quantitatively, metabolic flux analysis (MFA) needs to be carried out at mathematically well-defined states in each period. 29 Qualitatively, one can predict that with the start of the fed-batch period Δt FB , the continuously fed glucose is transported into the cytoplasm with a high uptake rate where it is converted to precursor metabolites and Gibbs free energy is captured in the form of high energy phosphate bonds in ATP or as reduction equivalents of two related but distinct compounds NADPH/NADP + and NADH/NAD + . Consecutively, formation of macromolecules which constitute the major part of the cell requires synthesis of the building blocks followed by their polymerization; in this, the cell controls protein synthesis in ribosomes and thus the energy expenditure.…”

Section: Comparison Of Fed-batch Operations and Hfbbs With Glucosementioning

confidence: 99%

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Hybrid fed‐batch bioreactor operation design: control of substrate uptake enhances recombinant protein production in high‐cell‐density fermentations

Çalı́k

Hoxha

Çalık

et al. 2018

J of Chemical Tech & Biotech

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BACKGROUND The hybrid fed‐batch bioreactor (HFBB) operation is a novel design method for high‐cell‐density fermentations. It employs fed‐batch and batch operations, starting with fed‐batch that in turn shifts to the next, and proceeds in successive cycles to enhance production and productivity by controlling the substrate uptake rate. RESULTS The method was tested for the production of recombinant human growth hormone (rhGH) in Pichia pastoris under GAP promoter with carbon sources of (i) glucose and (ii) pre‐treated hydrolyzed sugar‐beet molasses containing equimolar glucose and fructose. The superior strategies were: (i) GH2, a HFBB with glucose feeding composed of ΔtFB = 1.5 h fed‐batch periods with continuous‐feed stream designed with the pre‐determined growth rate µ = 0.10 h−1, which shift in turn to ΔtB = 0.5 h batch periods; and (ii) MH2, a HFBB with molasses feeding designed in a similar way to GH2. The highest rhGH production attained in GH2 was 611 mg dm−3 at 8 h, whereas it was 625 mg dm−3 at 13.5 h in MH2. In GH2, rhGH production increased 1.37‐fold in half the cultivation time of GH2. However, in MH2 with dual carbon sources enriched with other substrates, higher rhGH production was obtained at the cost of lower productivity. CONCLUSION The HFBB is a powerful design method with a single carbon source which improves the productivity of high‐cell‐density fermentations. However, with molasses upon shifting to batch operations, the uptake of accumulated fructose is continued. Thus, the glamour of the HFBB is hindered for complex media fermentations to an extent, because multi‐carbon sources contribute to the growth during the batch periods by lengthening the cultivation time. © 2018 Society of Chemical Industry

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Section: Resultsmentioning

confidence: 99%

Section: Comparison Of Fed-batch Operations and Hfbbs With Glucosementioning

confidence: 99%

Hybrid fed‐batch bioreactor operation design: control of substrate uptake enhances recombinant protein production in high‐cell‐density fermentations

Çalı́k

Hoxha

Çalık

et al. 2018

J of Chemical Tech & Biotech

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“…; Calik and Ileri ; Kocabas et al . ). The network contained the central carbon metabolism including the glycolysis, the pentose phosphate pathway (PPP), the gluconeogenic, the anaplerotic pathways and the tricarboxylic acid (TCA) cycle.…”

Section: Methodsmentioning

confidence: 97%

Central carbon metabolism influences cellulase production in Bacillus licheniformis

Wang

Liu

et al. 2017

Lett Appl Microbiol

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Cellulase is very important in the field of agriculture and bioenergy because of its degrading effect on cellulosic biomass. This study presented the effect of central carbon metabolism on cellulase production in Bacillus licheniformis. The study also provided a holistic view of the physiological status in B. licheniformis. The shifted metabolism provided a quantitative evaluation of the biosynthesis of cellulase and a priority ranked target list for further strain engineering.

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“…Bacillus subtilis is a representative Gram-positive bacterium that has value to industrial biotechnology in the production of various enzymes and proteins [22, 23]. GEMs reconstructed for B. subtilis include iYO844 [24], a GEM by Goelzer et al [25], iBsu1103 [26], iBsu1103V2 [27], iBsu1147 [28], and iBsu1144 [29]. The latest version, iBsu1144, built on the basis of the re-annotated genome information [30], was developed by incorporating thermodynamic information on the standard molar Gibbs free energy change for each reaction, in order to improve the accuracy and consistency of the reversibility of intracellular reactions.…”

Section: Current Status Of Reconstructed Genome-scale Metabolic Modelsmentioning

confidence: 99%

Current status and applications of genome-scale metabolic models

Gu¹,

Kim²,

Kim³

et al. 2019

Genome Biol

520

472

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Genome-scale metabolic models (GEMs) computationally describe gene-protein-reaction associations for entire metabolic genes in an organism, and can be simulated to predict metabolic fluxes for various systems-level metabolic studies. Since the first GEM for Haemophilus influenzae was reported in 1999, advances have been made to develop and simulate GEMs for an increasing number of organisms across bacteria, archaea, and eukarya. Here, we review current reconstructed GEMs and discuss their applications, including strain development for chemicals and materials production, drug targeting in pathogens, prediction of enzyme functions, pan-reactome analysis, modeling interactions among multiple cells or organisms, and understanding human diseases.

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Analyses of extracellular protein production in Bacillus subtilis – I: Genome-scale metabolic model reconstruction based on updated gene-enzyme-reaction data

Cited by 24 publications

References 37 publications

Hybrid fed‐batch bioreactor operation design: control of substrate uptake enhances recombinant protein production in high‐cell‐density fermentations

Hybrid fed‐batch bioreactor operation design: control of substrate uptake enhances recombinant protein production in high‐cell‐density fermentations

Central carbon metabolism influences cellulase production in Bacillus licheniformis

Current status and applications of genome-scale metabolic models

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