Artificial neural network‐genetic algorithm (ANN‐GA) based medium optimization for the production of human interferon gamma (hIFN‐γ) in <i>Kluyveromyces lactis</i> cell factory

Unni, Silpa; Prabhu, Ashish A.; Pandey, Rajat; Hande, Rohit; Veeranki, Venkata Dasu

doi:10.1002/cjce.23350

Cited by 26 publications

(12 citation statements)

References 60 publications

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“…In order to predict the performance of the fermentation processes, it is of key importance to gain knowledge on operations involving change with respect to time and behavior of microorganism in presence of different substrate concentration. Substrate inhibition often occurs at elevated carbon source/substrate concentrations which may be due to multiple substrate molecules binding to the same site [48]. Among the various unstructured model used, three parameter Aiba model showed relatively high R 2 value of 0.82 and inhibition concentration (88.87 g/L), which was closer to the experimental data.…”

Section: Discussionsupporting

confidence: 58%

Bioproduction of succinic acid from xylose by engineered Yarrowia lipolytica without pH control

Prabhu

Amaro

Lin

et al. 2020

Preprint

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Background Xylose is a most prevalent sugar available in hemicellulose fraction of lignocellulosic biomass (LCB) and of great interest for the green economy. Unfortunately, most of the cell factories cannot inherently metabolize xylose as sole carbon source. Yarrowia lipolytica is a non-conventional yeast to produce industrially important metabolites, and it is able to metabolize a large variety of substrates including both hydrophilic and hydrophobic carbon sources. However, Y. lipolytica lacks effective metabolic pathway for xylose uptake and only scarce information is available on utilization of xylose. For the economically feasible of LCB-based biorefineries, effective utilization of both pentose and hexose sugars is obligatory. Results In the present study, succinic acid (SA) production from xylose by Y. lipolytica was examined. To this end, Y. lipolytica PSA02004 strain was engineered by overexpressing pentose pathway cassette comprising of xylose reductase ( XR ), xylitol dehydrogenase ( XDH ) and xylulose kinase ( XK ) gene. The recombinant strain exhibited a robust growth on xylose as sole carbon source and accumulated SA (3.8 g/L) with a yield of 0.19 g/g in shake flask studies. Substrate inhibition studies revealed a marked negative impact on cell growth and product formation above 60 g/L xylose concentration. The modelling based on inhibition kinetics revealed that Aiba model showed better fit with experimental data, which resulted the correlation coefficient (R 2 ) of 0.82 and inhibition constant (K I ) 88.9 g/L. The batch cultivation of recombinant strain in bioreactor resulted in a maximum biomass concentration of 7.3 g/L and SA titer of 11.2 g/L with the yield of 0.18 g/g. Similar results in term of cell growth and SA production were obtained with xylose-rich hydrolysate derived from sugarcane bagasse. The fed-batch fermentation yielded biomass concentration of 11.8 g/L (OD 600 : 56.1) and SA titer of 22.3 g/L with a gradual decrease in pH below 4.0. Acetic acid was obtained as a main byproduct in all the fermentations. Conclusion The recombinant strain displayed potential bioconversion of xylose to succinic acid. Further this study provided a new insight on conversion of LCB into value-added products. To the best of our knowledge, this is the first study on SA production by Y. lipolytica using xylose as a sole carbon source.

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Section: Discussionsupporting

confidence: 58%

Bioproduction of succinic acid from xylose by engineered Yarrowia lipolytica without pH control

Prabhu

Amaro

Lin

et al. 2020

Preprint

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“…In DOE, various process parameters can be changed in a set of experimental trials, and a small number of experiments are enough to decide the effect of the various parameters and to select the most important ones (Papaneophytou and Kontopidis, 2014;Kumar et al, 2019;Shekhawat et al, 2019). In one study, RSM was applied to develop a defined medium to enhance human interferon gamma production (Unni et al, 2019). Using DoE, the signal peptide was selected and optimal growth conditions were established for recombinant antibody fragment production in the periplasm of E. coli (Kasli et al, 2019).…”

Section: Design Of Experiments Approachmentioning

confidence: 99%

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Tripathi

Shrivastava

2019

Front. Bioeng. Biotechnol.

369

243

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Infectious diseases, along with cancers, are among the main causes of death among humans worldwide. The production of therapeutic proteins for treating diseases at large scale for millions of individuals is one of the essential needs of mankind. Recent progress in the area of recombinant DNA technologies has paved the way to producing recombinant proteins that can be used as therapeutics, vaccines, and diagnostic reagents. Recombinant proteins for these applications are mainly produced using prokaryotic and eukaryotic expression host systems such as mammalian cells, bacteria, yeast, insect cells, and transgenic plants at laboratory scale as well as in large-scale settings. The development of efficient bioprocessing strategies is crucial for industrial production of recombinant proteins of therapeutic and prophylactic importance. Recently, advances have been made in the various areas of bioprocessing and are being utilized to develop effective processes for producing recombinant proteins. These include the use of high-throughput devices for effective bioprocess optimization and of disposable systems, continuous upstream processing, continuous chromatography, integrated continuous bioprocessing, Quality by Design, and process analytical technologies to achieve quality product with higher yield. This review summarizes recent developments in the bioprocessing of recombinant proteins, including in various expression systems, bioprocess development, and the upstream and downstream processing of recombinant proteins.

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“…During training the data over fits and substantial error will be accumulated on the validation. When the error on the validation reaches the threshold point the weights and biases are adjusted to minimize the error [17,18]. Network topology have a crucial role in predicting results, the input-output neuron of ANN is the resemblance of input and output data used in this study.…”

Section: Optimization Of Process Parameters Using Artificial Neural Nmentioning

confidence: 99%

Biovalorisation of crude glycerol and xylose into xylitol by oleaginous yeast Yarrowia lipolytica

Prabhu

Thomas

Amaro

et al. 2020

Preprint

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Background: Xylitol is a commercially important chemical with multiple applications in food and pharmaceutical industries. According to the US Department of Energy, xylitol is among the twelve platform chemicals that can be produced from biomass. The chemical method for xylitol synthesis is however expensive and energy intensive. In contrast, the biological route involving microbial cell factories offers a potential cost-effective alternative process. The bioprocess occurs under ambient conditions and makes use of biocatalysts which can be sourced from renewable carbon coming from a variety of cheap feedstocks classified as wastes. Result: In this study, biotransformation of xylose to xylitol was investigated using Yarrowia lipolytica an oleaginous yeast grown on glycerol/glucose screening of primary carbon source, media optimisation in shake flask, scale up in bioreactor and downstream processing of xylitol were carried out. With the two step medium optimization involving central composite design and artificial neural network coupled with genetic algorithm, the yeast amassed 53.2 g/L of xylitol using glycerol and xylose with a bioconversion yield of 0.97 g/g. Similar results were obtained when pure glycerol was substituted with crude glycerol from biodiesel industry (titer: 50.5 g/L; yield: 0.92 g/g). Even when xylose from lignocellulosic hydrolysate was used as opposed to pure xylose, a xylitol yield of 0.54 g/g was achieved. Xylitol was successfully crystallized from fermented broth using pure glycerol/xylose and crude glycerol /xylose with a recovery of 35 and 39.45%, respectively. Conclusion: To the best of the author’s knowledge, this is the first study demonstrating the potential of Y. lipolytica as microbial cell factory for xylitol synthesis from inexpensive feedstocks. The results obtained are competitive with other xylitol producing organisms.

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Artificial neural network‐genetic algorithm (ANN‐GA) based medium optimization for the production of human interferon gamma (hIFN‐γ) in Kluyveromyces lactis cell factory

Cited by 26 publications

References 60 publications

Bioproduction of succinic acid from xylose by engineered Yarrowia lipolytica without pH control

Bioproduction of succinic acid from xylose by engineered Yarrowia lipolytica without pH control

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Biovalorisation of crude glycerol and xylose into xylitol by oleaginous yeast Yarrowia lipolytica

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