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Bioprocess

About: Bioprocess is a research topic. Over the lifetime, 2219 publications have been published within this topic receiving 50972 citations.


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Journal ArticleDOI
TL;DR: In this article, high value-added products and biogas were obtained via an innovative two-stage anaerobic bioprocess from microalgae biomass, and the results showed that operational conditions imposed mediated a microbial specialization that maximized product output.

19 citations

Journal ArticleDOI
12 Apr 2019
TL;DR: This review presents a systematic and detailed summary of the contemporary metabolic engineering approaches employed for l-tryptophan production and the metabolic engineering modification of carbon source uptake, by-product formation, key regulatory factors, and the polyhydroxybutyrate biosynthesis pathway in l-Tryptophans biosynthesis are discussed.
Abstract: L-tryptophan is an essential aromatic amino acid that has been widely used in medicine, food, and animal feed. Microbial biosynthesis of L-tryptophan through metabolic engineering approaches represents a sustainable, cost-effective, and environmentally friendly route compared to chemical synthesis. In particular, metabolic pathway engineering allows enhanced product titers by inactivating/blocking the competing pathways, increasing the intracellular level of essential precursors, and overexpressing rate-limiting enzymatic steps. Based on the route of the L-tryptophan biosynthesis pathway, this review presents a systematic and detailed summary of the contemporary metabolic engineering approaches employed for L-tryptophan production. In addition to the engineering of the L-tryptophan biosynthesis pathway, the metabolic engineering modification of carbon source uptake, by-product formation, key regulatory factors, and the polyhydroxybutyrate biosynthesis pathway in L-tryptophan biosynthesis are discussed. Moreover, fermentation bioprocess optimization strategies used for L-tryptophan overproduction are also delineated. Towards the end, the review is wrapped up with the concluding remarks, and future strategies are outlined for the development of a high L-tryptophan production strain.

19 citations

Posted ContentDOI
09 Jun 2020
TL;DR: Critical parameters affecting the productivity of the engineered strain were identified across a range of scales, providing a foundation for the development of robust integrated bioprocess control systems.
Abstract: Taxadien-5α-hydroxylase and taxadien-5α-ol O-acetyltransferase catalyse the oxidation of taxadiene to taxadien-5α-ol and subsequent acetylation to taxadien-5α-yl-acetate in the biosynthesis of the blockbuster anti-cancer drug, paclitaxel (Taxol). Despite decades of research, the promiscuous and multispecific CYP725A4 enzyme remains a major bottleneck in microbial biosynthetic pathway development. In this study, an interdisciplinary approach was applied for the construction and optimisation of the early pathway in Saccharomyces cerevisiae, across a range of bioreactor scales. High-throughput microscale optimisation enhanced total oxygenated taxane titre to 39.0±5.7 mg/L and total taxane product titres were comparable at micro and mini-bioreactor scale at 95.4±18.0 and 98.9 mg/L, respectively. The introduction of pH control successfully mitigated a reduction of oxygenated taxane production, enhancing the potential taxadien-5α-ol isomer titre to 19.2 mg/L, comparable to the 23.8±3.7 mg/L achieved at microscale. A combination of bioprocess optimisation and increased GC-MS resolution at 1L bioreactor scale facilitated taxadien-5α-yl-acetate detection with a final titre of 3.7 mg/L. Total oxygenated taxane titres were improved 2.7-fold at this scale to 78 mg/L, the highest reported titre in yeast. Critical parameters affecting the productivity of the engineered strain were identified across a range of scales, providing a foundation for the development of robust integrated bioprocess control systems.

19 citations

Journal ArticleDOI
TL;DR: Near infrared spectroscopy was used to monitor an industrial bioprocess for the production of the antibiotic, tylosin, using a segmented modelling approach and the standard error of prediction of the segmented models was less and the correlation highest in the 50–100 h range, suggesting that data segmentation is potentially a useful method of accommodating the impact of the pronounced matrix changes.
Abstract: Near infrared spectroscopy (NIRS) was used to monitor an industrial bioprocess for the production of the antibiotic, tylosin, using a segmented modelling approach. Models were built over the entire time course of the fermentation from 0 to 150 h, and also in two distinct phases or segments of the bioprocess from 50 to 100 h (synthetic phase) and from 100 to 150 h (stationary phase). All models were validated externally and the performance of the full range and segmented models compared. The standard error of prediction (SEP) of the segmented models was less in both 50–100 h and 100–150 h and the correlation highest in the 50–100 h range. This would suggest that data segmentation is potentially a useful method of accommodating the impact of the pronounced matrix changes which occur in some bioprocesses in NIRS models for key analytes. While there are many reports on bioprocess monitoring using NIRS, there have been no previous studies on the use of segmented NIR models within a bioprocess as a means of accommodating matrix change.

19 citations

Journal ArticleDOI
TL;DR: Intracellular metabolic profiles of the CHO fed‐batch culture were shown to be consistent with scale and thus demonstrate metabolomic profiling as an informative method to gain physiological insight into the cell culture states during bioprocess regardless of scale.
Abstract: Established bioprocess monitoring is based on quick and reliable methods, including cell count and viability measurement, extracellular metabolite measurement, and the measurement of physicochemical qualities of the cultivation medium. These methods are sufficient for monitoring of process performance, but rarely give insight into the actual physiological states of the cell culture. However, understanding of the latter is essential for optimization of bioprocess development. Our study used LC-MS metabolomics as a tool for additional resolution of bioprocess monitoring and was designed at three bioreactors scales (10 L, 100 L, and 1,000 L) to gain insight into the basal metabolic states of the Chinese hamster ovary (CHO) cell culture during fed-batch. Metabolites characteristics of the four growth stages (early and late exponential phase, stationary phase, and the phase of decline) were identified by multivariate analysis. Enriched metabolic pathways were then established for each growth phase using the CHO metabolic network model. Biomass generation and nucleotide synthesis were enriched in early exponential phase, followed by increased protein production and imbalanced glutathione metabolism in late exponential phase. Glycolysis became downregulated in stationary phase and amino-acid metabolism increased. Phase of culture decline resulted in rise of oxidized glutathione and fatty acid concentrations. Intracellular metabolic profiles of the CHO fed-batch culture were also shown to be consistent with scale and thus demonstrate metabolomic profiling as an informative method to gain physiological insight into the cell culture states during bioprocess regardless of scale.

19 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023331
2022785
2021165
2020153
2019159
2018127