Fed-batch high-cell-density fermentation strategies for <i>Pichia pastoris</i> growth and production

Liu, Wan-Cang; Inwood, Sarah; Gong, Ting; Sharma, Ashish K.; Yu, Liyan; Zhu, Ping

doi:10.1080/07388551.2018.1554620

Cited by 87 publications

(55 citation statements)

References 125 publications

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“…Afterward, the fed‐batch operation was started by using glycerol as limiting carbon nutrient until reaching optimal biomass content, i.e. by the depletion of glycerol repressing P AOX1 for methanol utilization by recombinant P. pastoris . In the third stage, the methanol transition phase, methanol was added gradually to the fermenter so that P. pastoris was being adapted to methanol as a new carbon source .…”

Section: Methodsmentioning

confidence: 99%

“…Despite the technical and safety constraints related to methanol, P. pastoris with P AOX1 is still the most well‐characterized and widely studied strain; it has already been used as an industrial strain for commercial‐scale production of recombinant hepatitis B vaccine (HBV) for more than 20 years . In this specific industrial strain, hepatitis B surface antigens (HBsAgs), the main component of HBV, are produced intracellularly and then form virus‐like particles (VLPs) during the downstream process .…”

Section: Introductionmentioning

confidence: 97%

“…For P. pastoris with P AOX1 , various methanol feeding strategies have been proposed. These strategies are mainly performed by controlling one of the important key factors, including the specific growth rate ( μ ‐stat), the dissolved oxygen (DO‐stat), the methanol concentration (methanol‐stat), the biomass (biomass‐stat) and limited temperature, reviewed extensively in many previous studies . Among the mentioned feeding strategies, μ ‐stat feeding under the optimal value of specific growth rate has shown promising results in terms of process efficiency …”

Section: Introductionmentioning

confidence: 99%

“…14 Apart from natural promoters, since the last decade, there has also been growing interest in using other synthetic-engineered promoters to increase the production rate without the major challenges related to P AOX1. 15,16 PFLD1, ICL1 PEX8, YPT1, PCAT1, PPMP20, PDAS2 and NPS are some of the highly regulated promoters with a high production level of heterologous proteins which were extensively described by Vogl et al [15][16][17] Despite the technical and safety constraints related to methanol, P. pastoris with P AOX1 is still the most well-characterized and widely studied strain; [18][19][20][21] it has already been used as an industrial strain for commercial-scale production of recombinant hepatitis B vaccine (HBV) for more than 20 years. [22][23][24] In this specific industrial strain, hepatitis B surface antigens (HBsAgs), the main component of HBV, are produced intracellularly and then form virus-like particles (VLPs) during the downstream process.…”

Section: Introductionmentioning

confidence: 99%

“…These strategies are mainly performed by controlling one of the important key factors, including the specific growth rate ( -stat), the dissolved oxygen (DO-stat), the methanol concentration (methanol-stat), the biomass (biomass-stat) and limited temperature, reviewed extensively in many previous studies. 6,19,34 Among the mentioned feeding strategies, -stat feeding under the optimal value of specific growth rate has shown promising results in terms of process efficiency. 6,35 For the industrial strain of recombinant P. pastoris with P AOX1 producing intracellular HBsAg, -stat feeding had already been established as one of the suitable methanol feeding strategies.…”

Section: Introductionmentioning

confidence: 99%

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Comparative study of μ‐stat methanol feeding control in fed‐batch fermentation of Pichia pastoris producing HBsAg: an open‐loop control versus recurrent artificial neural network‐based feedback control

Beiroti

Hosseini

Aghasadeghi

et al. 2019

J of Chemical Tech & Biotech

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BACKGROUND In recent decades, artificial neural network (ANN) has been shown to be a robust and promising tool in monitoring and controlling bioprocess systems. In a previous study, the authors designed a highly accurate and precise recurrent neural network (RNN) for predicting the biomass amount of recombinant Pichia pastoris Mut+ producing intracellular hepatitis B surface antigen (HBsAg) during fed‐batch methanol fermentation. In the current work, the aim was to compare the production efficiency of HBsAg between conventional predefined μ‐stat methanol feeding control (open‐loop control) – already established in large‐scale production – and methanol feeding based on a μ‐stat feedback control system using RNN. For this purpose, for each methanol feeding strategy, bench‐scale, fed‐batch fermentation processes were carried out twice. RESULTS According to the results, in contrast to the established μ‐stat predefined feeding strategy (open‐loop), the deviation of specific growth rate and biomass in μ‐stat feedback control based on RNN was negligible. Also, in the suggested methanol feeding control strategy, the HBsAg titer, specific productivity and yield between the performed fed‐batch fermentations – unlike the conventional method – were approximately identical, with average values of 110.8 μg mL−1, 1.52 μg g−1 dry biomass and 0.34 μg g−1 MeOH respectively. CONCLUSION Comparing the biomass growth pattern and HBsAg production efficiency with the conventional μ‐stat predefined feeding in open‐loop control, the new proposed feeding control system illustrated significantly high process efficiency. This reliable control system based on ANN can have many applications in the biopharmaceutical industry for the control of process key parameters as well as for enhancing process efficiency. © 2019 Society of Chemical Industry

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Comparative study of μ‐stat methanol feeding control in fed‐batch fermentation of Pichia pastoris producing HBsAg: an open‐loop control versus recurrent artificial neural network‐based feedback control

Beiroti

Hosseini

Aghasadeghi

et al. 2019

J of Chemical Tech & Biotech

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Preparation of Recombinant Membrane Proteins from Pichia pastoris for Molecular Investigations

et al. 2020

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Pichia pastoris is a eukaryotic microorganism reputed for its ability to mass-produce recombinant proteins, including integral membrane proteins (IMPs), for various applications. This chapter details a series of protocols that progress towards the production of IMPs, their extraction and purification in presence of detergents, and their eventual reconstitution in lipid nanoparticles. These P. pastoris-oriented basic procedures can be further optimized in order to deliver IMP samples compatible with a number of structural and/or functional investigations at the molecular level. Each protocol provides a number of general guidelines, technical hints and specific recommendations, and is illustrated with case studies corresponding to several representative mammalian IMPs.

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Mini-Bioreactor Platform for Membrane Protein Production in Komagataella pastoris

Barroca-Ferreira

Maia

Passarinha

2023

Methods in Molecular Biology

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Fed-batch high-cell-density fermentation strategies for Pichia pastoris growth and production

Cited by 87 publications

References 125 publications

Comparative study of μ‐stat methanol feeding control in fed‐batch fermentation of Pichia pastoris producing HBsAg: an open‐loop control versus recurrent artificial neural network‐based feedback control

Comparative study of μ‐stat methanol feeding control in fed‐batch fermentation of Pichia pastoris producing HBsAg: an open‐loop control versus recurrent artificial neural network‐based feedback control

Preparation of Recombinant Membrane Proteins from Pichia pastoris for Molecular Investigations

Mini-Bioreactor Platform for Membrane Protein Production in Komagataella pastoris

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