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Related Concept Videos

Bioreactor Controls-III01:22

Bioreactor Controls-III

Strain improvement is a foundational strategy in industrial microbiology aimed at maximizing microbial productivity, particularly because natural isolates typically yield commercially valuable products in very low concentrations. Although optimizing the culture medium and environmental conditions can improve yields, these adjustments are inherently limited by the organism’s genetic potential. As a result, the focus shifts toward genetic modifications to enhance biosynthetic capacity. The...
Upstream Processing01:27

Upstream Processing

Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...
Overview of Protein Metabolism01:21

Overview of Protein Metabolism

Proteins are broken down into amino acids during digestion. Unlike fats and carbohydrates, which are stored for later use, proteins are not. Instead, amino acids are either used to produce ATP through oxidation or contribute to the creation of new proteins for the growth and repair of the body. Any surplus amino acids from the diet are converted into glucose or triglycerides rather than excreted.
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Production of Pharmaceuticals01:30

Production of Pharmaceuticals

Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...
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Microorganisms rely on proteins as an essential carbon and energy source, particularly in environments with limited polysaccharides or lipids. However, proteins are too large to cross the plasma membrane unaided, necessitating enzymatic degradation. Microbes secrete extracellular proteases and peptidases that hydrolyze proteins into peptides, which can then be transported across the membrane. Once inside the cell, intracellular proteases degrade these peptides into free amino acids, which...
The Central Dogma01:20

The Central Dogma

The central dogma explains the flow of genetic information from DNA nucleotides to the amino acid sequence of proteins.
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Updated: Jun 25, 2026

Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology
06:24

Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology

Published on: December 15, 2017

Cross Kingdom Metabolic Engineering Paradigm Elevating Sustainable Protein Production.

Yuanyuan Du1, Changyu Pi1, Kai Hong1

  • 1State Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|June 23, 2026
PubMed
Summary

We engineered yeast for sustainable protein production by enhancing asparagine synthetase (ASNS). This breakthrough offers a scalable solution to the global protein demand crisis, reducing reliance on traditional agriculture.

Keywords:
Pichia pastorisasparagine synthetasecarbon metabolismmethanolnitrogen assimilationsingle cell protein

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Area of Science:

  • Biotechnology
  • Metabolic Engineering
  • Synthetic Biology

Background:

  • Growing global protein demand and unsustainable agricultural practices present a dual crisis.
  • Microbial protein production offers a sustainable alternative but requires metabolic optimization.

Purpose of the Study:

  • To engineer Pichia pastoris for enhanced protein production using insights from maize nitrogen metabolism.
  • To establish a scalable microbial cell factory for sustainable single-cell protein (SCP) production.

Main Methods:

  • Overexpression of asparagine synthetase (ASNS) in Pichia pastoris.
  • Genome-scale modeling and transcriptomic analysis to understand metabolic rewiring.
  • Validation of nitrogen flux amplification and ammonia assimilation pathways.

Main Results:

  • The tri-copy ASNS strain achieved significantly higher protein titers: 62.48% crude protein, 47.86% total amino acids, and 8.05% branched-chain amino acids.
  • ASNS overexpression induced global metabolic rewiring, linking aspartate metabolism with the TCA cycle.
  • A novel nitrogen sensor-regulator circuit involving PAS_chr1-1_0158 was identified and validated.

Conclusions:

  • ASNS engineering provides a scalable blueprint for carbon-nitrogen co-optimized microbial cell factories.
  • This approach decouples sustainable SCP production from agricultural limitations.
  • The study offers a viable solution to address the global protein crisis through biotechnology.