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Synthetic biology is an interdisciplinary science that involves using principles from disciplines such as engineering, molecular biology, cell biology, and systems biology. It involves remodeling existing organisms from nature or constructing completely new synthetic organisms for applications such as protein or enzyme production, bioremediation, value-added macromolecule production, and the addition of desirable traits to crops, to name a few.
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Bioreactors are engineered vessels designed to cultivate microorganisms under controlled conditions for industrial bioprocessing. They maintain sterility and allow precise regulation of pH, temperature, oxygen, and nutrient levels to optimize microbial growth and metabolite production. Bioreactors range from small laboratory units of 1 liter to industrial systems holding up to 500,000 liters, though only about 75% of their volume is actively used for fermentation. The remaining headspace...
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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...
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Growth media provide essential nutrients that support cell growth and metabolism, thereby enhancing the yield of valuable products such as enzymes, antibiotics, and biomass. Designing an effective growth medium involves balancing all components to prevent nutrient limitations or toxic excesses, both of which can impair growth and reduce product yields.Composition of a Typical Growth MediumA typical growth medium contains carbon and nitrogen sources, salts, vitamins, trace elements, and...
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The scale-up of microbial fermentation processes is essential in industrial biotechnology, allowing the transition from laboratory-scale experiments to commercial-scale production while aiming to maintain product yield and quality. This process requires meticulous adjustment of equipment design, process parameters, and contamination control strategies to accommodate increasing culture volumes.At the laboratory scale, cultures are typically maintained in 1 to 10-liter glass or autoclavable...
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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...
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A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics
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AutoBioTech─A Versatile Biofoundry for Automated Strain Engineering.

Tobias Michael Rosch1, Julia Tenhaef1, Tim Stoltmann1

  • 1Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, D-52425 Jülich, Germany.

ACS Synthetic Biology
|July 8, 2024
PubMed
Summary
This summary is machine-generated.

The AutoBioTech platform offers a fully automated solution for microbial strain engineering, accelerating the development of novel producer strains for renewable alternatives. This system enhances biofoundry capabilities for both Gram-negative and Gram-positive bacteria.

Keywords:
CRISPR/Cas9Corynebacterium glutamicumEscherichia coliautomationmodular cloning

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Area of Science:

  • Biotechnology and synthetic biology
  • Microbial engineering
  • Automation in life sciences

Background:

  • The shift towards renewable resources necessitates advanced microbial production strains.
  • Manual microbial engineering methods are insufficient for the growing demand.
  • Biofoundries are emerging to address these challenges through automation.

Purpose of the Study:

  • To introduce the AutoBioTech platform, a fully automated system for microbial strain construction.
  • To demonstrate the platform's capability for automated genome editing and transformation.
  • To enable high-throughput strain engineering for both Gram-negative and Gram-positive bacteria.

Main Methods:

  • Development of a 14-device automated laboratory system (AutoBioTech).
  • Implementation of modular workflows for automated microbial transformations.
  • Integration of a CRISPR/Cas9 toolbox for automated genome editing.
  • Establishment of automated transformation protocols for *Escherichia coli* and *Corynebacterium glutamicum*.

Main Results:

  • The AutoBioTech platform successfully performed automated strain construction without human intervention.
  • Automated transformation of *E. coli* using modular cloning and CRISPR/Cas9 was achieved.
  • Robust automated transformation of *C. glutamicum* was established via electroporation.
  • The platform demonstrated versatility and seamless transitions between modular workflows.

Conclusions:

  • The AutoBioTech platform significantly accelerates microbial strain engineering.
  • Its modularity and automation support both Gram-negative and Gram-positive bacteria.
  • This system advances the capacity of biofoundries for developing novel microbial producers.