Antibiotic-free bacterial fermentation

Gen‑H has developed a proprietary antibiotic‑free plasmid maintenance system that provides a safe, efficient, and scalable alternative to traditional antibiotic‑based fermentation. This innovative approach eliminates the use of antibiotics and antibiotic resistance genes entirely while maintaining robust plasmid stability throughout fermentation.

The system is suitable for antibiotic‑free protein and enzyme production, and antibiotic‑free manufacturing of plasmid DNA. It has already been successfully implemented by an industrial customer at the 10,000‑liter scale for large‑volume protein production, demonstrating its reliability and scalability under real manufacturing conditions.

Notably, the system is highly adaptable, allowing existing strains and processes can easily be shifted to an antibiotic‑free platform.

 

Advantages of the Gen‑H Antibiotic‑Free Fermentation System

Cost‑Efficient Production

  • No antibiotic supplementation required
  • No downstream purification or analytics to verify antibiotic‑free product
  • Reduced regulatory burden and lower production costs

Improved Cellular Performance

  • Eliminating antibiotic resistance markers reduces metabolic stress
  • Host cells can allocate more resources to product formation
  • Often results in higher productivity and improved yield

Safe and Antibiotic‑Free by Design

  • No antibiotics present in the fermentation process
  • No risk of antibiotic carryover into final products
  • No antibiotic resistance genes in the strain or plasmid

Reduced Risk of Resistance Development

  • Absence of resistance markers prevents horizontal transfer of antibiotic‑resistance genes
  • Supports antibiotic stewardship and sustainable bioprocessing

Flexible and Highly Compatible

  • One strain can be paired with multiple production plasmids—no helper plasmids required
  • Compatible with all common strain backgrounds, media formulations, temperatures, and expression systems
  • Easily integrated into existing production workflows

Adaptable to Existing Processes

  • Current strains and fermentation processes can be converted to the Gen‑H antibiotic‑free system with minimal re‑engineering
  • Offers a smooth transition from antibiotic‑based to antibiotic‑free plasmid maintenance

Technology Overview

The Gen‑H system is fully independent of antibiotics:
no antibiotics in the culture, no resistance genes in the cells.

This patented technology is based on conditional complementation. An essential endogenous gene in the production strain is replaced by an inducible genomic copy. In the absence of the inducer, cell viability depends on a production plasmid that provides a constitutively expressed copy of the essential gene. This ensures stable plasmid maintenance without antibiotic pressure.

Crucially, expression of the genomic copy can be induced, enabling growth without a plasmid. This allows rapid introduction of new plasmids without labor‑intensive strain modifications or the use of helper plasmids—offering exceptional flexibility for strain development and process optimization.

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Gen-H Genetic Engineering Heidelberg GmbH
Im Neuenheimer Feld 584
69120 Heidelberg