Bacteriophage-resistant industrial fermentation strains: from the cradle to CRISPR/Cas9

Richard H Baltz1

  • 1Cognogen Biotechnology Consulting, 7636 Andora Drive, Sarasota, FL, 34238, USA. rbaltz923@gmail.com.

Insights

Bacteriophage contamination is a persistent problem in industrial fermentation. Solutions range from isolating resistant strains to using advanced CRISPR–Cas9 gene editing for robust microbial production.

Area of Science:

  • Microbiology
  • Biotechnology
  • Industrial Fermentation

Background:

  • Bacteriophage contamination and cell lysis have plagued actinomycete fermentations since the 1940s, impacting pharmaceutical production.
  • Contamination issues have also affected Escherichia coli fermentations, including those for human insulin and 1,3-propanediol production.

Purpose of the Study:

  • To review historical and modern strategies for mitigating bacteriophage contamination in industrial fermentation processes.
  • To highlight the evolution of solutions from spontaneous mutation to advanced genetic engineering and synthetic biology.

Main Methods:

  • Isolation of spontaneous phage-resistant mutants and lysogens.
  • Application of recombinant DNA technology to introduce restriction/modification systems.
  • Utilizing CRISPR–Cas9 technology to target and cleave specific phage genes.

Main Results:

  • Historically, resistant strains and genetic engineering have stabilized fermentation processes.
  • CRISPR–Cas9 effectively blocked coliphage contamination by targeting multiple phage genes.
  • These diverse methods offer broad applicability to various industrial microorganisms.

Conclusions:

  • Bacteriophage contamination remains a significant challenge in industrial biotechnology.
  • A spectrum of techniques, from classical to synthetic biology, can effectively manage phage contamination.
  • These strategies are crucial for ensuring stable and efficient microbial fermentation for diverse biotechnological applications.

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