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Strain improvement for fermentation and biocatalysis processes by genetic engineering technology.
1Fermentation and Biocatalysis Development, Technical Operations, Bristol-Myers Squibb Company, P.O. Box 4755, Syracuse, NY, USA. shu-jen.chiang@bms.com
Journal of Industrial Microbiology & Biotechnology
|April 28, 2004
Summary
Biotechnology tools like DNA sequencing and microarrays accelerate the engineering of secondary metabolite production. Protein engineering and DNA shuffling create novel enzymes for pharmaceutical and fine chemical synthesis.
Area of Science:
- Metabolic Engineering
- Biotechnology
- Enzyme Engineering
Background:
- Cloning of the actinorhodin biosynthetic gene cluster 20 years ago marked a milestone.
- Subsequent isolation of numerous antibiotic biosynthetic gene clusters and technological breakthroughs have enabled rational design of novel metabolites.
- Current advancements focus on optimizing secondary metabolite production.
Purpose of the Study:
- To explore the application of modern biotechnology tools in enhancing secondary metabolite production.
- To discuss the future trajectory of metabolic pathway engineering and enzyme development.
- To highlight the increasing use of biocatalysts in chemical synthesis.
Main Methods:
- High-throughput DNA sequencing and DNA microarray techniques for identifying regulatory mechanisms and monitoring gene expression.
- Polymerase chain reaction (PCR) technologies for protein engineering.
- DNA shuffling for generating enzymes with improved properties.
Main Results:
- Accelerated rational application of metabolic pathway engineering for secondary metabolite overproduction.
- Development of new enzymes with enhanced stability, substrate specificity, reaction rates, and enantioselectivity.
- Increased use of whole cells or partially purified enzymes as catalysts in pharmaceutical and fine-chemical synthesis.
Conclusions:
- Modern biotechnology tools are revolutionizing the production of secondary metabolites and the development of novel enzymes.
- These advancements are paving the way for more efficient and sustainable chemical synthesis.
- The future promises continued innovation in biocatalysis and metabolic engineering for the 21st century.