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Published on: January 11, 2018
Metabolic engineering of capsular polysaccharides.
Asher Williams1, Robert J Linhardt1,2,3, Mattheos A G Koffas1,3
1Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, U.S.A.
Metabolic engineering transforms microbes into cellular factories for producing valuable capsular polysaccharides (CPSs). This review details strategies for engineering heparosan, chondroitin, hyaluronan, and polysialic acid for biomedical uses.
Area of Science:
- Biotechnology
- Metabolic Engineering
- Microbial Engineering
Background:
- Growing demand for sustainable and reliable sources of capsular polysaccharides (CPSs) for biomedical applications.
- Traditional sources of CPSs are often toxic, unreliable, and inconsistent in product quality.
- Metabolic engineering offers a promising alternative for producing high-value CPSs.
Purpose of the Study:
- To review strategies for the metabolic engineering of four key CPSs: heparosan, chondroitin, hyaluronan, and polysialic acid.
- To highlight the potential of engineered microorganisms as cellular factories for CPS production.
- To discuss the application of these CPSs in various biomedical fields.
Main Methods:
- Exploitation of native CPS-producing microorganisms (wild-type and engineered).
- Development of genetically engineered heterologous hosts with improved or de novo pathways.
- Application of genetic engineering techniques such as gene knockout, promoter engineering, and gene expression control.
Main Results:
- Multiple-fold improvements in CPS fermentation titers compared to wild-type strains.
- Substantial increases in productivity, reaching up to 100% in some engineered strains.
- Demonstration of engineered microorganisms as industrially competitive alternatives to traditional sources.
Conclusions:
- Metabolic engineering provides effective strategies for producing important capsular polysaccharides.
- Engineered microbial cell factories offer a sustainable, reliable, and consistent source for biomedical applications.
- Optimization of these biotechnological processes is key to industrial adoption and replacing conventional methods.
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