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One-step fermentative production of PLGA from non-food renewable resources by engineered bacteria

Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular.

Korean reserachers publisherd a new strategy to produce non-natural polymers with a broad range of material properties from carbohydrates in E. coli.

This is the strategy followed to produce PLGA by microbial fermentation directly from carbohydrates:

  1. E.coli was engineered to produce glycolate from xylose by introducing the Dahms pathway from Caulobacter crescentus.

  2. Cells were engineered to simultaneous use glucose and xylose and consequently produce D-lactic and glycolytic acids.

  3. An engineered Pct converted D-lactate and glycolate to CoA intermediates in vivo.

  4. An engineered PHaC copolymerized these CoA intermediates to PLGA.

  5. Engineered E.coli strands where then further engineered to produce a variety of PLGAs with different monomer compositions. Modulations of the monomer fractions of PLGA could produce varied polymer characteristics suitable for different applications.

In chemical synthesis, use of metal catalysts and removal of lactides and glycsolides add costs. More importantly, complete removal of metal catalysts and unreacted lactides and glycolodes is important, as PLGA intended for medical applications is in direct contact with biological fluids and tissue: this is not necessary for PLGA and copolymers produced by engineered bacteria. 

Read the full research article in Nature Biotechnology

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