Biomedical polymers produced from gut microbes

Scientists have employed gut microbes to create non-natural polymers commonly used in drug delivery and making biomedical devices, an advance that could help produce plastics in an environment-friendly and sustainable manner.
Renewable non-food biomass could potentially replace petrochemical raw materials to produce energy sources, useful chemicals or petroleum-based products such as plastics, lubricants, paints, fertilisers and vitamin capsules.
The researchers headed by Sang Yup Lee from the Korea Advanced Institute of Science and Technology (KAIST) developed a microorganism that can produce diverse non-natural polymers and succeeded in synthesising poly(lactate-co-glycolate) (PLGA), a copolymer of two different polymer monomers, lactic and glycolic acid.

PLGA is biodegradable, biocompatible, and non-toxic, and has been widely used in biomedical and therapeutic applications such as surgical sutures, prosthetic devices, drug delivery, and tissue engineering.
The researchers designed a metabolic pathway for the biosynthesis of PLGA through microbial fermentation directly from carbohydrates in Escherichia coli (E coli) strains.
The bio-based synthetic process could substitute for the existing chemical production that involves the preparation and purification of precursors, chemical polymerisation processes, and the elimination of metal catalysts.

Researchers performed in silico genome-scale metabolic simulations of the E coli cell to predict and analyse changes in the metabolic fluxes of cells which are caused by the introduction of external metabolic pathways.

Based on these results, genes are manipulated to optimise metabolic fluxes by eliminating the genes responsible for byproducts formation and enhancing the expression levels of certain genes, thereby achieving the effective production of target polymers as well as stimulating cell growth.
The team utilised the structural basis of broad substrate specificity of the key synthesising enzyme, PHA synthase, to incorporate various co-monomers with main and side chains of different lengths.
These monomers were produced inside the cell by metabolic engineering, and then copolymerised to improve the material properties of PLGA.
The team employed a systems metabolic engineering application which, according to the researchers, is the first successful example of biological production of PGLA and several novel copolymers from renewable biomass by one-step direct fermentation of metabolically engineered E coli.

"We presented important findings that non-natural polymers, such as PLGA which is commonly used for drug delivery or biomedical devices, were produced by a metabolically engineered gut bacterium," Lee said.
The research was published in the journal Nature Biotechnology.