Journal Article

Microbial production of an aromatic homopolyester

Yang, Jung Eun, Lee, Youngjoon, Lee, Sang Yup, Kang, Minju, Choi, So Young, Jang, Woo Dae

2024

Overview

A homo-aromatic polyester was produced from glucose for the first time.Aromatic polyhydroxyalkanoate (PHA) was produced to the highest titer yet achieved.3D model-based rational engineering of PHA synthase was used to enhance aromatic PHA production.Polymer production was enhanced by utilizing heterologous phasins.Pilot-scale fermentative production of aromatic PHAs was successful. We report the development of a metabolically engineered bacterium for the fermentative production of polyesters containing aromatic side chains, serving as sustainable alternatives to petroleum-based plastics. A metabolic pathway was constructed in an Escherichia coli strain to produce poly[d-phenyllactate(PhLA)], followed by three strategies to enhance polymer production. First, polyhydroxyalkanoate (PHA) granule-associated proteins (phasins) were introduced to increase the polymer accumulation. Next, metabolic engineering was performed to redirect the metabolic flux toward PhLA. Furthermore, PHA synthase was engineered based on in silico simulation results to enhance the polymerization of PhLA. The final strain was capable of producing 12.3 g/l of poly(PhLA), marking it the first bio-based process for producing an aromatic homopolyester. Additional heterologous gene introductions led to the high level production of poly(3-hydroxybutyrate-co-11.7 mol% PhLA) copolymer (61.4 g/l). The strategies described here will be useful for the bio-based production of aromatic polyesters from renewable resources. Graphical abstract [Display omitted] The production of polyhydroxyalkanoates (PHAs) containing aromatic repeating units has been studied for decades, but has yet to be demonstrated in large-scale fermentation. This study reports the successful production of aromatic polyesters from glucose in high titers that was performed both in lab-scale (5 l) and pilot-scale (30 l) fermenters. Therefore, the current Technology Readiness Level (TRL) of this technology lies between 4 and 5. To advance this technology for industrialization, demonstration in industry-scale fermenters and the development of large-scale downstream processes will be necessary. Nevertheless, given the ongoing development of various fermentation technologies and purification processes for other PHAs, we anticipate that the industrialization of aromatic PHAs is feasible, potentially replacing petroleum-based aromatic polymers for use as commodity, engineering, and biomedical plastics. Lee et al. report the fermentative production of aromatic polyesters, which can serve as sustainable alternatives to petroleum-based plastics. This represents the first instance of homo-aromatic polyester production using glucose. Further pathway engineering facilitated the production of poly(3-hydroxybutyrate-co-d-phenyllactate), achieving the highest titer of aromatic polyester reported using microorganisms thus far.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Acids / Acyltransferases - genetics / Acyltransferases - metabolism / aromatic polyesters / biodegradable plastics / Carbon / Coliforms / Copolymers / Dehydrogenases / E coli / Engineering / enzyme engineering / Enzymes / Escherichia coli / Escherichia coli - genetics / Escherichia coli - metabolism / Fermentation / Genomes / Glucose / Internal Medicine / Lactates / Metabolic engineering / Metabolic Engineering - methods / Metabolic flux / Metabolic Networks and Pathways - genetics / Metabolic pathways / Metabolism / Microorganisms / non-natural polyesters / phasin / phenyllactate / Plasmids / Plastics / Polyester resins / Polyesters / Polyesters - metabolism / Polyethylene terephthalate / Polyhydroxyalkanoates / Polyhydroxyalkanoates - biosynthesis / Polyhydroxyalkanoates - genetics / Polyhydroxyalkanoates - metabolism / Polyhydroxyalkanoic acid / Polymerization / Polymers / Proteins / Renewable resources / Sustainable yield / systems metabolic engineering