A research group has successfully engineered a microbial strain that can produce aromatic polyester effectively through systems metabolic engineering.
Among the many environmentally friendly plastics, polyhydroxyalkanoates (PHA) are notable for their superior biodegradability and biocompatibility. These materials can naturally break down in soil and oceanic environments, making them suitable for uses like food packaging and medical devices. Nevertheless, the natural PHAs produced so far struggle to meet certain physical benchmarks, such as strength and heat resistance, which has restricted their commercial viability due to insufficient production yields. To address these issues, researchers at KAIST have recently unveiled a technology that could significantly help tackle the plastic pollution crisis.
On August 26th, KAIST, under the leadership of President Kwang-Hyung Lee, announced that a research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering, along with Dr. Youngjoon Lee and master’s student Minju Kang, has successfully created a microbial strain that produces aromatic polyester* efficiently via systems metabolic engineering.
Aromatic polyester: This refers to a type of polymer that features aromatic compounds (which are carbon ring structures like benzene) bonded with ester links.
In this project, the research team utilized metabolic engineering techniques to boost the metabolic flow within the biosynthetic pathway for the aromatic monomer phenyllactate (PhLA) in E. coli. By fine-tuning the metabolic pathways, they were able to elevate the ratio of polymer accumulated within the cells and employed computer modeling to forecast the structure of PHA synthase, enhancing the enzyme according to its structure-function relationship.
The subsequent optimization of fermentation led the team to achieve the world’s highest concentration (12.3±0.1 g/L) for the efficient production of poly(PhLA). They successfully created polyester using a 30L scale fed-batch fermentation, showcasing the potential for industrial-level production. The resultant aromatic polyesters exhibited improved thermal and mechanical properties and showed promise as carriers for drug delivery.
The research team revealed that an external phasin protein* is critical for boosting the intracellular polymer accumulation ratio, which is vital for the economic viability and efficiency of non-natural PHA production. They fine-tuned PHA synthase through an intelligent enzyme design strategy that involved predicting the three-dimensional structure of the enzyme using homology modeling—this method estimates the structure of a new protein based on similar existing proteins—followed by simulations for molecular docking (to foresee how effectively a monomer can bond with an enzyme) and molecular dynamics (to observe how molecules move and interact over time) to create a mutant enzyme with enhanced efficiency for monomer polymerization.
Exogenous phasin protein: Phasin is a type of protein that is associated with PHA production, interacting within the cytoplasmic environment and the surface of PHA granules, playing a role in the accumulation of polymer and regulating the granules’ number and size. This study selected genes encoding phasin proteins from various natural PHA-producing microorganisms to introduce them.
Dr. Youngjoon Lee, the co-first author of the study, stated, “The importance of our findings lies in achieving the highest concentration of microbial-based aromatic polyester production with eco-friendly materials and methods. This technology is anticipated to be pivotal in combating environmental issues associated with plastic.” Distinguished Professor Sang Yup Lee emphasized, “This research presents several strategies for the efficient production of valuable polymers through systems metabolic engineering, and it is expected to significantly aid in addressing climate change challenges, particularly the ongoing plastic crisis.”
The findings from this research were published on August 21st in Trends in Biotechnology, a journal from Cell, an international academic publication.
