Work

Engineering Yarrowia lipolytica as a yeast cell factory for the de novo production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate)

Year: 2025

Type: article

Abstract: The oleaginous yeast Yarrowia lipolytica presents a promising chassis for the production of biodegradable plastic polyhydroxyalkanoates (PHAs) due to its advantages in precursor supply capabilities and cost-effective substrate utilization. However, Y. lipolytica has primarily been engineered for the synthesis of homopolymeric PHAs, such as poly(3-hydroxybutyrate) (P3HB), which have limited material properties and application potential. In this study, the succinate dehydrogenase-deficient Y. lipolytica strains were utilized as hosts for the de novo biosynthesis of copolymer poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB). By employing a strategy of subcellular partitioning, poly(4-hydroxybutyrate) (P4HB) was synthesized in the cytoplasm using 4-hydrobutyrate (4HB) derived from mitochondrial sources as a monomer. We then introduced the biosynthetic pathway for 3-hydroxybutyryl-CoA to facilitate P34HB accumulation. Importantly, the ratio of 4HB monomer in P34HB could be adjusted from 9.17 mol% to 45.26 mol% by varying medium components and carbon sources. Under fed-batch fermentation conditions in a 5 L bioreactor, the engineered strain achieved a P34HB titer of 18.61 g/L representing 19.18% of cell dry weight (CDW). This study not only demonstrates the potential of Y. lipolytica for P34HB synthesis, but also expands the monomer pool available for PHAs in yeast cell factories.

Source: Synthetic and Systems Biotechnology

DOI: 10.1016/j.synbio.2025.09.002

Authors: Jinming Liu, Jia Yan, Zhiyong Cui, Qingsheng Qi

Institutions: Shandong University, State Key Laboratory of Microbial Technology

Language: English

Topic: biodegradable polymer synthesis and properties

Subfield: Biomaterials

Field: Materials Science

Domain: Physical Sciences

SDG: Responsible consumption and production

Open Access status: gold

Estimated APC paid: $1,500