2A peptides enable simplified discovery and heterologous production of fungal bioactive metabolites in Yarrowia lipolytica
Mihaela Bejenari, Mikkel Rank Nielsen, Jens Laurids Sørensen
TL;DR
Researchers used 2A peptides to simplify the production of fungal bioactive compounds in Yarrowia lipolytica, improving the efficiency of heterologous expression.
Contribution
The study introduces non-canonical 2A peptides to enhance polycistronic expression in Y. lipolytica for fungal metabolite biosynthesis.
Findings
The PNPV2A1 peptide enabled m-cresol production in Y. lipolytica at 306 mg/L.
Non-canonical 2A peptides outperformed some canonical ones in bicistronic setups.
The study expands the toolkit for polycistronic expression in Y. lipolytica.
Abstract
Filamentous fungi are a valuable source of bioactive secondary metabolites (SMs), the discovery of which is hindered by the challenges in cultivation and metabolic engineering. Yarrowia lipolytica emerges as a promising heterologous host for SMs, yet efficient expression of multigene biosynthetic clusters remains a bottleneck due to limited polycistronic expression strategies. In this study, we developed bicistronic TdTomato-2A-hrGFP reporters to compare the efficiency of various viral 2A peptides in Y. lipolytica and identify the most effective 2A sequences. Using the PNPV2A1 peptide in a bicistronic setup, we reconstructed and validated the partial Aspergillus hancockii putative patulin pathway, producing m-cresol in Y. lipolytica and achieving a titer of 306 mg/L in comparison to 418 mg/L in the monocistronic setup. Our work expands the polycistronic toolkit for Y. lipolytica, beyond…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsMicrobial Metabolic Engineering and Bioproduction · Microbial Natural Products and Biosynthesis · Enzyme Catalysis and Immobilization