{"entity": "publication", "iuid": "4ca646911b414dd48a590dbfe40c64ca", "timestamp": "2026-03-16T18:30:42.122Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4ca646911b414dd48a590dbfe40c64ca.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4ca646911b414dd48a590dbfe40c64ca"}}, "title": "Fine-tuning of p-coumaric acid synthesis to increase (2S)-naringenin production in yeast.", "authors": [{"family": "Mao", "given": "Jiwei", "initials": "J"}, {"family": "Mohedano", "given": "Marta Tous", "initials": "MT"}, {"family": "Fu", "given": "Jing", "initials": "J"}, {"family": "Li", "given": "Xiaowei", "initials": "X"}, {"family": "Liu", "given": "Quanli", "initials": "Q"}, {"family": "Nielsen", "given": "Jens", "initials": "J"}, {"family": "Siewers", "given": "Verena", "initials": "V"}, {"family": "Chen", "given": "Yun", "initials": "Y"}], "type": "journal article", "published": "2023-09-00", "journal": {"title": "Metab. Eng.", "issn": "1096-7184", "volume": "79", "pages": "192-202", "issn-l": "1096-7176"}, "abstract": "(2S)-Naringenin is a key precursor for biosynthesis of various high-value flavonoids and possesses a variety of nutritional and pharmaceutical properties on human health. Systematic optimization approaches have been employed to improve (2S)-naringenin production in different microbial hosts. However, very few studies have focused on the spatiotemporal distribution of (2S)-naringenin and the related pathway intermediate p-coumaric acid, which is an important factor for efficient production. Here, we first optimized the (2S)-naringenin biosynthetic pathway by alleviating the bottleneck downstream of p-coumaric acid and increasing malonyl-CoA supply, which improved (2S)-naringenin production but significant accumulation of p-coumaric acid still existed extracellularly. We thus established a dual dynamic control system through combining a malonyl-CoA biosensor regulator and an RNAi strategy, to autonomously control the synthesis of p-coumaric acid with the supply of malonyl-CoA. Furthermore, screening potential transporters led to identification of Pdr12 for improved (2S)-naringenin production and reduced accumulation of p-coumaric acid. Finally, a titer of 2.05 g/L (2S)-naringenin with negligible accumulation of p-coumaric acid was achieved in a fed batch fermentation. Our work highlights the importance of systematic control of pathway intermediates for efficient microbial production of plant natural products.", "doi": "10.1016/j.ymben.2023.08.003", "pmid": "37611820", "labels": {"Chalmers Mass Spectrometry Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "S1096-7176(23)00117-9"}], "notes": [], "created": "2024-01-03T13:11:34.579Z", "modified": "2024-01-03T13:11:34.583Z"}