Biosynthesis of Naringenin from p‑Coumaric Acid in Engineering Oleaginous Filamentous Fungus Mucor circinelloides

Oleaginous microorganisms have a large potential to be a cell factory to produce naringenin due to their active fatty acid anabolism offering large amounts of malonyl-CoA as the substrate for naringenin synthesis. However, only a few studies have reported the production of flavonoids in oleaginous microorganisms, e.g., Yarrowia lipolytica and Rhodosporidium toruloides. The oleaginous fungus Mucor circinelloides produces β-carotene and 15–36% of the cell dry weight of lipids. This study is the first time to engineer an oleaginous fungus, M. circinelloides, by heterologously expressing the flavonoid biosynthetic genes 4CL, CHS, and CHI to produce the recombinant product naringenin from p-coumaric acid. Limitation of this present work is that the titer of naringenin produced by recombinant strains is only 2.2 mg/L and the degradation of naringenin may exist in M. circinelloides. Moreover, the present study also provided a three gene expression platform driven by three promoters to transplant the synthesis pathway of interesting natural products into the model fungus M. circinelloides. Finally, a potential multifunctional cell factory of M. circinelloides is obtained to effectively produce naringenin and lipids.