Improved β-carotene synthesis in fas-knockout Mucor circinelloides strains

Previously, engineered strains lacking fatty acid synthase ( fas ) genes ( fas1 or fas2 ) were constructed in the oleaginous fungus Mucor circinelloides WJ11. The deletion of the fas gene not only increased lipid content but also enhanced the accumulation of β-carotene. This study aimed to investigate the impact of single-gene deletion of fas1 and fas2 on β-carotene synthesis in M. circinelloides . When compared with the control strain, the β-carotene contents in fas -knockout strains were increased by 1.6-fold for Mc- fas1 Δ and 3.5-fold for Mc- fas2 Δ, respectively. Meanwhile, the transcriptional levels of 3-hydroxy-3-methylglutaryl-CoA synthase ( hmgS ), 3-hydroxy-3-methylglutaryl-CoA reductase ( hmgR ), phytoene dehydrogenase ( carB ) and phytoene synthase/lycopene cyclase ( carRP ) involved in mevalonate pathway were significantly increased in fas -knockout strains. The yield of lipid and β-carotene in fas -knockout strains were significantly higher than those of the control strain. It was speculated that the deletion of the fas genes might initiate potent compensatory regulation to accelerate acetyl-CoA production, which supplies abundant precursors for lipid and carotenoid biosynthesis in M. circinelloides . To our knowledge, this is the first report uncovering the functional linkage between fas genes and β-carotene synthesis in this oleaginous fungus.