Effect of fatty acids on intracellular pneumocandin B₀ storage in the fermentation of Glarea lozoyensis

The natural product pneumocandin B₀ is the precursor of the antifungal drug caspofungin. To explore the relationship between pneumocandin B₀ and oil. We found that the addition of 1 g/L of oil to the fermentation medium is more conducive to the production of pneumocandin B₀. The metabolic reaction mechanism was explored using different fatty acids and the results showed that stearic acid and acetic acid increased the total production of pneumocandin B₀ by 22.98% and 9.08%, respectively, as well as increasing the content of intracellular lipid droplets. We also analyzed gene expression and pathway differences between the two different fatty acids using transcriptome analyses. The addition of both acetic acid and stearic acid promoted an active pentose phosphate pathway, providing cells with higher intracellular reducing power. We found that the addition of fatty acids can lead to lipid accumulation, and lipid droplets can sequester lipophilic secondary metabolites such as pneumocandin B₀ to reduce cell damage. These results provide novel insights into the relationship between pneumocandin B₀ biosynthesis and fatty acids in G. lozoyensis. In addition, this study provides important genetic information for improving the yield of pneumocandin B₀ through a strategy of metabolic engineering in the future. Graphical Abstract: [Figure not available: see fulltext.].