Increased production of ganoderic acids by overexpression of homologous farnesyl diphosphate synthase and kinetic modeling of ganoderic acid production in Ganoderma lucidum

BackgroundGanoderic acids (GAs), derived from the medicinal mushroom Ganoderma lucidum, possess anticancer and other important pharmacological activities. To improve production of GAs, a homologous farnesyl diphosphate synthase (FPS) gene was overexpressed in G. lucidum. Moreover, the influence of FPS gene overexpression on GA production was investigated by developing the corresponding mathematical models.ResultsThe maximum levels of total GAs and individual GAs (GA-T, GA-S, and GA-Me) in the transgenic strain were 2.76mg/100mg dry weight (DW), 412, 21 +/- 5, and 28 +/- 1g/100mg DW, respectively, which were increased by 2.28-, 2.27-, 2.62-, and 2.80-folds compared with those in the control. Transcription levels of squalene synthase (SQS) and lanosterol synthase (LS) genes during GA biosynthesis were upregulated by 2.28- and 1.73-folds, respectively, in the transgenic G. lucidum. In addition, the developed unstructured models had a satisfactory fit for the process of GA production in submerged cultures of G. lucidum. Analysis of the kinetic process showed that FPS gene overexpression had a stronger positive impact on GA production compared with its influence on cell growth. Also, FPS gene overexpression led to a higher non-growth-associated-constant (1.151) over the growth-associated-constant (0.026) in the developed models.Conclusions p id= Par FPS gene overexpression is an effective strategy to improve the production of GAs in G. lucidum. The developed mathematical models are useful for developing a better GA production process in future large-scale bioreactors.