Optimization of medium compositions and X-ray irradiation to enhance monacolin K production by Monascus purpureus in submerged fermentation

The secondary metabolite Monacolin K (MK), derived from Monascus, exhibits potential lipid-lowering and anti-tumor effects. In this study, a mutant strain M. purpureus M400-6 was generated through X-ray treatment, resulting in an average MK production of 181.97 mg/L (a 54.20% increase compared to the parent strain M. purpureus M1) over five successive generations. Furthermore, optimization of medium compositions using response surface methodology led to a further enhancement in MK production by the mutant strain to 266.63 mg/L. Moreover, based on the outcomes of single-factor experiments, the addition of L-citrulline demonstrated a significantly higher level of enhancement in MK production. Therefore, a comparative transcriptome analysis was conducted to unveil the impact of L-citrulline on MK biosynthesis in M. purpureus. The data revealed a significant upregulation of glycolysis pathways, while oxidative phosphorylation including the TCA cycle and the electron transport chain, exhibited significant downregulation. Furthermore, the metabolisms of serine, glycine, threonine, alanine, aspartic acid and glutamate were found to be significantly disturbed. Additionally, the expressions of MPs and MK biosynthetic gene cluster showed a significant downregulation and upregulation respectively. Overall, these findings provide insights into enhancing MK production in submerged fermentation and elucidate the impact of L-citrulline on secondary metabolism.