Medium Optimization for The Production of Mycophenolic Acid by Penicillium Brevicompactum through Statistical Assessment At Shake Flask Level

Luthra, Umesh; Khadpekar, Sneha; Trivedi, Aditi

doi:10.15373/22778179/july2014/144

Cited by 1 publication

(1 citation statement)

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“…Regarding the regulation of mycophenolic acid production, several studies have indirectly addressed this topic by exploring the influence of different culture conditions on the production of this compound by fungi [59][60][61][62][63]. Furthermore, various studies have addressed the de-velopment of over-producing fungal strains through mutagenesis methods [59,61,[63][64][65]. At the molecular level, the effect of two regulators (sfk1 and pcz1) on the production of mycophenolic acid in P. roqueforti has been studied [19,20].…”

Section: Discussionmentioning

confidence: 99%

PrlaeA Affects the Production of Roquefortine C, Mycophenolic Acid, and Andrastin A in Penicillium roqueforti, but It Has Little Impact on Asexual Development

Marcano,

Montanares,

Gil-Durán

et al. 2023

JoF

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The regulation of fungal specialized metabolism is a complex process involving various regulators. Among these regulators, LaeA, a methyltransferase protein originally discovered in Aspergillus spp., plays a crucial role. Although the role of LaeA in specialized metabolism has been studied in different fungi, its function in Penicillium roqueforti remains unknown. In this study, we employed CRISPR-Cas9 technology to disrupt the laeA gene in P. roqueforti (PrlaeA) aiming to investigate its impact on the production of the specialized metabolites roquefortine C, mycophenolic acid, and andrastin A, as well as on asexual development, because they are processes that occur in the same temporal stages within the physiology of the fungus. Our results demonstrate a substantial reduction in the production of the three metabolites upon disruption of PrlaeA, suggesting a positive regulatory role of LaeA in their biosynthesis. These findings were further supported by qRT-PCR analysis, which revealed significant downregulation in the expression of genes associated with the biosynthetic gene clusters (BGCs) responsible for producing roquefortine C, mycophenolic acid, and andrastin A in the ΔPrlaeA strains compared with the wild-type P. roqueforti. Regarding asexual development, the disruption of PrlaeA led to a slight decrease in colony growth rate, while conidiation and conidial germination remained unaffected. Taken together, our results suggest that LaeA positively regulates the expression of the analyzed BGCs and the production of their corresponding metabolites in P. roqueforti, but it has little impact on asexual development.

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