Dataset Information

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

ABSTRACT:

Background

Ganoderic 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.

Results

The maximum levels of total GAs and individual GAs (GA-T, GA-S, and GA-Me) in the transgenic strain were 2.76 mg/100 mg dry weight (DW), 41 ± 2, 21 ± 5, and 28 ± 1 μg/100 mg 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 β (1.151) over the growth-associated-constant α (0.026) in the developed models.

Conclusions

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.

SUBMITTER: Fei Y

PROVIDER: S-EPMC6599323 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Fei Yu Y Li Na N Zhang De-Huai DH Xu Jun-Wei JW

Microbial cell factories 20190628 1

<h4>Background</h4>Ganoderic 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.<h4>Results</h4>The maximum levels of total GAs and individual GAs (GA-T, GA-S, an ...[more]

PMID: 31253150

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Project description:BackgroundGanoderic acids (GAs), recognized as significant triterpenoid bioactive components in Ganoderma lucidum, exhibit a broad spectrum of pharmacological activities, including immunomodulation, anti-cancer, and anti-aging properties. Despite their significant pharmacological potential, the low yield of GAs from natural sources has emerged as a critical bottleneck hindering their broader application in the pharmaceutical and health care industries. Previous studies have suggested that environmental perturbations can influence energy metabolism, potentially impacting the biosynthesis of bioactive compounds. However, the specific influence of environmental changes on energy metabolism and subsequent effects on GAs synthesis in G. lucidum remains an understudied area.ResultsWe demonstrated that intracellular ATP deficiency significantly influences GAs accumulation induced by alterations in energy metabolism. Intracellular ATP deficiency was consistently observed under all four known conditions that induce GAs accumulation: heat stress (HS), nitrogen limitation, treatment with 50 µM methyl jasmonate (MeJA), and treatment with 200 µM salicylic acid (SA). Consistent with these findings, silencing the ATP synthase beta subunit (ATPsyn-beta) or treating with oligomycin (Oli), an ATP synthase inhibitor, increased GAs accumulation and induced intracellular ATP deficiency in G. lucidum. Our results revealed an increase in the GAs biosynthetic pathway and increased levels of the GAs precursor acetyl-CoA in mycelia with intracellular ATP deficiency. Enhanced fatty acid β-oxidation was identified as the primary source of additional acetyl-CoA, indicating that this process, induced by intracellular ATP deficiency, is crucial for GAs accumulation.ConclusionsThis study demonstrated that changes in intracellular ATP content respond to environmental perturbations and impact the biosynthesis of GAs, holding substantial implications for production practices. Modulating ATP levels could increase GAs yields, cater to market demands, and reduce costs. The research also furnishes a scientific foundation for optimizing cultivation conditions, employing genetic engineering to refine biosynthetic pathways, and leveraging environmental control to boost production efficiency.

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Dataset Information

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

Background

Results

Conclusions

Publications

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

Similar Datasets

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