Increased production of ganoderic acids by overexpression of homologous farnesyl diphosphate synthase and kinetic modeling of ganoderic acid production in Ganoderma lucidum
Increased production of ganoderic acids by overexpression of homologous farnesyl diphosphate synthase and kinetic modeling of ganoderic acid production in Ganoderma lucidum
复制标题
通过同源法尼基二磷酸合酶的过表达增加灵芝酸的产量以及灵芝中灵芝酸生产的动力学模型
DOI：
10.1186/s12934-019-1164-3
复制
发表时间：
2019-06-28
影响因子：
6.4
通讯作者：
Xu, Jun-Wei
中科院分区：
文献类型：
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作者：
Fei, Yu;Li, Na;Xu, Jun-Wei
灵芝酸（GanodericAcids，GAs）是从药用真菌灵芝（Ganodericlucidum）中提取的一种具有抗癌等重要药理活性的化合物。为了提高GAs的产量，将同源的法呢基二磷酸合酶（FPS）基因在G. lucidum。此外，通过建立相应的数学模型，研究了FPS基因过表达对GA产量的影响。GA-T、GA-S和GA-Me的含量分别为2.76 mg/100 mg干重（DW）、41 ± 2、21 ± 5和28 ± 1 μg/100 mg DW，分别比对照组提高2.28、2.27、2.62和2.80倍。在GA生物合成过程中，角鲨烯合酶（SQS）和羊毛甾醇合酶（LS）基因的转录水平分别上调了2.28倍和1.73倍。lucidum。此外，所建立的非结构化模型对G. lucidum。动力学过程分析表明，FPS基因过表达对GA产量的影响比对细胞生长的影响更大。FPS基因过表达可使非生长相关常数β（1.151）高于生长相关常数α（0.026）。lucidum。所建立的数学模型对于在未来的大型生物反应器中开发更好的GA生产过程是有用的。
BackgroundGanoderic acids (GAs), derived from the medicinal mushroomGanoderma lucidum, possess anticancer and other important pharmacological activities. To improve production of GAs, a homologous farnesyl diphosphate synthase (FPS) gene was overexpressed inG. 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 2.76 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 transgenicG. lucidum. In addition, the developed unstructured models had a satisfactory fit for the process of GA production in submerged cultures ofG. 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-constantβ(1.151) over the growth-associated-constantα(0.026) in the developed models.ConclusionsFPS gene overexpression is an effective strategy to improve the production of GAs inG. lucidum. The developed mathematical models are useful for developing a better GA production process in future large-scale bioreactors.