Oxidative Stress Induction Is a Rational Strategy to Enhance the Productivity of Antrodia cinnamomea Fermentations for the Antioxidant Secondary Metabolite Antrodin C

Antioxidant
metabolites contribute to alleviating oxidative stress
caused by reactive oxygen species (ROS) in microorganisms. We utilized
oxidative stressors such as hydrogen peroxide supplementation to increase
the yield of the bioactive secondary metabolite antioxidant antrodin
C in submerged fermentations of the medicinal mushroom Antrodia cinnamomea. Changes in the superoxide dismutase
and catalase activities of the cells indicate that ROS are critical
to promote antrodin C biosynthesis, while the ROS production inhibitor
diphenyleneiodonium cancels the productivity-enhancing effects of
H2O2. Transcriptomic analysis suggests that
key enzymes in the mitochondrial electron transport chain are repressed
during oxidative stress, leading to ROS accumulation and triggering
the biosynthesis of antioxidants such as antrodin C. Accordingly,
rotenone, an inhibitor of the electron transport chain complex I,
mimics the antrodin C productivity-enhancing effects of H2O2. Delineating the steps connecting oxidative stress
with increased antrodin C biosynthesis will facilitate the fine-tuning
of strategies for rational fermentation process improvement.

抗氧化代谢物可缓解微生物体内由活性氧簇（ROS）介导的氧化应激。本研究通过添加过氧化氢等氧化应激诱导因子，提升药用真菌牛樟芝（Antrodia cinnamomea）深层发酵体系中活性次生代谢产物——抗氧化成分安糖C（antrodin C）的产量。细胞中超氧化物歧化酶与过氧化氢酶的活性变化表明，ROS对促进安糖C的生物合成具有关键作用；而ROS生成抑制剂二苯基碘鎓盐可抵消H₂O₂的产量提升效应。转录组分析结果显示，氧化应激过程中线粒体电子传递链的关键酶类受到抑制，进而导致ROS积累并触发安糖C等抗氧化成分的生物合成。据此，电子传递链复合物I抑制剂鱼藤酮可模拟H₂O₂提升安糖C产量的效应。阐明氧化应激与安糖C生物合成增强之间的调控通路，将有助于精准优化理性发酵工艺的改进策略。