Fermented milk has been shown to have beneficial effects on human health exerted through its bioactive peptides. The lactose-fermenting brown rot fungus Neolentinus lepideus has been shown to ferment milk; however, its ability to produce bioactive peptides has not been explored. This study, therefore, aimed to investigate the ability N. lepideus for the production of antihypertensive peptides in fermented milk and to characterize the peptides. Here we have used 9% skim milk as the substrate and fermented it with the mycelia of N. lepideus. The fermented milk exhibited higher angiotensin I-converting enzyme (ACE) inhibitory activity as compared to the commercially available sour milk containing Ile-Pro-Pro and Val-Pro-Pro. As a result of isolation and purification by reverse-phase high-performance liquid chromatography, followed by peptide sequencing and MS analysis, the dipeptide Tyr-Pro (YP) was identified as an active peptide. The concentration of YP in the fermented milk reached up to 450 μg/ml, which was > twofold higher than the IC₅₀ for ACE inhibition. Subsequently, the antihypertensive effect of YP was validated through intravenous injection of the peptide, which exhibited a significant lowering of blood pressure in a rat model of genetic hypertension. In addition, the transcriptomic analysis revealed the probable role of the carboxypeptidases for the increased yield of YP. These results together indicated that the fermentation with basidiomycete fungus could be a viable approach to produce bioactive peptides, and may, therefore, be applicable in the development of a cost-effective mass production system for functional peptides.

中文翻译：

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褐腐真菌Neurotinus lepideus从牛奶中生产降压肽

发酵乳通过其生物活性肽已显示出对人类健康的有益作用。乳糖发酵的褐腐真菌Neolentinus lepideus已被证明可以发酵牛奶。然而，尚未探索其产生生物活性肽的能力。因此，本研究旨在研究轻皮猪笼草在发酵乳中生产降压肽的能力并鉴定其特征。在这里，我们使用了9％的脱脂牛奶作为底物，并用N. lepideus的菌丝体对其进行了发酵。。与市售的含Ile-Pro-Pro和Val-Pro-Pro的酸乳相比，发酵乳表现出更高的血管紧张素I转换酶（ACE）抑制活性。通过反相高效液相色谱进行分离和纯化，然后进行肽测序和MS分析，结果表明，二肽Tyr-Pro（YP）被鉴定为活性肽。发酵乳中YP的浓度高达450μg/ ml，比IC ₅₀高两倍抑制ACE。随后，通过静脉内注射该肽验证了YP的降压作用，在遗传性高血压大鼠模型中血压显着降低。此外，转录组分析揭示了羧肽酶可能对提高YP产量具有重要作用。这些结果共同表明，用担子菌属真菌发酵可能是生产生物活性肽的可行方法，因此可能适用于开发功能性肽的经济有效的大规模生产系统。