Production of an antihypertensive peptide from milk by the brown rot fungus Neolentinus lepideus
Production of an antihypertensive peptide from milk by the brown rot fungus Neolentinus lepideus
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DOI：
10.1007/s00217-020-03530-y
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发表时间：
2020-06-08
影响因子：
3.3
通讯作者：
Nabika, Toru
中科院分区：
文献类型：
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作者：
Okamoto, Kenji;Kawamura, Sayo;Nabika, Toru
发酵乳已被证明通过其生物活性肽对人类健康具有有益的影响。乳糖发酵褐腐真菌Neolentinus lepideus已被证明发酵牛奶;然而，其产生生物活性肽的能力尚未被探索。因此，本研究的目的是调查能力N。lepideus用于在发酵乳中生产抗高血压肽并表征肽。以9%脱脂乳为底物，用N.麻风病与市售的含有Ile-Pro-Pro和Val-Pro-Pro的酸奶相比，发酵乳表现出更高的血管紧张素I转化酶（ACE）抑制活性。作为通过反相高效液相色谱分离和纯化的结果，随后通过肽测序和MS分析，二肽Tyr-Pro（YP）被鉴定为活性肽。发酵乳中YP的浓度高达450 μ g/ml，比ACE抑制的IC 50高两倍以上。随后，通过静脉注射该肽验证了YP的抗高血压作用，其在遗传性高血压大鼠模型中表现出显著的血压降低。此外，转录组学分析揭示了羧肽酶对提高YP产量的可能作用。这些结果表明，利用担子菌发酵生产生物活性肽是一种可行的方法，因此，可以应用于开发一种经济有效的功能肽大规模生产系统。
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 mu g/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.