天然活性多肽的发掘策略和生产技术

Functional discovery and production technology for natural bioactive peptides

活性多肽可以参与生命机体的多种生理活动,对促进人体健康发挥着重要的作用,如降血压、降血糖、降血脂和抗癌等,其创制技术也逐渐成为重要的研究和应用转化方向。本综述旨在总结天然活性多肽的发掘策略和生产技术的研究进展。目前,天然活性多肽的发掘与生产技术主要包括自上而下和自下而上两种方法,其中自上而下方法在多肽发掘方面主要为直接提取鉴定法,在生产技术方面主要包括直接提取法、酶解法和微生物发酵法;自下而上方法在多肽发掘方面包括天然活性多肽改造和数据库发掘方法,在生产技术方面主要方法包括化学合成法、酶合成法、基因重组表达法和无细胞合成法。自上而下的天然多肽制备与功能验证方法存在步骤烦琐、耗费时间长、功能不确定性大、实验与生产成本高以及质量控制难度大等问题;而自下而上的活性多肽合成与功能验证方法适合多肽药物的开发,而难以用于功能食品。随着测序和质谱技术的发展,人们更容易从分子水平获取物种蛋白组信息。以此蛋白组信息为根据,将自上而下和自下而上两种方法结合,可以克服单独使用这两种方法存在的问题,从而为快速开发和生产天然活性多肽提供新的策略。

Bioactive peptides play important roles in promoting human health,such as lowering blood pressure,blood sugar and blood lipid,anti-obesity,and anti-cancer.Thus,exploring functional bioactive peptides and developing efficient production technologies are of crucial importance.Herein,we review the development of function discovery and production technology for natural bioactive peptides.Presently,the top-down and bottom-up approaches are mainly used for the function discovery and production of natural active peptides.The top-down approach includes the direct extraction and identification for functional discovery,and the direct extraction,enzymatic hydrolysis and microbial fermentation for production.The bottom-up approach includes the polypeptide modification and database mining for functional discovery,and the chemical synthesis,enzyme synthesis,recombinant expression and cell-free synthesis for production.The top-down approach is usually associated with complicated process,lower efficiency,higher cost,harder quality control,and uncertain functionality,while the bottom-up approach is more suitable for the development of peptide drugs but difficult to be used for functional foods.With the technology development of sequencing and mass spectrometry,it is easier to obtain the proteomic information of various organisms at the molecular level.Based on the proteomic information,the top-down and bottom-up approaches can be combined to overcome the disadvantages of using these two approaches alone,thus providing a new strategy for the rapid development and production of natural active peptides.