摘要
虾青素是一种高附加值的抗氧化萜类物质,具有很强的抗氧化活性,同时还具有抗癌、预防炎症、护眼等诸多功效.随着合成生物学技术的不断发展,利用微生物发酵法合成虾青素是实现虾青素工业化生产最有效的途径之一,也更能满足消费者对天然化合物的需求.目前,生产虾青素的微生物包括细菌、真菌、藻类等.本文系统介绍了虾青素的结构性质和生产方法,重点讲述了虾青素天然合成以及外源构建的合成路径,总结了不同微生物如雨生红球藻、酵母和大肠杆菌生产虾青素的最新进展,分析了利用基因工程和发酵过程调控手段提高虾青素产量的方法.未来,通过代谢工程等手段(如虾青素合成基因过表达、使用高强度启动子、代谢途径优化等)可提高虾青素产量,以进一步增加虾青素在食品、医疗、化妆品和饲料等产业的应用.
Abstract
Astaxanthin is a value-added terpene with strong antioxidant activity as well as other physiological functions,such as anti-cancer,enhancing immunity,eye protection,and cardio-cerebrovascular protection.Natural astaxanthin mainly comes from algae and aquatic crustaceans such as lobster shell.Astaxanthin presents with stereoisomerism and geometric isomerism,which have different biological activities and applications.Currently,astaxanthin in the market is obtained primarily through natural extraction from Haematococcus pluvialis or Xanthophyllomyces dendrorhous and chemical synthesis as well.While H.pluvialis has a long growth cycle and high light demand,leading to low biomass productivity and extraction rate for high production cost of astaxanthin,X.dendrorhous has a low astaxanthin yield and is easy to degenerate,making them challenging for the large-scale commercial production.The chemical synthesis of astaxanthin involves multiple reactions with complicated processes,producing mixed isomers and various byproducts,which consequently compromises its antioxidant capacity.Moreover,the assimilation and utilization of chemically synthesized astaxanthin in vivo is poor compared to its natural product,making it not suitable for being used by human being.With the continuous development of synthetic biology,microbial fermentation has been developed as an effective way for the commercial production of astaxanthin to better meet consumer demand.At present,astaxanthin-producing microorganisms include bacteria,fungi,and algae.This review introduces astaxanthin's structure,properties,production methods,and processes for its extraction and purification,with an emphasis on natural and engineered biosynthetic pathways.The latest progress in the production of astaxanthin by different microorganisms such as H.pluvialis,Yarrowia lipolytica and Escherichia coli is summarized,along with strategies for increasing astaxanthin production through genetic engineering and fermentation process optimization.Future metabolic engineering strategies are proposed,such as over-expression of astaxanthin synthesis genes,promoters with higher substitution intensity,subcellular localization,metabolic pathway optimization,etc,to increase astaxanthin yield for wide usage in food,medical,cosmetic and feed industries.
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