合成生物技术驱动天然的真核油脂细胞工厂开发

Synthetic biotechnology drives the development of natural eukaryotic lipid cell factories

油脂是重要的工业原料,也是人类生存的三大营养素之一。为避免因国际环境变化导致外部资源进口遭到封锁,我国亟需建设、补充和完善油脂供给的新方式。以丰富、廉价的生物质原料替代化石原料生产食用油脂和功能性油脂,在保障国家能源安全、粮食安全方面意义重大。细菌、酵母、霉菌、微藻等多种微生物具有利用葡萄糖、木质纤维素、淀粉、甘油甚至一碳化合物等原料合成脂肪酸的能力。由于微生物,特别是产油真菌相比产油植物和动物具有生产周期短、易于大规模生产、占地少、受天气影响小、原料来源丰富等优势,近年来备受学术界和产业界重视。然而,如何获取生产效率高且鲁棒性强的微生物油脂细胞工厂,仍然面临着使能工具有限、油脂产量不高、油脂组分难以控制等诸多挑战。近年来,合成生物学技术的发展为本领域的研究提供了新的资源、工具和思路。使得产油微生物研究在遗传操作工具创制、代谢途径改造以及高附加值产品开发等方面不断获得突破。本文聚焦于真核油脂细胞工厂的开发,从天然产油底盘菌株的基因元件、遗传转化方法、基因编辑工具的开发,油脂细胞工厂代谢途径的重构/调试以及向高附加值脂质化学品方向的升级等方面,系统总结了合成生物技术驱动油脂细胞工厂开发的研究进展,可为后续研究提供借鉴。

Lipids are important industrial raw materials and one of the three major nutrients for human survival.In order to avoid the blockade of external resource imports due to unpredictable international market,we urgently need to build new methods for lipids supply.Biomass is the only kind of physical resource based on carbon among many renewable resources.Therefore,The production of edible and functional lipids with abundant and cheap biomass materials instead of fossil materials is of great significance in ensuring national energy security and food security.Bacteria,yeast,mold,microalgae and some other microorganisms have the potential in using glucose,lignocellulose,starch,glycerol or even one carbon compounds to synthesize fatty acids.Due to the advantages of short production cycle,easy large-scale production,less land occupation,less impact of climate change and abundant raw material sources comparing with lipips from plants and animals,microbial lipid production has attracted much attention from academia and industry in recent years.However,there are still many challenges on how to obtain efficient and robust microbial lipid cell factories,such as limited enabling tools,low lipid production and difficult control of lipid components.The development of synthetic biology then provides new resources,tools and ideas for research in this field in recent years.Thus the research of lipid producing microorganisms has made continuous breakthroughs in the creation of genetic manipulation tools,the engineering of lipip biosynthesis pathways and the development of high value-added products.This review focuses on the genetic elements of natural lipid-producing chassis strains,genetic transformation methods,genome editing tools development,the reconstruction/debugging of the metabolic pathways of lipid cell factories,and the upgrade to high value-added lipid chemicals.By systematically summarized the research progress of synthetic biotechnology in driving the development of lipid cell factories,we very much hope to provide reference for future research in this area.