纪念王义翘教授：解脂耶氏酵母替代植物油脂的技术瓶颈及展望

徐鹏

doi:10.12211/2096-8280.2021-041

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纪念王义翘教授：解脂耶氏酵母替代植物油脂的技术瓶颈及展望

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- 纪念王义翘教授：解脂耶氏酵母替代植物油脂的技术瓶颈及展望
- In memory of Prof. Daniel I.C. Wang: Engineering Yarrowia lipolytica for the production of plant-based lipids: technical constraints and perspectives for a sustainable cellular agriculture economy
- 合成生物学 2021年2卷第4期页码：509-527
- 作者机构：
  
  1.广东以色列理工学院化学工程系，广东　汕头　515063
  2.马里兰大学巴尔的摩分校化学、生化与环境工程系，马里兰州　巴尔的摩 21250，美国
- 作者简介：
  
  [ "徐鹏（1980—），男，工学博士，于2020年获得“生物技术与生物工程王义翘教授奖” （Biotechnology & Bioengineering Daniel I.C. Wang Award）。研究方向主要涉及代谢工程、合成生物学、生化工程、生物分子绿色制造、智能控制和生化反应网络建模等。E-mail：peng.xu@gtiit.edu.cn" ]
- 基金信息：
- DOI：10.12211/2096-8280.2021-041
  中图分类号： Q81
- 收稿：2021-04-03，
  
  修回：2021-05-12，
  
  纸质出版：2021-08-31
- 稿件说明：
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徐鹏. 纪念王义翘教授：解脂耶氏酵母替代植物油脂的技术瓶颈及展望［J］. 合成生物学， 2021， 2（4）： 509-527

XU Peng. In memory of Prof. Daniel I.C. Wang： Engineering Yarrowia lipolytica for the production of plant-based lipids： technical constraints and perspectives for a sustainable cellular agriculture economy［J］. Synthetic Biology Journal， 2021， 2（4）： 509-527
徐鹏. 纪念王义翘教授：解脂耶氏酵母替代植物油脂的技术瓶颈及展望［J］. 合成生物学， 2021， 2（4）： 509-527 DOI： 10.12211/2096-8280.2021-041.

XU Peng. In memory of Prof. Daniel I.C. Wang： Engineering Yarrowia lipolytica for the production of plant-based lipids： technical constraints and perspectives for a sustainable cellular agriculture economy［J］. Synthetic Biology Journal， 2021， 2（4）： 509-527 DOI： 10.12211/2096-8280.2021-041.

摘要

构建细胞农业经济是解决资源短缺、降低温室气体排放、延缓全球变暖和实现可持续性经济发展的重要手段之一。微生物细胞工厂具有易于遗传改造、便于工程放大和高效利用可再生资源的优势，成为了现代生物制造的重要组成部分。王义翘教授是现代生化工程技术的开创者和奠基人，本人及同事（乔康健博士、胡鹏博士、周康博士等人）在Stephanopoulos实验室所从事的构建油脂细胞工厂的工作，受益于王先生在MIT所创建的生物工程技术中心。植物油脂具有2000多亿美元的年均市场需求，本文从植物油脂需求激增所造成的负面环境效应出发，分析了目前植物油脂的市场供应现状。产油酵母细胞工厂具有替代植物源油脂的巨大潜能。本文围绕产油酵母的代谢工程遗传改造策略，总结了如何提高碳源转化率、油脂产量、油脂生产速率和菌体生长适用性；进一步归纳了构建高效解脂耶氏酵母细胞工厂的主要技术瓶颈，其中包括产油菌株的高通量筛选和表型鉴定技术、产油酵母的代谢调控机制和发酵动力学模型等。作者进一步探讨了以蔗糖作为原材料，生产植物源功能性油脂的经济可行性和技术可行性。作者预测解脂耶氏酵母具有极大的潜力，可以解决当前高附加值油脂（比如用于巧克力生产的可可脂，潜在市场为500亿美元）的市场需求。开发产油酵母微生物资源，提供健康的功能性油脂，将会解决一系列能源、健康食品和环境资源等问题，促进我们迈向低碳性和可持续性的经济运转模式。

Abstract

Developing cellular agriculture economy is one of the solutions to mitigate resource limitation

reduce greenhouse gas emission

slow down global warming as well as achieve true sustainability. Microbial cell factory has become a critical component to advance biomanufactur

ing due to the availability of versatile genetic tools

ease scale-up and the high conversion efficiency of low-cost renewable feedstocks. Prof. Daniel I.C. Wang was one of the trailblazers and founders of biochemical engineering

who built and led the Biotechnology Process Engineering Center (BPEC) at MIT. When I and my colleagues worked as postdoc associates and research scientists in Prof. Stephanopoulos

lab

part of our work on engineering oleaginous yeast cell factory was a direct result of the analytical

imaging and cell culture facility at BPEC. Plant-based oil and fats have an overall market value about $200 billion. Recently

the world has seen a craving for plant oil products

which negatively impacted our environment due to massive-scale deforestation and loss of ecological diversity in tropical regions. We thought oleaginous yeast could be a solution to this problem. Centering around the important genetic targets of the oleaginous species

Yarrowia lipolytica

we summarized the essential metabolic engineering strategies for improving the carbon conversion efficiency (yield)

lipid titer

lipid production rate (productivity) and cell growth fitness. We further analyzed technical constraints that limit our ability to build high oil-yielding yeast cell factory

including high throughput strain screening or phenotyping techniques

the incomplete understanding of the lipogenesis and underlying regulatory mechanism

as well as the lack of well-defined biochemical models to guide bioprocess optimization and scale-up. Further we discussed the technical and economic feasibility of converting sugarcane feedstock to high value plant-based lipids with metabolically engineered

Y. lipolytica

. Our analysis indicates that

Y. lipolytica

has a great potential to address the current market gap of high value plant-based fats (

i.e

. cocoa butter equivalent to make chocolate with a potential market of $50 billions). Engineering oleaginous

yeast to provide plant-based healthy fats will help us address energy

foods

environment and resource challenges

which will surely move us one step closer to a society of low-carbon footprint and sustainable economy.

关键词

Keywords

references

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