解脂耶氏酵母底盘细胞的工程改造及应用
Rewiring and application of
Yarrowia lipolytica chassis cell- 合成生物学 2023年4卷第4期 页码：779-807
- 作者机构：
南京工业大学生物与制药工程学院，材料化学工程国家重点实验室，江苏 南京 211816
- 作者简介：
[ "孙美莉（1990—），女，博士研究生。研究方向为代谢工程与合成生物学。E-mail：meilisun@njtech.edu.cn" ]
[ "纪晓俊（1982—），男，教授，博士生导师。研究方向为代谢工程与合成生物学。E-mail：xiaojunji@njtech.edu.cn" ]
- 基金信息：国家重点研发计划(2021YFC2101100);国家自然科学基金优秀青年科学基金(21922806);江苏省重点研发计划(BE2020782);英国皇家学会牛顿高级学者基金（NAF\R1\20118）
DOI：10.12211/2096-8280.2022-060
中图分类号： Q819收稿：2022-11-02，
修回：2022-12-12，
纸质出版：2023-08-31
- 稿件说明：
移动端阅览
孙美莉， 王凯峰， 陆然， 纪晓俊. 解脂耶氏酵母底盘细胞的工程改造及应用［J］. 合成生物学， 2023， 4（4）： 779-807
SUN Meili， WANG Kaifeng， LU Ran， JI Xiaojun. Rewiring and application of Yarrowia lipolytica chassis cell［J］. Synthetic Biology Journal， 2023， 4（4）： 779-807
孙美莉， 王凯峰， 陆然， 纪晓俊. 解脂耶氏酵母底盘细胞的工程改造及应用［J］. 合成生物学， 2023， 4（4）： 779-807 DOI： 10.12211/2096-8280.2022-060.
SUN Meili， WANG Kaifeng， LU Ran， JI Xiaojun. Rewiring and application of Yarrowia lipolytica chassis cell［J］. Synthetic Biology Journal， 2023， 4（4）： 779-807 DOI： 10.12211/2096-8280.2022-060.
摘要
基于性能卓越的微生物底盘细胞，开发高效的绿色生物制造技术，已经成为合成生物学领域的研究前沿。解脂耶氏酵母作为一种非常规产油酵母，由于其独特的生理生化特征，正迅速成为面向绿色生物制造的合成生物学研究领域的热门底盘细胞之一。近年来，围绕解脂耶氏酵母底盘细胞工程改造的研究与应用日益增多，促进了解脂耶氏酵母底盘细胞的进一步升级。本文总结了针对解脂耶氏酵母底盘细胞的工程改造策略及其在生物制造中的应用，从遗传改造技术及工具开发，基因的表达与调控策略等方面介绍各类合成生物学工具及技术在解脂耶氏酵母中的研究进展，并从底盘细胞合成高附加值产品的研究进展方面介绍了其工程改造效果。最后，对解脂耶氏酵母底盘细胞的应用前景和未来发展方向进行了展望。
Abstract
Engineering microbial chassis cells to efficiently synthesize high value-added products has received increasing attention. This biomanufacturing mode based on excellent performance microbial chassis cells has become the research frontier in the field of synthetic biology.
Yarrowia lipolytica
an unconventional oleaginous yeast
is emerging as one of the popular microbial chassis cells in the field of advanced and green biomanufacturing. This is due to its unique physiological and biochemical characteristics
such as the inherent mevalonate pathway
adequate acetyl-CoA supply
broad substrate spectrum
and high tolerance to multiple extreme environments. These characteristics make
Y. lipolytica
a superior chassis candidate for the advanced and green biomanufacturing. In recent years
the researches and applications on the rewiring of
Y. lipolytica
chassis cell for biomanufacturing have gradually increased
which promoted the further upgrading of
Y. lipolytica
chassis cells. This review firstly describes the development of the genetic elements for rewiring
Y. lipolytica
chassis cell
including promoters
terminators
and selecting markers. Then
this review summarizes the expression modes and integration methods for endogenous and heterogenous genes
including gene expression based on episomal plasmid
genomic integration based on homologous recombination (HR) and non-homologous end joining (NHEJ). This review further summarizes the research progress of various synthetic biol
ogy tools developed for
Y. lipolytica
including various gene overexpression methods
biosensor-based dynamic regulation strategies
CRISPR/Cas-based gene expression regulation methods
and the emerging strategies such as genome-scale metabolic modelling
genome-wide mutational screening
etc
. This review also introduces the achievements of rewiring
Y. lipolytica
chassis cell for the synthesis of different high value-added products
including proteins
organic acids
terpenes
functional sugars and sugar alcohols
fatty acids and their derivatives
flavonoids and polyketides
and amino acid derivatives. In addition
the prospects of
Y. lipolytica
chassis cell-based biomanufacturing are discussed in light of the current progresses
challenges
and trends in this field. Finally
guidelines for building next-generation
Y. lipolytica
chassis cell for production of the aforementioned products are also emphasized.
2
关键词
Keywords
references
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