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Rewiring and application of
Pichia pastoris chassis cell- Synthetic Biology Journal Vol. 3, Issue 6, Pages: 1150-1173(2022)
- 作者机构：
华东理工大学生物工程学院，生物反应器工程国家重点实验室，上海 200237
- 作者简介：
- 基金信息：
DOI：10.12211/2096-8280.2022-039
CLC： Q81Received：04 July 2022，
Revised：2022-08-03，
Published：31 December 2022
- 稿件说明：
移动端阅览
刘启， 钱芷兰， 宋丽丽， 要超颖， 徐名强， 任燕娜， 蔡孟浩. 巴斯德毕赤酵母底盘细胞的工程化改造及应用［J］. 合成生物学， 2022， 3（6）： 1150-1173
LIU Qi， QIAN Zhilan， SONG Lili， YAO Chaoying， XU Mingqiang， REN Yanna， CAI Menghao. Rewiring and application of Pichia pastoris chassis cell［J］. Synthetic Biology Journal， 2022， 3（6）： 1150-1173
刘启， 钱芷兰， 宋丽丽， 要超颖， 徐名强， 任燕娜， 蔡孟浩. 巴斯德毕赤酵母底盘细胞的工程化改造及应用［J］. 合成生物学， 2022， 3（6）： 1150-1173 DOI： 10.12211/2096-8280.2022-039.
LIU Qi， QIAN Zhilan， SONG Lili， YAO Chaoying， XU Mingqiang， REN Yanna， CAI Menghao. Rewiring and application of Pichia pastoris chassis cell［J］. Synthetic Biology Journal， 2022， 3（6）： 1150-1173 DOI： 10.12211/2096-8280.2022-039.
摘要
优质的微生物底盘宿主是实现绿色、可持续生物制造的重要平台。巴斯德毕赤酵母底盘宿主因其在蛋白表达和发酵生产中的诸多优势受到了广泛的关注和应用。而作为一种工业甲基营养酵母，其可以有效地利用来源广泛的甲醇作为唯一碳源，使其成为碳一化合物潜在的生物转化平台。近年来，随着合成生物技术和生物制药技术的快速发展，围绕毕赤酵母底盘的工程化改造研究逐渐增多，并取得了卓有成效的进展，促进了毕赤酵母底盘的发展和升级。本文简述了毕赤酵母底盘细胞的发展和应用现状，从基因操纵技术、基因表达调控、代谢工程改造等方面介绍了毕赤酵母的工程化改造策略及应用效果，总结了毕赤酵母中合成生物技术、调控元器件、新型表达平台和生物转化体系的建立与开发情况。在此基础上，进一步强调了毕赤酵母中CRISPR介导的基因编辑及调控、转录系统的重构及人工设计，介绍了其在蛋白表达和化合物合成方面的应用，并分析了其在实际应用中的优势和问题。最后，对毕赤酵母在后续研究中的底盘升级方向和应用场景进行了展望。
Abstract
Microbial chassis hosts are important platforms for green and sustainable biomanufacturing.
Pichia pastoris
has served as a preferred chassis for heterologous protein expression and fermentation production
which is attributed to its numerous advantages in expression capacity
post-translational modification
high cell density culture
and extracellular product purification. Moreover
as an industrial methylotrophic yeast
P. pastoris
effectively utilizes cheap and widely sourced methanol as the sole carbon source
making it a potential biotrans
formation platform for C1 compounds. Recently
scientists have endowed this nonconventional yeast as an efficient microbial cell factory for biosynthesis of small molecule products beyond its traditional role of a protein expression workhorse. The growing of synthetic biology and biopharmaceutical technology has promoted the rapid development on the genetic rewiring of
P. pastoris
chassis host. A series of engineering strategies have been developed to break the restrictions and bottlenecks of
P. pastoris
in both academic and industrial applications. This allowed the updated chassis versions adapting to diversified application scenarios. In this review
we briefly introduce the advances and current status of
P. pastoris
. We describe the development and application of this chassis from the genetic manipulation technology
regulation of gene expression
and metabolic engineering. We summarize the establishment and characterization of synthetic biological techniques
regulatory parts and devices
novel expression platform
and bioconversion system in
P. pastoris
. We emphasize the CRISPR-mediated gene editing
transcription regulation
rewiring of natural transcription system
and the design of artificial biosystems. Then the production of glycoprotein and the synthesis of natural products based on alcohols are concisely summarized. Also
the advantages and limitations of this host in practical application are analyzed and discussed. Finally
we propose the research directions for further updating versions of
P. pastoris
and provide a perspective on their future application scenarios.
2
关键词
Keywords
references
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