非常规酵母底盘细胞的设计构建与功能重塑

刘夏; 黄璐; 王钦宏; 段守富

doi:10.12211/2096-8280.2026-095

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非常规酵母底盘细胞的设计构建与功能重塑

特约评述 | 更新时间：2026-10-28

- 非常规酵母底盘细胞的设计构建与功能重塑
- Engineering and Functional Reprogramming of Non-Conventional Yeast Chassis Cells
- 合成生物学 2026年页码：1-23
- 作者机构：
  
  1.微生物多样性与资源创新利用全国重点实验室，中国科学院微生物研究所，北京 100101
  2.中国科学院大学，北京100049
  3.低碳合成工程生物学全国重点实验室，中国科学院天津工业生物技术研究所，天津 300300
- 作者简介：
  
  刘夏（1997-），女，博士研究生，研究方向：非常规酵母的遗传操作体系构建。
  段守富（1989-），男，研究员，博士生导师，研究方向：1.酵母菌多样性利用与抗逆功能元件挖掘；2.酵母菌基因组与表观基因组协同进化机制；3.非粮新型酵母底盘构建。
- 基金信息：
  
  中国科学院三年行动方案项目(E4SJ1809)
- DOI：10.12211/2096-8280.2026-095
  中图分类号： Q933
- 收稿：2026-09-01，
  
  修回：2026-10-24，
  
  网络首发：2026-10-28，
- 稿件说明：
移动端阅览
刘夏，黄璐，王钦宏，段守富. 非常规酵母底盘细胞的设计构建与功能重塑［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-095

LIU Xia， HUANG Lu， WANG Qinhong， DUAN Shoufu. Engineering and Functional Reprogramming of Non-Conventional Yeast Chassis Cells［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-095
刘夏，黄璐，王钦宏，段守富. 非常规酵母底盘细胞的设计构建与功能重塑［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-095 DOI：

LIU Xia， HUANG Lu， WANG Qinhong， DUAN Shoufu. Engineering and Functional Reprogramming of Non-Conventional Yeast Chassis Cells［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-095 DOI：

摘要

非常规酵母底物利用范围广、环境耐受能力强，可弥补常规酿酒酵母在工业生物制造中的不足，是极具潜力的真核生物底盘细胞。本文首先综述非常规酵母的天然优势与多元化工业应用，进而系统梳理构建非常规酵母底盘细胞的三大核心技术：遗传调控元件的开发与表征、CRISPR基因编辑工具的设计与优化、基于代谢通路重构的细胞工厂设计，完整覆盖从分子元件挖掘、遗传操作工具开发到代谢网络重编程的技术链条。针对当前非常规酵母研究中宿主特异性强、通用工具匮乏、代谢认知模糊及产业转化迟滞等关键瓶颈，本文提出“实验室适应性进化-多组学深度解析-人工智能驱动设计”深度融合的研究思路，旨在加速其智能化创制与工程化改造。最后，本文展望未来四大重点方向：新型种质资源的系统挖掘、通用型分子工具箱的开发、数据驱动的智能设计体系构建，以及从实验室到产业化的转化路径探索，强调通过多学科交叉融合，推动非常规酵母底盘细胞从基础研究迈向规模化生物制造应用。

Abstract

Non-conventional yeasts are promising eukaryotic chassis for sustainable biomanufacturing because they combine the genetic accessibility of yeast with broad substrate utilization

strong stress tolerance

efficient protein secretion and species-specific metabolic capabilities. Compared with

Saccharomyces cerevisiae

they can use methanol

organic acids

pentoses

glycerol and other low-cost or non-food feedstocks

while supporting production of microbial oils

recombinant proteins

organic acids

biosurfactants

single-cell protein and other value-added products. This review summarizes the natural chassis advantages and industrial applications of non-conventional yeasts and considers current progress through three interconnected engineering pillars: discovery and characterization of genetic regulatory elements

development of host-adapted CRISPR genome-editing systems

and reconstruction of metabolic pathways and cell factories. Promoters

terminators

untranslated regulatory regions

autonomous replication sequences and centromeres provide the basis for tunable expression and stable vector maintenance

whereas species-specific control of guide-RNA expression

Cas protein activity and DNA repair must be considered when designing precise

multiplex genome-editing platforms. Metabolic engineering is expanding from individual pathway installation to coordinated regulation of precursor supply

cofactor and energy balance

organelle compartmentalization

product transport and cellular stress. Linking host physiology with carbon-flow redistribution

redox control and product toxicity is particularly important because these interactions determine whether laboratory improvements can withstand industrial fermentation. Integrated genom

ics

transcriptomics

proteomics

metabolomics

epigenomics and single-cell measurements can connect genotype

regulation

metabolic flux and phenotype

while genome-scale metabolic models can guide the selection of essential genes

competing branches and rate-limiting nodes. Adaptive laboratory evolution complements rational design by enriching phenotypes that are difficult to specify in advance; combined with resequencing and multi-omics analysis

it can reveal the genetic basis of stress tolerance and metabolic adaptation. Artificial intelligence may support regulatory-element design

protein engineering

target prioritization and automated design-build-test-learn cycles

although its performance remains limited by uneven datasets and strong host specificity. The field must therefore address shortages of portable genetic toolkits

incomplete metabolic knowledge

limited industrial robustness and scale-up barriers. These constraints are especially important across phylogenetically diverse hosts and industrial process conditions. Future progress will depend on systematic exploration of yeast biodiversity

standardized molecular toolboxes

validated computational workflows and closer integration of strain engineering with fermentation and downstream processing. Together

these advances show how interdisciplinary integration can move non-conventional yeast beyond host-specific trial and error toward predictive

modular chassis engineering

accelerating its transition from fundamental research to large-scale biomanufacturing.

关键词

Keywords

references

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