母乳结构脂的生物合成研究进展：从酶法催化到微生物细胞工厂合成

刘芮存; 陈晓艳; 赵健; 蔡佩言; 吴若男; 毛跃建; 尹升明

doi:10.12211/2096-8280.2026-010

您当前的位置：

首页 >

文章列表页 >

母乳结构脂的生物合成研究进展：从酶法催化到微生物细胞工厂合成

特约评述 | 更新时间：2026-05-26

- 母乳结构脂的生物合成研究进展：从酶法催化到微生物细胞工厂合成
- Advances in the Biosynthesis of Human Milk Fat Substitutes： From Enzymatic Catalysis to Microbial Cell Factories
- 合成生物学 2026年页码：1-18
- 作者机构：
  
  内蒙古蒙牛乳业（集团）股份有限公司全球研发创新中心，呼和浩特 011500，内蒙古
- 作者简介：
  
  刘芮存（1990—），女，博士，副研究员。研究方向为合成生物学驱动的食品生物制造研究，融合蛋白质设计与人工智能等交叉学科，推动技术成果的产业转化。
  毛跃建（1981—），男，博士，高级工程师。研究方向为利用微生物组学及分子生物学的方法研究益生菌的健康功效及作用机制，解析菌株功能并推动其在乳品及健康食品领域的产业化应用。
  尹升明（1987—），男，博士。研究方向为生物合成功能性新原料的创新研发与市场转化。
- 基金信息：
  
  内蒙古自治区自然科学基金项目青年基金项目(2025QN03074)
- DOI：10.12211/2096-8280.2026-010
  中图分类号： Q81
- 收稿：2026-03-03，
  
  修回：2026-05-22，
  
  网络首发：2026-05-26，
- 稿件说明：
移动端阅览
刘芮存，陈晓艳，赵健，蔡佩言，吴若男，毛跃建，尹升明. 母乳结构脂的生物合成研究进展：从酶法催化到微生物细胞工厂合成［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-010

LIU Ruicun， CHEN Xiaoyan， ZHAO Jian， CAI Peiyan， WU Ruonan， MAO Yuejian， YIN Shengming. Advances in the Biosynthesis of Human Milk Fat Substitutes： From Enzymatic Catalysis to Microbial Cell Factories［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-010
刘芮存，陈晓艳，赵健，蔡佩言，吴若男，毛跃建，尹升明. 母乳结构脂的生物合成研究进展：从酶法催化到微生物细胞工厂合成［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-010 DOI：

LIU Ruicun， CHEN Xiaoyan， ZHAO Jian， CAI Peiyan， WU Ruonan， MAO Yuejian， YIN Shengming. Advances in the Biosynthesis of Human Milk Fat Substitutes： From Enzymatic Catalysis to Microbial Cell Factories［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-010 DOI：

摘要

母乳中的脂肪是婴幼儿营养的核心，其营养功能不仅取决于脂肪酸组成，更依赖脂肪酸在甘油骨架上的立体特异性分布。实现其立体结构的精准重构，是实现母乳脂肪功能模拟的关键科学前提。酶法催化凭借脂肪酶优异的位置选择性，是目前合成母乳结构脂（human milk fat substitutes，HMFS）的主流技术，但在结构精准性、原料依赖和规模化成本等方面仍面临挑战。合成生物学的发展为HMFS的创制提供了新的路径，通过构建高效微生物细胞工厂，实现以廉价碳源为原料的结构脂肪可编程合成。本文系统性比较了不同技术路线在结构精准性、工艺复杂度与产业化潜力方面的优势与局限，探讨了人工智能等新兴工具的应用潜力，并对未来HMFS生物制造的发展方向做出分析与展望。借助合成生物学及人工智能技术，设计并构建高效细胞工厂，有望将HMFS的生产推入精准、高效、可持续的生物制造新阶段，为婴幼儿营养健康提供更优质的解决方案。

Abstract

Human milk fat (HMF) serves as a primary energy source and a vital nutritional component for infant development. Its physiological functions are determined not only by its diverse fatty acid composition but

more critically

by the stereospecific positional distribution patterns of these fatty acids on the glycerol backbone. Specifically

fatty acid profiles with sn-2 preference are a key feature of triacylglycerols (TAG). In particular

the predominance of palmitic acid at the sn-2 position is a hallmark of HMF

facilitating optimal calcium absorption and intestinal health in neonates. Therefore

the precise reconstruction of these stereospecific structures represents a fundamental scientific prerequisite for achieving functional mimicry of human milk in infant formulas. Historically

enzymatic catalysis

leveraging the excellent positional selectivity of lipases

was the pioneering technology for synthesizing human milk fat substitutes (HMFS). It remains the current mainstream approach; however

it still faces challenges in structural precision

feedstock dependence

and scaling costs. The emergence of synthetic biology offers a transformative paradigm shift for the de novo synthesis of HMFS. By constructing efficient microbial cell factories

researchers can achieve programmable synthesis of structured lipids from inexpensive carbon sources

such as glucose or lignocellulosic biomass. This review systematically compares the advantages and limitations of different technical routes regarding structural fidelity

engineering complexity

and industrial potential. Within the framework

we highlight systematic engineering strategies for microbial lipid synthesis

ranging from the selection and adaptation of optimal chassis cells to the elucidation of endogenous metabolic pathways and the rational redesign of key enzymes

to achieve desired outcomes. We also explore the potential applications of emerging tools

such as artificial intelligence

and provide an outlook on the future development of HMFS biomanufacturing. By leveraging synthetic biology and AI-assisted design to construct efficient cell factories

it is expected that HMFS production will enter a new era of precise

efficient

and sustainable biomanufacturing

offering improved nutritional solutions for infant health.

关键词

Keywords

references

WEI W , JIN Q , WANG X . Human milk fat substitutes: Past achievements and current trends [J ] . Prog Lipid Res , 2019 , 74 : 69 - 86 .

CHEN Y J , ZHOU X H , HAN B , et al . Composition analysis of fatty acids and stereo-distribution of triglycerides in human milk from three regions of China [J ] . Food Res Int , 2020 , 133 : 109196 .

LIU Q , ZHAO J , LIU Y , et al . Advances in analysis, metabolism and mimicking of human milk lipids [J ] . Food Chem , 2022 , 393 : 133332 .

INNIS S M . Human milk: maternal dietary lipids and infant development [J ] . Proceedings of the Nutrition Society , 2007 , 66 : 397 - 404 .

DELPLANQUE B , GIBSON R , KOLETZKO B , et al . Lipid Quality in Infant Nutrition: Current Knowledge and Future Opportunities [J ] . J Pediatr Gastroenterol Nutr , 2015 , 61 ( 1 ): 8 - 17 .

JIANG X , ZOU X , CHAO Z , et al . Preparation of Human Milk Fat Substitutes: A Review [J ] . Life (Basel) , 2022 , 12 ( 2 ).

HONG C R , JEON B J , PARK K-M , et al . An Overview of Structured Lipid in Food Science: Synthesis Methods, Applications, and Future Prospects [J ] . Journal of Chemistry , 2023 , 2023 ( 1 ): 1222373 .

KOWALSKI B , TARNOWSKA K , GRUCZYŃSKA E . The properties of the mixture of beef tallow and rapeseed oil with a high content of tallow after chemical and enzymatic interesterification [J ] . Grasas Y Aceites , 2005 , 56 : 267 - 75 .

WANG Z , LIU L , LIU L , et al . 1,3-Dioleoyl-2-palmitoylglycerol-rich triacylglycerol characterization by three processing methods [J ] . International Journal of Food Properties , 2019 , 22 ( 1 ): 1156 - 71 .

KIM B H , AKOH C C . Recent Research Trends on the Enzymatic Synthesis of Structured Lipids [J ] . J Food Sci , 2015 , 80 ( 8 ): C1713 - 24 .

ZHOU J , LEE Y Y , MAO Y , et al . Future of Structured Lipids: Enzymatic Synthesis and Their New Applications in Food Systems [J ] . Foods , 2022 , 11 ( 16 ).

LIU Z , DAI L , LIU D , et al . Progress and perspectives of enzymatic preparation of human milk fat substitutes [J ] . Biotechnol Biofuels Bioprod , 2022 , 15 ( 1 ): 118 .

TACIAS-PASCACIO V G , ABELLANAS-PEREZ P , DE ANDRADES D , et al . A comprehensive review of lipase-catalyzed acidolysis as a method for producing structured glycerides [J ] . Int J Biol Macromol , 2025 , 309 ( Pt 3 ): 142878 .

SHI S , WANG Z , SHEN L , et al . Synthetic biology: a new frontier in food production [J ] . Trends Biotechnol , 2022 , 40 ( 7 ): 781 - 803 .

刘龙 , 路福平 , 陈坚 , et al . 合成生物学与未来食品 [J ] . 生物技术通报 , 2025 , 41 ( 11 ): 1 - 3 .

LIU L , LU F P , CHEN J , et al . Synthetic Biology and Future Food [J ] . China Biotechnology , 2025 , 41 ( 11 ): 1 - 3 .

丁明珠 , 李炳志 , 王颖 , et al . 合成生物学重要研究方向进展 [J ] . 合成生物学 , 2020 , 1 ( 01 ): 7 - 28 .

ZHANG X B , ZHU C S , CHEN R Y , et al . Policy planning and industrial development of agricultural synthetic biology [J ] . Synthetic Biology Journal , 2025 , 6 ( 5 ): 1224 - 1242 .

苏娟娟 , 郑家文 , 苗润泽 , et al . 微生物油脂与植物油脂的合成生物制造 [J ] . 合成生物学 , 2025 , 6 ( 05 ): 1167 - 83 .

SU J J , ZHENG J W , MIAO R Z , et al . Biosynthesis and manufacture of microbial oils and vegetable oils [J ] . Synthetic Biology Journal , 2025 , 6 ( 05 ): 1167 - 1183 .

ZHAO J , LIU Q , LIU Y , et al . Quantitative profiling of glycerides, glycerophosphatides and sphingolipids in Chinese human milk with ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry [J ] . Food Chem , 2021 , 346 : 128857 .

WANG Y H , MAI Q Y , QIN X L , et al . Establishment of an evaluation model for human milk fat substitutes [J ] . J Agric Food Chem , 2010 , 58 ( 1 ): 642 - 9 .

ZOU X Q , HUANG J H , JIN Q Z , et al . Model for human milk fat substitute evaluation based on triacylglycerol composition profile [J ] . J Agric Food Chem , 2013 , 61 ( 1 ): 167 - 75 .

YU J , YAN Z , MI L , et al . Medium- and long-chain triacylglycerols and di-unsaturated fatty acyl-palmitoyl-glycerols in Chinese human milk: Association with region during the lactation [J ] . Front Nutr , 2022 , 9 : 1040321 .

CHEN X , YANG M , WEI W , et al . A Novel Infant Formula with Medium- and Long-Chain Triacylglycerols and sn-2 Palmitate Supports Adequate Growth and Lipid Absorption in Healthy Term Infants [J ] . Nutrients , 2025 , 17 ( 9 ).

INNIS S . Palmitic Acid in Early Human Development [J ] . Critical reviews in food science and nutrition , 2015 , 56 .

TU A , MA Q , BAI H , et al . A comparative study of triacylglycerol composition in Chinese human milk within different lactation stages and imported infant formula by SFC coupled with Q-TOF-MS [J ] . Food Chem , 2017 , 221 : 555 - 67 .

YU J , WEI W , WANG F , et al . Evaluation of total, sn-2 fatty acid, and triacylglycerol composition in commercial infant formulas on the Chinese market: A comparative study of preterm and term formulas [J ] . Food Chem , 2022 , 384 : 132477 .

戴逸 , 戴智勇 , 张岩春 , et al . 市售婴幼儿配方乳粉中脂肪酸组成分析 [J ] . 中国油脂 , 2019 , 44 ( 03 ): 154 - 7 .

DAI Y , DAI Z Y , ZHANG Y C , et al . Fatty acid composition in infant formula milk powder on sale [J ] . China Oils and Fats , 2019 , 44 ( 03 ): 154 - 157 .

ZOU X , HUANG J , JIN Q , et al . Lipid composition analysis of milk fats from different mammalian species: potential for use as human milk fat substitutes [J ] . J Agric Food Chem , 2013 , 61 ( 29 ): 7070 - 80 .

ALVES V , DE FIGUEIREDO F G , LUCCAS V , et al . Structuration of lipid bases zero-trans and palm oil-free for food applications [J ] . Food Res Int , 2024 , 192 : 114683 .

ZHANG L S , CHU M Y , ZONG M-H , et al . Efficient Production of 1,3‐Dioleoyl‐2‐Palmitoylglycerol through Rhodococcus opacus Fermentation [J ] . Journal of the American Oil Chemists' Society , 2020 , 97 .

ZHANG L S , CHU M Y , ZONG M H , et al . Facile and Green Production of Human Milk Fat Substitute through Rhodococcus opacus Fermentation [J ] . J Agric Food Chem , 2020 , 68 ( 35 ): 9368 - 76 .

HAN Y , YUE K , BI Y , et al . Interesterified Fat Facilitated the Synthesis of UPU Structured Lipid Enriched With α-Linolenic Acid Through Rhodococcus opacus Fermentation [J ] . Journal of the American Oil Chemists' Society , 2025 , 102 ( 12 ): 1693 - 700 .

BHUTADA G , MENARD G , BHUNIA R K , et al . Production of human milk fat substitute by engineered strains of Yarrowia lipolytica [J ] . Metab Eng Commun , 2022 , 14 : e00192 .

ZHANG C , ZHOU X , WEI W , et al . De novo production of 1,3-olein-2-palmitin (OPO) and 1-olein-2-palmitin-3-linolein (OPL) by multiplexed reconstruction of lipid metabolism in yeasts [J ] . Metab Eng , 2026 , 94 : 1 - 14 .

LI Y , ZHANG C , HUANG H , et al . Engineering the substrate tunnel of diacylglycerol acyltransferase ScDGA1 enhances triacylglycerol biosynthesis in Saccharomyces cerevisiae [J ] . Int J Biol Macromol , 2026 , 347 : 150813 .

CHEN J , LEE W J , QIU C , et al . Immobilized Lipase in the Synthesis of High Purity Medium Chain Diacylglycerols Using a Bubble Column Reactor: Characterization and Application [J ] . Front Bioeng Biotechnol , 2020 , 8 : 466 .

LEE Y Y , TANG T K , CHAN E S , et al . Medium chain triglyceride and medium-and long chain triglyceride: metabolism, production, health impacts and its applications - a review [J ] . Crit Rev Food Sci Nutr , 2022 , 62 ( 15 ): 4169 - 85 .

ZHANG Z , ZHANG S , LEE W J , et al . Production of Structured Triacylglycerol via Enzymatic Interesterification of Medium-Chain Triacylglycerol and Soybean Oil Using a Pilot-Scale Solvent-Free Packed Bed Reactor [J ] . Journal of the American Oil Chemists' Society , 2020 , 97 ( 3 ): 271 - 80 .

NI X , FENG T , ZHANG Y , et al . Application Progress of Immobilized Enzymes in the Catalytic Synthesis of 1,3-Dioleoyl-2-palmitoyltriglyceride Structured Lipids [J ] . Foods , 2025 , 14 ( 3 ).

WANG X , JIANG C , XU W , et al . Enzymatic synthesis of structured triacylglycerols rich in 1,3-dioleoyl-2-palmitoylglycerol and 1-oleoyl-2-palmitoyl-3-linoleoylglycerol in a solvent-free system [J ] . LWT , 2020 , 118 : 108798 .

GU S , FENG F , LI Y , et al . Aspergillus oryzae Lipase-Catalyzed Synthesis of Dioleoyl; Palmitoyl-Rich Triacylglycerols in Two Reactors [J ] . Journal of the American Oil Chemists' Society , 2016 , 93 ( 10 ): 1347 - 54 .

QIN X L , WANG Y M , WANG Y H , et al . Preparation and characterization of 1,3-dioleoyl-2-palmitoylglycerol [J ] . J Agric Food Chem , 2011 , 59 ( 10 ): 5714 - 9 .

SUN D , LI S , SHANG J , et al . Process optimization of simultaneous enzymatic production of 1,3-dioleoyl-2-palmitoylglycerol and 1-oleoyl-2-palmitoyl-3-linoleoylglycerol [J ] . Journal of the American Oil Chemists' Society , 2021 , 98 ( 12 ): 1167 - 76 .

LI Y , ZHANG Y , ZHOU Y , et al . A novel and controllable method for simultaneous preparation of human milk fat substitutes (OPL, OPO and LPL): two-step enzymatic ethanolysis-esterification strategy [J ] . Food Res Int , 2023 , 163 : 112168 .

ZHU Q , ZHU C , LI S , et al . A novel method for preparation of human milk fat substitute enriched with 1-oleoyl-2-palmitoyl-3-linoleoylglycerol: stepwise enzymatic acidolysis strategy [J ] . LWT , 2025 , 234 : 118581 .

VERMELHO A B , CARDOSO V D S , DOMINGOS L T S , et al . Advancements in Microbial Applications for Sustainable Food Production [J ] . Foods , 2025 , 14 ( 19 ).

JEONG K J . Advancing microbial engineering through synthetic biology [J ] . J Microbiol , 2025 , 63 ( 3 ): e2503100 .

SONG X , WAN W , ZHANG Y , et al . Production of docosahexaenoic acid from corncob residue wastes through integrated whole-cell lignocellulosic saccharification and lipid fermentation by Aurantiochytrium [J ] . Bioresour Technol , 2025 , 431 : 132606 .

LIU F , LU Z , LU T , et al . Metabolic engineering of oleaginous yeast in the lipogenic phase enhances production of nervonic acid [J ] . Metab Eng , 2023 , 80 : 193 - 206 .

BLAZECK J , HILL A , LIU L , et al . Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production [J ] . Nat Commun , 2014 , 5 : 3131 .

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 ( 04 ): 509 - 27 .

XU P . 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 , 2 ( 04 ): 509 - 527 .

LARROUDE M , ROSSIGNOL T , NICAUD J M , et al . Synthetic biology tools for engineering Yarrowia lipolytica [J ] . Biotechnol Adv , 2018 , 36 ( 8 ): 2150 - 64 .

BEOPOULOS A , CESCUT J , HADDOUCHE R , et al . Yarrowia lipolytica as a model for bio-oil production [J ] . Prog Lipid Res , 2009 , 48 ( 6 ): 375 - 87 .

XU J , ZHAO X , DU W , et al . Bioconversion of glycerol into lipids by Rhodosporidium toruloides in a two-stage process and characterization of lipid properties [J ] . Eng Life Sci , 2017 , 17 ( 3 ): 303 - 13 .

YANG X , JIN G , WANG Y , et al . Lipid production on free fatty acids by oleaginous yeasts under non-growth conditions [J ] . Bioresour Technol , 2015 , 193 : 557 - 62 .

LI Y , ZHAO Z K , BAI F . High-density cultivation of oleaginous yeast Rhodosporidium toruloides Y4 in fed-batch culture [J ] . Enzyme and Microbial Technology , 2007 , 41 ( 3 ): 312 - 7 .

LIN J , SHEN H , TAN H , et al . Lipid production by Lipomyces starkeyi cells in glucose solution without auxiliary nutrients [J ] . J Biotechnol , 2011 , 152 ( 4 ): 184 - 8 .

HU C , WU S , WANG Q , et al . Simultaneous utilization of glucose and xylose for lipid production by Trichosporon cutaneum [J ] . Biotechnol Biofuels , 2011 , 4 ( 1 ): 25 .

ZHOU Y J , BUIJS N A , ZHU Z , et al . Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories [J ] . Nature Communications , 2016 , 7 ( 1 ): 11709 .

CHANG L , CHEN H , TANG X , et al . Advances in improving the biotechnological application of oleaginous fungus Mortierella alpina [J ] . Appl Microbiol Biotechnol , 2021 , 105 ( 16-17 ): 6275 - 89 .

OKUDA T , ANDO A , NEGORO H , et al . Eicosapentaenoic acid (EPA) production by an oleaginous fungus Mortierella alpina expressing heterologous the Δ17-desaturase gene under ordinary temperature [J ] . European Journal of Lipid Science and Technology , 2015 , 117 ( 12 ): 1919 - 27 .

RODRIGUES R C E , BENTO H B S , CARVALHO A K F , et al . Critical applications of Mucor circinelloides within a biorefinery context [J ] . Crit Rev Biotechnol , 2019 , 39 ( 4 ): 555 - 70 .

FAZILI A B A , SHAH A M , ZAN X , et al . Mucor circinelloides: a model organism for oleaginous fungi and its potential applications in bioactive lipid production [J ] . Microb Cell Fact , 2022 , 21 ( 1 ): 29 .

ZHANG X Y , LI B , HUANG B C , et al . Production, Biosynthesis, and Commercial Applications of Fatty Acids From Oleaginous Fungi [J ] . Front Nutr , 2022 , 9 : 873657 .

SAINI R K , PRASAD P , SREEDHAR R V , et al . Omega-3 Polyunsaturated Fatty Acids (PUFAs): Emerging Plant and Microbial Sources, Oxidative Stability, Bioavailability, and Health Benefits-A Review [J ] . Antioxidants (Basel) , 2021 , 10 ( 10 ).

孙冠男 , 任路静 , 瞿亮 , et al . 裂殖壶菌单细胞油脂的组分特性分析 [J ] . 中国油脂 , 2013 , 38 ( 06 ): 70 - 3 .

SHEN Y P , CHEN S J , ZHOU X , et al . Advances in biosynthesis of microbial oils in metabolically engineered Yarrowia lipolytica [J ] . China Oils and Fats , 2022 , 47 ( 10 ): 103 - 113 .

KIM H M , CHAE T U , CHOI S Y , et al . Engineering of an oleaginous bacterium for the production of fatty acids and fuels [J ] . Nat Chem Biol , 2019 , 15 ( 7 ): 721 - 9 .

GIENTKA I , GADASZEWSKA M , BŁAŻEJAK S , et al . Evaluation of lipid biosynthesis ability by Rhodotorula and Sporobolomyces strains in medium with glycerol [J ] . European Food Research and Technology , 2017 , 243 ( 2 ): 275 - 86 .

FANG L , HAO X , FAN J , et al . Genome-scale CRISPRi screen identifies pcnB repression conferring improved physiology for overproduction of free fatty acids in Escherichia coli [J ] . Nat Commun , 2025 , 16 ( 1 ): 3060 .

沈玉平 , 陈诗洁 , 周迅 , et al . 代谢工程改造解脂耶氏酵母生产油脂研究进展 [J ] . 中国油脂 , 2022 , 47 ( 10 ): 103 - 13 .

SHEN Y P , CHEN S J , ZHOU X , et al . Advances in biosynthesis of microbial oils in metabolically engineered Yarrowia lipolytica [J ] . China Oils and Fats , 2022 , 47 ( 10 ): 103 - 113 .

SPAGNUOLO M , YAGUCHI A , BLENNER M . Oleaginous yeast for biofuel and oleochemical production [J ] . Curr Opin Biotechnol , 2019 , 57 : 73 - 81 .

YAEGASHI J , KIRBY J , ITO M , et al . Rhodosporidium toruloides: a new platform organism for conversion of lignocellulose into terpene biofuels and bioproducts [J ] . Biotechnol Biofuels , 2017 , 10 : 241 .

YAGUCHI A , ROBINSON A , MIHEALSICK E , et al . Metabolism of aromatics by Trichosporon oleaginosus while remaining oleaginous [J ] . Microb Cell Fact , 2017 , 16 ( 1 ): 206 .

SUNDARAM T , RAJENDRAN S , GNANASEKARAN L , et al . Bioengineering strategies of microalgae biomass for biofuel production: recent advancement and insight [J ] . Bioengineered , 2023 , 14 ( 1 ): 2252228 .

SIVAKUMAR R , SACHIN S , PRIYADARSHINI R , et al . Sustainable production of eicosapentaenoic acid-rich oil from microalgae: Towards an algal biorefinery [J ] . J Appl Microbiol , 2022 , 132 ( 6 ): 4170 - 85 .

HAUSHALTER R W , GROFF D , DEUTSCH S , et al . Development of an orthogonal fatty acid biosynthesis system in E. coli for oleochemical production [J ] . Metab Eng , 2015 , 30 : 1 - 6 .

LUDIG D L , ZHAI X , RITTNER A , et al . Engineering metazoan fatty acid synthase to control chain length applied in yeast [J ] . Nat Chem Biol , 2026 .

FENG Y , WANG Y , LIU J , et al . Structural Insight into Acyl-ACP Thioesterase toward Substrate Specificity Design [J ] . ACS Chem Biol , 2017 , 12 ( 11 ): 2830 - 6 .

JUNG W , KIM E J , HAN S J , et al . Enzymatic modification by point mutation and functional analysis of an omega-6 fatty acid desaturase from Arctic Chlamydomonas sp [J ] . Prep Biochem Biotechnol , 2017 , 47 ( 2 ): 143 - 50 .

WENDEL A A , LEWIN T M , COLEMAN R A . Glycerol-3-phosphate acyltransferases: rate limiting enzymes of triacylglycerol biosynthesis [J ] . Biochim Biophys Acta , 2009 , 1791 ( 6 ): 501 - 6 .

WATCHARAWIPAS A , RUNGUPHAN W , KHAMWACHIRAPITHAK P , et al . Integrating yeast biodiversity and machine learning for predictive metabolic engineering [J ] . FEMS Yeast Res , 2025 , 25 .

GONG X , ZHANG J , GAN Q , et al . Leveraging artificial intelligence for efficient microbial production [J ] . Bioresour Technol , 2026 , 439 : 133286 .

吴柯 , 罗家豪 , 李斐然 , et al . 机器学习驱动的基因组规模代谢模型构建与优化 [J ] . 合成生物学 , 2025 , 6 ( 03 ): 566 - 84 .

WU K , LUO J H , LI F R , et al . Applications of machine learning in the reconstruction and curation of genome-scale metabolic models [J ] . Synthetic Biology Journal , 2025 , 6 ( 03 ): 566 - 584 .

MEDINA-ORTIZ D , KHALIFEH A , ANVARI-KAZEMABAD H , et al . Interpretable and explainable predictive machine learning models for data-driven protein engineering [J ] . Biotechnol Adv , 2025 , 79 : 108495 .

ERICKSON E , GADO J E , AVILáN L , et al . Sourcing thermotolerant poly(ethylene terephthalate) hydrolase scaffolds from natural diversity [J ] . Nat Commun , 2022 , 13 ( 1 ): 7850 .

WANG Y , HAN S , WANG Y , et al . Artificial Intelligence Technology Assists Enzyme Prediction and Rational Design [J ] . J Agric Food Chem , 2025 , 73 ( 12 ): 7065 - 73 .

GREENHALGH J C , FAHLBERG S A , PFLEGER B F , et al . Machine learning-guided acyl-ACP reductase engineering for improved in vivo fatty alcohol production [J ] . Nat Commun , 2021 , 12 ( 1 ): 5825 .

LANDWEHR G M , BOGART J W , MAGALHAES C , et al . Accelerated enzyme engineering by machine-learning guided cell-free expression [J ] . Nat Commun , 2025 , 16 ( 1 ): 865 .

LIU F , ZHAO S B , LIU Y H , et al . Machine learning-driving optimization and spatial assembly of a cell-free system for high-yield liquiritigenin production [J ] . Adv Biotechnol (Singap) , 2026 , 4 ( 2 ).

DU F , LI Z , LI X , et al . Optimizing multicopy chromosomal integration for stable high-performing strains [J ] . Nat Chem Biol , 2024 , 20 ( 12 ): 1670 - 9 .

LI Y , RAO J , JIANG Z , et al . AI-driven engineering of EgtD enabling high-efficiency ergothioneine synthesis with a multi-enzyme cascade [J ] . Int J Biol Macromol , 2025 , 327 ( Pt 1 ): 147266 .

GONG X , ZHANG J , GAN Q , et al . Advancing microbial production through artificial intelligence-aided biology [J ] . Biotechnol Adv , 2024 , 74 : 108399 .

CHOUDHURY S , NARAYANAN B , MORET M , et al . Generative machine learning produces kinetic models that accurately characterize intracellular metabolic states [J ] . Nat Catal , 2024 , 7 ( 10 ): 1086 - 98 .

RAJASEKHAR N , RADHAKRISHNAN T K , MOHAMED S N . Reinforcement learning based temperature control of a fermentation bioreactor for ethanol production [J ] . Biotechnol Bioeng , 2024 , 121 ( 10 ): 3114 - 27 .

LI G , RABE K S , NIELSEN J , et al . Machine Learning Applied to Predicting Microorganism Growth Temperatures and Enzyme Catalytic Optima [J ] . ACS Synth Biol , 2019 , 8 ( 6 ): 1411 - 20 .

ZARETCKII M , BUSLAEV P , KOZLOVSKII I , et al . Approaching Optimal pH Enzyme Prediction with Large Language Models [J ] . ACS Synth Biol , 2024 , 13 ( 9 ): 3013 - 21 .

CHEN H , MA H , YU L , et al . Functional characterization of the plastidial enzyme GPAT in microalgae and its potential role in lipid biosynthesis [J ] . Plant Physiol , 2025 , 199 ( 1 ).

VAN ERP H , BRYANT F M , MARTIN-MORENO J , et al . Engineering the stereoisomeric structure of seed oil to mimic human milk fat [J ] . Proc Natl Acad Sci U S A , 2019 , 116 ( 42 ): 20947 - 52 .

VAN ERP H , BRYANT F M , MARTIN-MORENO J , et al . Production of the infant formula ingredient 1,3-olein-2-palmitin in Arabidopsis thaliana seeds [J ] . Metab Eng , 2021 , 67 : 67 - 74 .

YANG K K , WU Z , ARNOLD F H . Machine-learning-guided directed evolution for protein engineering [J ] . Nat Methods , 2019 , 16 ( 8 ): 687 - 94 .

FEEHAN R , MONTEZANO D , SLUSKY J S G . Machine learning for enzyme engineering, selection and design [J ] . Protein Eng Des Sel , 2021 , 34 .

DYER J M , CHAPITAL D C , KUAN J W , et al . Metabolic engineering of Saccharomyces cerevisiae for production of novel lipid compounds [J ] . Appl Microbiol Biotechnol , 2002 , 59 ( 2-3 ): 224 - 30 .

CHAI T , TAO Y , ZHAO C , et al . Hierarchical metabolic engineering for rewiring cellular metabolism [J ] . FEMS Microbiol Rev , 2025 , 49 .

HU Y , ZHU Z , NIELSEN J , et al . Engineering Saccharomyces cerevisiae cells for production of fatty acid-derived biofuels and chemicals [J ] . Open Biol , 2019 , 9 ( 5 ): 190049 .

MATEI P L , DELEANU I , BREZOIU A M , et al . Ultrasound-Assisted Extraction of Blackberry Seed Oil: Optimization and Oil Characterization [J ] . Molecules , 2023 , 28 ( 6 ).

LIU C , WUFUER A , KONG L , et al . Organic solvent extraction-assisted catalytic hydrothermal liquefaction of algae to bio-oil [J ] . RSC Adv , 2018 , 8 ( 55 ): 31717 - 24 .

EKPENI L E N , BENYOUNIS K Y , NKEM-EKPENI F F , et al . Underlying factors to consider in improving energy yield from biomass source through yeast use on high-pressure homogenizer (hph) [J ] . Energy , 2015 , 81 : 74 - 83 .

GAO Y , DING Z , LIU Y , et al . Aqueous enzymatic extraction: A green, environmentally friendly and sustainable oil extraction technology [J ] . Trends in Food Science & Technology , 2024 , 144 : 104315 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

人工智能驱动合成生物学研究

合成生物制造知识产权保护体系的现状、问题与建议

生物制造新食品原料产业化的机遇、挑战与监管驱动——以麦角硫因为例

生物制造标准体系建设的现状、问题与建议

生物燃料高效生产微生物细胞工厂构建研究进展