Research progress in the biosynthesis of salidroside

HUANG Shuhan; MA He; LUO Yunzi

doi:10.12211/2096-8280.2024-076

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Research progress in the biosynthesis of salidroside

Invited Review | 更新时间：2025-05-20

- Research progress in the biosynthesis of salidroside
- Synthetic Biology Journal Vol. 6, Issue 2, Pages: 391-407(2025)
- 作者机构：
  
  1.天津大学化工学院，教育部合成生物学前沿科学中心，天津 300072
  2.天津大学合成生物技术全国重点实验室，天津 300072
  3.物质绿色创造与制造海河实验室，天津 300192
  4.天津大学佐治亚理工大学深圳学院，广东深圳 518071
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2024-076
  CLC： Q819
- Received：18 October 2024，
  
  Revised：2025-03-09，
  
  Published：30 April 2025
- 稿件说明：
移动端阅览
黄姝涵，马赫，罗云孜. 生物合成红景天苷的研究进展［J］. 合成生物学， 2025， 6（2）： 391-407

HUANG Shuhan， MA He， LUO Yunzi. Research progress in the biosynthesis of salidroside［J］. Synthetic Biology Journal， 2025， 6（2）： 391-407
黄姝涵，马赫，罗云孜. 生物合成红景天苷的研究进展［J］. 合成生物学， 2025， 6（2）： 391-407 DOI： 10.12211/2096-8280.2024-076.

HUANG Shuhan， MA He， LUO Yunzi. Research progress in the biosynthesis of salidroside［J］. Synthetic Biology Journal， 2025， 6（2）： 391-407 DOI： 10.12211/2096-8280.2024-076.

摘要

红景天苷是一种具有抗缺氧、抗氧化、抗衰老和抗肿瘤等活性的天然产物，被广泛应用于化妆品与医药领域。目前获取红景天苷的主要方式是从红景天属植物的根茎和块茎中提取，由于其含量稀少，日益增长的市场需求导致植物资源逐渐匮乏。因此，开发新的合成方法成为了研究热点。红景天苷的天然生物合成路径已被解析，随着合成生物学的发展，采用合成生物技术构建微生物细胞工厂合成红景天苷成为缓解当前供需失衡和资源紧缺状况的有效途径。本文针对红景天苷的药理活性、植物合成路径、途径酶的挖掘与筛选、大肠杆菌和酿酒酵母的生物合成现状等相关研究进展进行系统性的综述，探讨了红景天苷的分离提纯方法以及它作为合成中间体在制备其他化合物方面的应用潜力，以期助力对红景天苷合成路径与相关工程改造策略的理解，并推动红景天苷绿色、高效的生物合成。

Abstract

Salidroside

a natural product known for its anti-hypoxia

anti-oxidation

anti-inflammatory

anti-aging

and anti-tumor properties

is extensively utilized in the food

cosmetics and pharmaceutical industries. Traditionally

salidroside has been obtained through the extraction from the rhizomes and tubers of

Rhodiola

species

including water extraction

two-phase aqueous extraction

supercritical CO

extraction and microwave assisted extraction. However

its low natural abundance (with the salidroside content in rhizomes and tubers of

Rhodiola

species ranging from 0.5% to 0.8%)

coupled with escalating demand

has led to a progressive depletion of these plant resources. Given the broad application potential of salidroside

the rapid growth of market demand

and the increasing scarcity of natural resources

there is an urgent need to develop innovative synthetic approaches for this valuable compound. Chemical synthesis of salidroside is characterized by its efficiency and rapid processing time. However

the use of strong acids

bases

and catalysts with heavy metal ions in the synthesis process poses challenges for the separation of salidroside with environmental risks. In recent years

with the advancements in synthetic biology

the construction of microbial cell factories for the biosynthesis of salidroside has become a viable strategy for addressing the current supply-demand imbalance and resource scarcity associated with the natural biosynthetic pathway of salidroside. To enhance the production of salidroside biosynthesis

two major strategies can be employed. F

irst

metabolic engineering approaches can be used to overexpress key genes in the synthesis pathways while knocking out or downregulating the expression of genes related to the bypass routes

thereby increasing precursor accumulation and enhancing the metabolic flux. Second

enzyme engineering can be applied to improve the catalytic efficiency and regioselectivity of natural glycosyltransferases

which often exhibit low activity and poor selectivity. Sequence alignment techniques can be used to identify and screen potential glycosyltransferases from various biological genomes. Additionally

protein engineering combined with computational approaches can be utilized to optimize these enzymes to meet specific requirements

ultimately improving the production of salidroside. In this comprehensive review

we systematically assess the pharmacological activities of salidroside

the plant biosynthetic pathway

the mining and screening of the enzymes

and the biosynthetic advancements in

Escherichia coli

and

Saccharomyces cerevisiae

. Additionally

we discuss the separation and purification methods of salidroside and its application potential as a synthetic intermediate in the preparation of other compounds

such as hydroxysalidroside

verbascoside and echinacoside. This review aims to enhance the understanding of the biosynthetic pathway of salidroside

thereby promoting a greener and more efficient biosynthetic approach to salidroside production.

关键词

Keywords

references

PRZYBYŁ J L , WĘGLARZ Z , GESZPRYCH A . Quality of Rhodiola rosea cultivated in Poland [J ] . Acta Horticulturae , 2008 ( 765 ): 143 - 150 .

TASHEVA K , KOSTURKOVA G . Bulgarian golden root in vitro cultures for micropropagation and reintroduction [J ] . Central European Journal of Biology , 2010 , 5 ( 6 ): 853 - 863 .

WĘGLARZ Z , PRZYBYŁ J L , GESZPRYCH A . Roseroot ( Rhodiola rosea L.): effect of internal and external factors on accumulation of biologically active compounds [M/OL ] // RAMAWAT K , MERILLON, J . Bioactive molecules and medicinal plants. Springer: Berlin, Heidelberg , 2008 : 297 - 315 [2024-07-01] . https://doi.org/10.1007/978-3-540-74603-4_16 https://doi.org/10.1007/978-3-540-74603-4_16 .

XIONG Y L , WANG Y M , XIONG Y L , et al . Protective effect of salidroside on hypoxia-related liver oxidative stress and inflammation via Nrf2 and JAK2/STAT3 signaling pathways [J ] . Food Science & Nutrition , 2021 , 9 ( 9 ): 5060 - 5069 .

LIU Q , CHEN J Z , ZENG A Q , et al . Pharmacological functions of salidroside in renal diseases: facts and perspectives [J ] . Frontiers in Pharmacology , 2024 , 14 : 1309598 .

ZHANG X M , XIE L , LONG J Y , et al . Salidroside: a review of its recent advances in synthetic pathways and pharmacological properties [J ] . Chemico-Biological Interactions , 2021 , 339 : 109268 .

XU Z W , CHEN X , JIN X H , et al . SILAC-based proteomic analysis reveals that salidroside antagonizes cobalt chloride-induced hypoxic effects by restoring the tricarboxylic acid cycle in cardiomyocytes [J ] . Journal of Proteomics , 2016 , 130 : 211 - 220 .

CHEN X P , KOU Y B , LU Y S , et al . Salidroside ameliorated hypoxia-induced tumorigenesis of BxPC-3 cells via downregulating hypoxia-inducible factor (HIF)-1α and LOXL2 [J ] . Journal of Cellular Biochemistry , 2020 , 121 ( 1 ): 165 - 173 .

PAN C L , DAI G L , ZHANG H W , et al . Salidroside ameliorates orthopedic surgery-induced cognitive dysfunction by activating adenosine 5′-monophosphate-activated protein kinase signaling in mice [J ] . European Journal of Pharmacology , 2022 , 929 : 175148 .

LAI W F , LUO R , TANG Y H , et al . Salidroside directly activates HSC70, revealing a new role for HSC70 in BDNF signalling and neurogenesis after cerebral ischemia [J ] . Phytotherapy Research , 2024 , 38 ( 6 ): 2619 - 2640 .

SHI T Y , CHEN H , JING L L , et al . Development of a kilogram-scale synthesis of salidroside and its analogs [J ] . Synthetic Communications , 2011 , 41 ( 17 ): 2594 - 2600 .

TROSHCHENKO A T , YUODVIRSHIS A M . Synthesis of glycosides of 2-( p -hydroxyphenyl)ethanol (tyrosol) [J ] . Chemistry of Natural Compounds , 1969 , 5 ( 4 ): 217 - 220 .

史明明 . 红景天苷的合成方法研究 [D ] . 长沙 : 湖南师范大学 , 2012 .

SHI M M . Study on synthetic methods of salidroside [D ] . Changsha : Hunan Normal University , 2012 .

JIANG J J , YIN H , WANG S , et al . Metabolic engineering of Saccharomyces cerevisiae for high-level production of salidroside from glucose [J ] . Journal of Agricultural and Food Chemistry , 2018 , 66 ( 17 ): 4431 - 4438 .

LI Y Z , WU A P , WANG D D , et al . Salidroside attenuates oxygen and glucose deprivation-induced neuronal injury by inhibiting ferroptosis [J ] . Asian Pacific Journal of Tropical Biomedicine , 2023 , 13 ( 2 ): 70 - 79 .

LIU Y J , WANG J Y , WANG L , et al . Biosynthesis and biotechnological production of salidroside from Rhodiola genus plants [J ] . Phytochemistry Reviews , 2022 , 21 ( 5 ): 1605 - 1626 .

BERNATONIENE J , JAKSTAS V , KOPUSTINSKIENE D M . Phenolic compounds of Rhodiola rosea L. as the potential alternative therapy in the treatment of chronic diseases [J ] . International Journal of Molecular Sciences , 2023 , 24 ( 15 ): 12293 .

YAO Y Y , REN Z C , YANG R H , et al . Salidroside reduces neuropathology in Alzheimer’s disease models by targeting NRF2/SIRT3 pathway [J ] . Cell & Bioscience , 2022 , 12 ( 1 ): 180 .

LI L P , FU W L , WANG J , et al . Salidroside improves cellular senescence in COPD by inhibiting the JAK2/STAT3 pathway [J ] . Journal of Biological Regulators and Homeostatic Agents , 2024 , 38 ( 5 ): 4415 - 4426 .

KIM K J , JUNG Y S , YOU D M , et al . Neuroprotective effects of ethanolic extract from dry Rhodiola rosea L. rhizomes [J ] . Food Science and Biotechnology , 2021 , 30 ( 2 ): 287 - 297 .

DING X R , WANG W L , CHEN J W , et al . Salidroside protects inner ear hair cells and spiral ganglion neurons from manganese exposure by regulating ROS levels and inhibiting apoptosis [J ] . Toxicology Letters , 2019 , 310 : 51 - 60 .

LIU B , WEI H L , LAN M , et al . microRNA-21 mediates the protective effects of salidroside against hypoxia/reoxygenation-induced myocardial oxidative stress and inflammatory response [J ] . Experimental and Therapeutic Medicine , 2020 , 19 ( 3 ): 1655 - 1664 .

LUO X P , LIAO H , PENG J , et al . Salidroside protects chondrocytes against IL-1β-induced injury and alleviates osteoarthritis progression by activating the Nrf2 pathway [J ] . Discovery Medicine , 2024 , 36 ( 181 ): 266 - 277 .

LIU S S , YU X W , HU B J , et al . Salidroside rescued mice from experimental sepsis through anti-inflammatory and anti-apoptosis effects [J ] . Journal of Surgical Research , 2015 , 195 ( 1 ): 277 - 283 .

MAO G X , DENG H B , YUAN L G , et al . Protective role of salidroside against aging in a mouse model induced by D-galactose [J ] . Biomedical and Environmental Sciences , 2010 , 23 ( 2 ): 161 - 166 .

RAMASAMY R , VANNUCCI S J , YAN S S D , et al . Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation [J ] . Glycobiology , 2005 , 15 ( 7 ): 16 R-28R.

ALIKHANI M , MACLELLAN C M , RAPTIS M , et al . Advanced glycation end products induce apoptosis in fibroblasts through activation of ROS, MAP kinases, and the FOXO1 transcription factor [J ] . American Journal of Physiology Cell Physiology , 2007 , 292 ( 2 ): C850 - C856 .

BUCALA R , CERAMI A . Advanced glycosylation: chemistry, biology, and implications for diabetes and aging [J ] . Advances in Pharmacology , 1992 , 23 : 1 - 34 .

MAO G X , WANG Y , QIU Q , et al . Salidroside protects human fibroblast cells from premature senescence induced by H 2 O 2 partly through modulating oxidative status [J ] . Mechanisms of Ageing and Development , 2010 , 131 ( 11/12 ): 723 - 731 .

QIAN E W , GE D T , KONG S K . Salidroside promotes erythropoiesis and protects erythroblasts against oxidative stress by up-regulating glutathione peroxidase and thioredoxin [J ] . Journal of Ethnopharmacology , 2011 , 133 ( 2 ): 308 - 314 .

ZHONG X Y , LIN R H , LI Z F , et al . Effects of salidroside on cobalt chloride-induced hypoxia damage and mTOR signaling repression in PC12 cells [J ] . Biological & Pharmaceutical Bulletin , 2014 , 37 ( 7 ): 1199 - 1206 .

陈努菊 . 一种红景天保湿抗衰乳 : CN108309915A [P ] . 2018-07-24 .

CHEN N J . Rhodiola rosea moisture-preserving anti-aging lotion : CN108309915A [P ] . 2018-07-24 .

LU H , LI Y , ZHANG T , et al . Salidroside reduces high-glucose-induced podocyte apoptosis and oxidative stress via upregulating heme oxygenase-1 (HO-1) expression [J ] . Medical Science Monitor , 2017 , 23 : 4067 - 4076 .

LIN S Y , DAN X , DU X X , et al . Protective effects of salidroside against carbon tetrachloride (CCl 4 )-induced liver injury by initiating mitochondria to resist oxidative stress in mice [J ] . International Journal of Molecular Sciences , 2019 , 20 ( 13 ): 3187 .

XING S S , YANG X Y , LI W J , et al . Salidroside stimulates mitochondrial biogenesis and protects against H 2 O 2 -induced endothelial dysfunction [J ] . Oxidative Medicine and Cellular Longevity , 2014 , 2014 ( 1 ): 904834 .

黎明华 , 汤长发 , 欧阳江琼 . 红景天苷对运动后自由基和能量代谢改变的影响 [J ] . 中国应用生理学杂志 , 2012 , 28 ( 1 ): 53 - 56 .

LI M H , TANG C F , OUYANG J Q . Influence of salidroside from Rhodiola sachalinensis A. Bor on some related indexes of free radical and energy metabolism after exercise in mice [J ] . Chinese Journal of Applied Physiology , 2012 , 28 ( 1 ): 53 - 56 .

胥鑫萌 , 王文权 , 孙洁怡 , 等 . 红景天苷在日化领域中的研究进展 [J ] . 中国洗涤用品工业 , 2020 ( 12 ): 74 - 79 .

XU X M , WANG W Q , SUN J Y , et al . Research progress of salidroside in daily chemical field [J ] . China Cleaning Industry , 2020 ( 12 ): 74 - 79 .

FAN X J , WANG Y , WANG L , et al . Salidroside induces apoptosis and autophagy in human colorectal cancer cells through inhibition of PI3K/Akt/mTOR pathway [J ] . Oncology Reports , 2016 , 36 ( 6 ): 3559 - 3567 .

HU X L , ZHANG X Q , QIU S F , et al . Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells [J ] . Biochemical and Biophysical Research Communications , 2010 , 398 ( 1 ): 62 - 67 .

LIU Z B , LI X S , SIMONEAU A R , et al . Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy [J ] . Molecular Carcinogenesis , 2012 , 51 ( 3 ): 257 - 267 .

RONG L , LI Z D , LENG X , et al . Salidroside induces apoptosis and protective autophagy in human gastric cancer AGS cells through the PI3K/Akt/mTOR pathway [J ] . Biomedicine & Pharmacotherapy , 2020 , 122 : 109726 .

HAO W W , LI N , MI C F , et al . Salidroside attenuates cardiac dysfunction in a rat model of diabetes [J ] . Diabetic Medicine , 2022 , 39 ( 3 ): e14683 .

GE Y L , ZHANG B , SONG J B , et al . Discovery of salidroside as a novel non-coding RNA modulator to delay cellular senescence and promote BK-dependent apoptosis in cerebrovascular smooth muscle cells of simulated microgravity rats [J ] . International Journal of Molecular Sciences , 2023 , 24 ( 19 ): 14531 .

XU N , HUANG F , JIAN C D , et al . Neuroprotective effect of salidroside against central nervous system inflammation-induced cognitive deficits: a pivotal role of sirtuin 1-dependent Nrf-2/HO-1/NF-κB pathway [J ] . Phytotherapy Research , 2019 , 33 ( 5 ): 1438 - 1447 .

YANG S X , WANG L S , ZENG Y , et al . Salidroside alleviates cognitive impairment by inhibiting ferroptosis via activation of the Nrf2/GPX4 axis in SAMP8 mice [J ] . Phytomedicine , 2023 , 114 : 154762 .

HEMWIMOL S , PAVASANT P , SHOTIPRUK A . Ultrasound-assisted extraction of anthraquinones from roots of Morinda citrifolia [J ] . Ultrasonics Sonochemistry , 2006 , 13 ( 6 ): 543 - 548 .

MAO Y , LI Y , YAO N . Simultaneous determination of salidroside and tyrosol in extracts of Rhodiola L. by microwave assisted extraction and high-performance liquid chromatography [J ] . Journal of Pharmaceutical and Biomedical Analysis , 2007 , 45 ( 3 ): 510 - 515 .

ĐUROVIĆ S , NIKOLIĆ B , LUKOVIĆ N , et al . The impact of high-power ultrasound and microwave on the phenolic acid profile and antioxidant activity of the extract from yellow soybean seeds [J ] . Industrial Crops and Products , 2018 , 122 : 223 - 231 .

ZHANG Y F , ZHOU Z L , ZOU L , et al . Imidazolium-based ionic liquids with inorganic anions in the extraction of salidroside and tyrosol from Rhodiola : the role of cations and anions on the extraction mechanism [J ] . Journal of Molecular Liquids , 2019 , 275 : 136 - 145 .

LI F J , YUAN Y , LI H , et al . Infrared-assisted extraction of salidroside from the root of Rhodiola crenulata with a novel ionic liquid that dissolves cellulose [J ] . RSC Advances , 2015 , 5 ( 59 ): 47326 - 47333 .

HU B , ZHOU K , LIU Y T , et al . Optimization of microwave-assisted extraction of oil from tiger nut ( Cyperus esculentus L.) and its quality evaluation [J ] . Industrial Crops and Products , 2018 , 115 : 290 - 297 .

GÓMEZ A V , TADINI C C , BISWAS A , et al . Microwave-assisted extraction of soluble sugars from banana puree with natural deep eutectic solvents (NADES) [J ] . LWT , 2019 , 107 : 79 - 88 .

GYÖRGY Z , TOLONEN A , NEUBAUER P , et al . Enhanced biotransformation capacity of Rhodiola rosea callus cultures for glycosid production [J ] . Plant Cell, Tissue and Organ Culture , 2005 , 83 ( 2 ): 129 - 135 .

RATTAN S , KUMAR A , KUMAR D , et al . Enhanced production of phenylethanoids mediated through synergistic approach of precursor feeding and light regime in cell suspension culture of Rhodiola imbricata (Edgew.) [J ] . Applied Biochemistry and Biotechnology , 2022 , 194 ( 7 ): 3242 - 3260 .

XU J F , LIU C B , HAN A M , et al . Strategies for the improvement of salidroside production in cell suspension cultures of Rhodiola sachalinensis [J ] . Plant Cell Reports , 1998 , 17 ( 4 ): 288 - 293 .

WU S X , ZU Y G , WU M . High yield production of salidroside in the suspension culture of Rhodiola sachalinensis [J ] . Journal of Biotechnology , 2003 , 106 ( 1 ): 33 - 43 .

RATTAN S , WARGHAT A R . Integration of biotechnological approaches for the production of phenylethanoids and phenylpropanoids in in vitro cultures of Rhodiola sp. a comprehensive review [J ] . Industrial Crops and Products , 2023 , 206 : 117625 .

XIE H , SHEN C Y , JIANG J G . The sources of salidroside and its targeting for multiple chronic diseases [J ] . Journal of Functional Foods , 2020 , 64 : 103648 .

XU J F , SU Z G , FENG P S . Activity of tyrosol glucosyltransferase and improved salidroside production through biotransformation of tyrosol in Rhodiola sachalinensis cell cultures [J ] . Journal of Biotechnology , 1998 , 61 ( 1 ): 69 - 73 .

TORRENS-SPENCE M P , PLUSKAL T , LI F S , et al . Complete pathway elucidation and heterologous reconstitution of Rhodiola salidroside biosynthesis [J ] . Molecular Plant , 2018 , 11 ( 1 ): 205 - 217 .

CHUNG D , KIM S Y , AHN J H . Production of three phenylethanoids, tyrosol, hydroxytyrosol, and salidroside, using plant genes expressing in Escherichia coli [J ] . Scientific Reports , 2017 , 7 ( 1 ): 2578 .

GRECH-BARAN M , SYKŁOWSKA-BARANEK K , PIETROSIUK A . Biotechnological approaches to enhance salidroside, rosin and its derivatives production in selected Rhodiola spp. in vitro cultures [J ] . Phytochemistry Reviews , 2015 , 14 ( 4 ): 657 - 674 .

IACOMETTI C , MARX K , HÖNICK M , et al . Activating silent glycolysis bypasses in Escherichia coli [J ] . BioDesign Research , 2022 , 2022 : 9859643 .

ROSTAIN W , SHEN S S , CORDERO T , et al . Engineering a circular riboregulator in Escherichia coli [J ] . BioDesign Research , 2020 , 2020 : 1916789 .

PARK S Y , YANG D S , HA S H , et al . Metabolic engineering of microorganisms for the production of natural compounds [J ] . Advanced Biosystems , 2018 , 2 ( 1 ): 1700190 .

LEE S Y . High cell-density culture of Escherichia coli [J ] . Trends in Biotechnology , 1996 , 14 ( 3 ): 98 - 105 .

YANG D , PARK S Y , PARK Y S , et al . Metabolic engineering of Escherichia coli for natural product biosynthesis [J ] . Trends in Biotechnology , 2020 , 38 ( 7 ): 745 - 765 .

BRÜSSOW H , CANCHAYA C , HARDT W D . Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion [J ] . Microbiology and Molecular Biology Reviews , 2004 , 68 ( 3 ): 560 - 602 , tableofcontents.

CORNELIS P . Expressing genes in different Escherichia coli compartments [J ] . Current Opinion in Biotechnology , 2000 , 11 ( 5 ): 450 - 454 .

PALMELA C , CHEVARIN C , XU Z L , et al . Adherent-invasive Escherichia coli in inflammatory bowel disease [J ] . Gut , 2018 , 67 ( 3 ): 574 - 587 .

PUTIGNANI L , MASSA O , ALISI A . Engineered Escherichia coli as new source of flavonoids and terpenoids [J ] . Food Research International , 2013 , 54 ( 1 ): 1084 - 1095 .

HAMMER S K , AVALOS J L . Harnessing yeast organelles for metabolic engineering [J ] . Nature Chemical Biology , 2017 , 13 ( 8 ): 823 - 832 .

WAGNER J M , ALPER H S . Synthetic biology and molecular genetics in non-conventional yeasts: current tools and future advances [J ] . Fungal Genetics and Biology , 2016 , 89 : 126 - 136 .

BLOUNT B A , WEENINK T , ELLIS T . Construction of synthetic regulatory networks in yeast [J ] . FEBS Letters , 2012 , 586 ( 15 ): 2112 - 2121 .

NIELSEN J , LARSSON C , VAN MARIS A , et al . Metabolic engineering of yeast for production of fuels and chemicals [J ] . Current Opinion in Biotechnology , 2013 , 24 ( 3 ): 398 - 404 .

蒋慧慧 , 王强 , 饶志明 , 等 . 酿酒酵母启动子工程研究进展 [J ] . 中国生物工程杂志 , 2023 , 43 ( 11 ): 78 - 91 .

JIANG H H , WANG Q , RAO Z M , et al . Research progress of the promoter engineering in Saccharomyces cerevisiae [J ] . China Biotechnology , 2023 , 43 ( 11 ): 78 - 91 .

THAK E J , YOO S J , MOON H Y , et al . Yeast synthetic biology for designed cell factories producing secretory recombinant proteins [J ] . FEMS Yeast Research , 2020 , 20 ( 2 ): foaa009 .

XUE Y X , CHEN X Z , YANG C , et al . Engineering Eschericha coli for enhanced tyrosol production [J ] . Journal of Agricultural and Food Chemistry , 2017 , 65 ( 23 ): 4708 - 4714 .

YANG C , CHEN X Z , CHANG J Z , et al . Reconstruction of tyrosol synthetic pathways in Escherichia coli [J ] . Chinese Journal of Chemical Engineering , 2018 , 26 ( 12 ): 2615 - 2621 .

SHEN N , SATOH Y , KOMA D , et al . Optimization of tyrosol-producing pathway with tyrosine decarboxylase and tyramine oxidase in high-tyrosine-producing Escherichia coli [J ] . Journal of Bioscience and Bioengineering , 2024 , 137 ( 2 ): 115 - 123 .

沈玉平 , 周紫微 , 贺茜 , 等 . 群体感应动态调控促进大肠杆菌合成酪醇 [J ] . 生物工程学报 , 2023 , 39 ( 8 ): 3379 - 3393 .

SHEN Y P , ZHOU Z W , HE X , et al . Dynamic regulation using a quorum-sensing circuit enhances the production of tyrosol by Escherichia coli [J ] . Chinese Journal of Biotechnology , 2023 , 39 ( 8 ): 3379 - 3393 .

XUE F Y , GUO H L , HU Y Y , et al . Expression of Codon -optimized plant glycosyltransferase UGT72B14 in Escherichia coli enhances salidroside production [J ] . BioMed Research International , 2016 , 2016 ( 1 ): 9845927 .

BAI Y F , BI H P , ZHUANG Y B , et al . Production of salidroside in metabolically engineered Escherichia coli [J ] . Scientific Reports , 2014 , 4 : 6640 .

FAN B , CHEN T Y , ZHANG S , et al . Mining of efficient microbial UDP-glycosyltransferases by motif evolution cross plant kingdom for application in biosynthesis of salidroside [J ] . Scientific Reports , 2017 , 7 ( 1 ): 463 .

魏晨昱 , 黄珠莹 , 沈知行 , 等 . 基于尿苷二磷酸葡萄糖循环再生系统高效转化酪醇合成红景天苷 [J ] . 生物工程学报 , 2024 , 40 ( 9 ): 3127 - 3141 .

WEI C Y , HUANG Z Y , SHEN Z X , et al . Efficient synthesis of salidroside from tyrosol based on UDPG recycling system [J ] . Chinese Journal of Biotechnology , 2024 , 40 ( 9 ): 3127 - 3141 .

LIU S S , XIA Y Y , YANG H Q , et al . Rational chromosome engineering of Escherichia coli for overproduction of salidroside [J ] . Biochemical Engineering Journal , 2022 , 184 : 108474 .

ZENG W Z , WANG H J , CHEN J B , et al . Engineering Escherichia coli for efficient de novo synthesis of salidroside [J ] . Journal of Agricultural and Food Chemistry , 2024 , 72 ( 51 ): 28369 - 28377 .

KALLSCHEUER N , MENEZES R , FOITO A , et al . Identification and microbial production of the raspberry phenol salidroside that is active against Huntington’s disease [J ] . Plant Physiology , 2019 , 179 ( 3 ): 969 - 985 .

LIU H Y , TIAN Y J , ZHOU Y , et al . Multi-modular engineering of Saccharomyces cerevisiae for high-titre production of tyrosol and salidroside [J ] . Microbial Biotechnology , 2021 , 14 ( 6 ): 2605 - 2616 .

GUO W , HUANG Q L , FENG Y H , et al . Rewiring central carbon metabolism for tyrosol and salidroside production in Saccharomyces cerevisiae [J ] . Biotechnology and Bioengineering , 2020 , 117 ( 8 ): 2410 - 2419 .

LIU H Y , XIAO Q J , WU X X , et al . Mechanistic investigation of a D to N mutation in DAHP synthase that dictates carbon flux into the shikimate pathway in yeast [J ] . Communications Chemistry , 2023 , 6 ( 1 ): 152 .

CUI J L , GUO T T , CHAO J B , et al . Potential of the endophytic fungus Phialocephala fortinii Rac56 found in Rhodiola plants to produce salidroside and p -tyrosol [J ] . Molecules , 2016 , 21 ( 4 ): 502 .

ZHOU X J , ZHANG X X , WANG D , et al . Efficient biosynthesis of salidroside via artificial in vivo enhanced UDP-glucose system using cheap sucrose as substrate [J ] . ACS Omega , 2024 , 9 ( 20 ): 22386 - 22397 .

LIU X , LI X B , JIANG J L , et al . Convergent engineering of syntrophic Escherichia coli coculture for efficient production of glycosides [J ] . Metabolic Engineering , 2018 , 47 : 243 - 253 .

BORNEMAN A R , PRETORIUS I S , CHAMBERS P J . Comparative genomics: a revolutionary tool for wine yeast strain development [J ] . Current Opinion in Biotechnology , 2013 , 24 ( 2 ): 192 - 199 .

GOU Y W , LI D F , ZHAO M H , et al . Intein-mediated temperature control for complete biosynthesis of sanguinarine and its halogenated derivatives in yeast [J ] . Nature Communications , 2024 , 15 ( 1 ): 5238 .

CHEN R B , GAO J Q , YU W , et al . Engineering cofactor supply and recycling to drive phenolic acid biosynthesis in yeast [J ] . Nature Chemical Biology , 2022 , 18 ( 5 ): 520 - 529 .

WANG X Q , YUAN B , ZHANG F L , et al . Novel roles of the greatwall kinase Rim15 in yeast oxidative stress tolerance through mediating antioxidant systems and transcriptional regulation [J ] . Antioxidants , 2024 , 13 ( 3 ): 260 .

GAO D , LIU T F , GAO J C , et al . De novo biosynthesis of vindoline and catharanthine in Saccharomyces cerevisiae [J ] . BioDesign Research , 2022 , 2022 : 2 .

DA SILVA N A , SRIKRISHNAN S . Introduction and expression of genes for metabolic engineering applications in Saccharomyces cerevisiae [J ] . FEMS Yeast Research , 2012 , 12 ( 2 ): 197 - 214 .

KRIVORUCHKO A , SIEWERS V , NIELSEN J . Opportunities for yeast metabolic engineering: lessons from synthetic biology [J ] . Biotechnology Journal , 2011 , 6 ( 3 ): 262 - 276 .

SIDDIQUI M S , THODEY K , TRENCHARD I , et al . Advancing secondary metabolite biosynthesis in yeast with synthetic biology tools [J ] . FEMS Yeast Research , 2012 , 12 ( 2 ): 144 - 170 .

ZHANG Q S , CAO H . Expression of chitosanase from Aspergillus fumigatus chitosanase in Saccharomyces cerevisiae by CRISPR-Cas9 tools [J ] . Bioresources and Bioprocessing , 2024 , 11 ( 1 ): 20 .

HAZELWOOD L A , DARAN J M , VAN MARIS A J A , et al . The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism [J ] . Applied and Environmental Microbiology , 2008 , 74 ( 8 ): 2259 - 2266 .

KÖNIG V , PFEIL A , BRAUS G H , et al . Substrate and metal complexes of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Saccharomyces cerevisiae provide new insights into the catalytic mechanism [J ] . Journal of Molecular Biology , 2004 , 337 ( 3 ): 675 - 690 .

SUÁSTEGUI M , GUO W H , FENG X Y , et al . Investigating strain dependency in the production of aromatic compounds in Saccharomyces cerevisiae [J ] . Biotechnology and Bioengineering , 2016 , 113 ( 12 ): 2676 - 2685 .

CUI J L , GUO T T , REN Z X , et al . Diversity and antioxidant activity of culturable endophytic fungi from alpine plants of Rhodiola crenulata, R. angusta , and R. sachalinensis [J ] . PLoS One , 2015 , 10 ( 3 ): e0118204 .

杨欣 , 曾宪军 , 丁仁芳 , 等 . 一株红景天内生细菌的筛选及初步研究 [J ] . 微生物学通报 , 2015 , 42 ( 10 ): 1962 - 1970 .

YANG X , ZENG X J , DING R F , et al . Screening and preliminary study on one endophytic bacterium of Rhodiola crenulata [J ] . Microbiology China , 2015 , 42 ( 10 ): 1962 - 1970 .

郭勇 , 崔森 . 红景天苷药理作用及机制的研究进展 [J ] . 临床医学进展 , 2022 , 12 ( 8 ): 7202 - 7207 .

GUO Y , CUI S . Research progress on the pharmacological effects and mechanisms of salidroside [J ] . Advances in Clinical Medicine , 2022 , 12 ( 8 ): 7202 - 7207 .

LAI Y M , CHEN H F , LIU L R , et al . Engineering a synthetic pathway for tyrosol synthesis in Escherichia coli [J ] . ACS Synthetic Biology , 2022 , 11 ( 1 ): 441 - 447 .

ALIPIEVA K , KORKINA L , ORHAN I E , et al . Verbascoside: a review of its occurrence, (bio)synthesis and pharmacological significance [J ] . Biotechnology Advances , 2014 , 32 ( 6 ): 1065 - 1076 .

GEORGIEV M , PASTORE S , LULLI D , et al . Verbascum xan thophoeniceum-derived phenylethanoid glycosides are potent inhibitors of inflammatory chemokines in dormant and interferon-gamma-stimulated human keratinocytes [J ] . Journal of Ethnopharmacology , 2012 , 144 ( 3 ): 754 - 760 .

WU P T , LV Q G , WANG S , et al . Using a dual-disease target mapping network pharmacology approach, verbascoside ameliorates osteoporosis by activating estrogen signaling to alleviate oxidative stress [J ] . Combinatorial Chemistry & High Throughput Screening , 2024 .

LU R R , ZHANG L , WANG H H , et al . Echinacoside exerts antidepressant-like effects through enhancing BDNF-CREB pathway and inhibiting neuroinflammation via regulating microglia M1/M2 polarization and JAK1/STAT3 pathway [J ] . Frontiers in Pharmacology , 2023 , 13 : 993483 .

CHEN Y , LI Y Q , FANG J Y , et al . Establishment of the concurrent experimental model of osteoporosis combined with Alzheimer’s disease in rat and the dual-effects of echinacoside and acteoside from Cistanche tubulosa [J ] . Journal of Ethnopharmacology , 2020 , 257 : 112834 .

LIANG Y , CHEN C , XIA B M , et al . Neuroprotective effect of echinacoside in subacute mouse model of Parkinson’s disease [J ] . BioMed Research International , 2019 , 2019 ( 1 ): 4379639 .

GAI X Y , LIN P C , HE Y F , et al . Echinacoside prevents hypoxic pulmonary hypertension by regulating the pulmonary artery function [J ] . Journal of Pharmacological Sciences , 2020 , 144 ( 4 ): 237 - 244 .

DING L , YE H , GU L D , et al . Echinacoside alleviates cognitive impairment in cerebral ischemia rats through α 7nAChR-induced autophagy [J ] . Chinese Journal of Integrative Medicine , 2022 , 28 ( 9 ): 809 - 816 .

WEI W , LAN X B , LIU N , et al . Echinacoside alleviates hypoxic-ischemic brain injury in neonatal rat by enhancing antioxidant capacity and inhibiting apoptosis [J ] . Neurochemical Research , 2019 , 44 ( 7 ): 1582 - 1592 .

CHOO H J , KIM E J , KIM S Y , et al . Microbial synthesis of hydroxytyrosol and hydroxysalidroside [J ] . Applied Biological Chemistry , 2018 , 61 ( 3 ): 295 - 301 .

YANG Y H , XI D Y , WU Y N , et al . Complete biosynthesis of the phenylethanoid glycoside verbascoside [J ] . Plant Communications , 2023 , 4 ( 4 ): 100592 .

XU F X , CAO H , CUI X W , et al . Optimization of fermentation condition for echinacoside yield improvement with Penicillium sp. H1, an endophytic fungus isolated from Ligustrum lucidum Ait using response surface methodology [J ] . Molecules , 2018 , 23 ( 10 ): 2586 .

BAI P G , YANG Y H , TANG J , et al . High-level sustainable production of complex phenylethanoid glycosides from glucose through engineered yeast cell factories [J ] . Metabolic Engineering , 2025 , 87 : 95 - 108 .

李彤 , 杨雅茹 , 闵清 , 等 . 红景天苷提取、含量测定及药理作用研究进展 [J ] . 药物化学 , 2022 ( 2 ): 190 - 197 .

LI T , YANG Y R , MIN Q , et al . Extraction, determination and pharmacological action of salidroside [J ] . Hans Journal of Medicinal Chemistry , 2022 ( 2 ): 190 - 197 .

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