Enabling technology for the biosynthesis of cosmetic raw materials in Saccharomyces cerevisiae

doi:10.12211/2096-8280.2024-070

Abstract

Abstract:

With the rapid growth of consumer demand for cosmetics, the market for cosmetic raw materials is expanding correspondingly. As the core ingredients, cosmetic raw materials not only drive the main efficacy and product competitiveness but are also crucial for ensuring safety. Synthetic biology, an emerging interdisciplinary field based on engineering principles, leverages gene editing, computer simulation, and bioengineering technologies to design, modify, and even resynthesize organisms in a targeted manner. With the continuous development of synthetic biology, Saccharomyces cerevisiae, an important microbial platform, is increasingly used in the production of cosmetic raw materials. Constructing S. cerevisiae cell factories for the heterologous biosynthesis of cosmetic ingredients presents an eco-friendly and sustainable alternative to traditional plant extraction and chemical synthesis methods, addressing both environmental concerns and resource dependence. In this article, we review the development of gene editing technology and its key role in constructing biosynthetic pathways of cosmetic raw materials in S. cerevisiae. We also summarize the application of metabolic engineering strategies such as gene multi-copy integration, compartmentalization, transporter engineering, and multicellular system in the optimization of S. cerevisiae cell factories. Moreover, we present the latest progress in the biosynthesis of different types of cosmetic active ingredients in S. cerevisiae cell factories, such as terpenes, vitamins, polyphenols, as well as proteins and amino acids. While the potential and advantages of using S. cerevisiae for large-scale production of cosmetic raw materials are significant, a series of challenges remain, including incomplete biosynthetic pathway analysis, low biosynthesis yields, and difficult separation and purification. Looking ahead, the integration of artificial intelligence, machine learning, and other advanced technologies is expected to establish more efficient gene editing tools for the optimization of yeast cell factories and the biosynthesis of cosmetic raw materials, providing theoretical support and practical guidance for the sustainable development of the cosmetics industry.

Key words: Saccharomyces cerevisiae, cosmetic raw materials, synthetic biology, genome editing, metabolic engineering, yeast cell factories

摘要：

伴随消费者对化妆品的需求急剧增长，化妆品原料市场同步扩张。化妆品原料作为化妆品的核心成分，不仅承载着化妆品的主体功效和产品竞争力，同时对化妆品的安全也至关重要。合成生物学是以工程化设计为理念，利用基因编辑技术、计算机模拟技术和生物工程等技术对生物体进行有目标地设计、改造乃至重新合成的一门新兴交叉融合性学科。合成生物学的进步使微生物宿主能够以高效、具有成本竞争力和安全的方式合成有价值的天然产物。随着合成生物学的不断发展，酿酒酵母作为一种重要的微生物底盘细胞，在化妆品原料合成中的应用日益广泛。构建酿酒酵母细胞工厂异源生物合成化妆品原料作为一种有效的替代方案，具有环保、可持续的优点，可以减少对传统物理提取法的依赖以及规避化学合成法的污染问题。本文综述了酿酒酵母基因编辑技术的发展及其在化妆品原料生物合成途径构建中的关键作用，总结了基因多拷贝整合、区室化工程、转运工程、人工多细胞体系等代谢工程策略在化妆品原料酿酒酵母细胞工厂优化中的应用，并进一步从萜类、维生素类、多酚类、蛋白质与氨基酸类等不同类别的化妆品活性成分出发，阐述了酿酒酵母细胞工厂生物合成化妆品原料的最新进展。虽然酿酒酵母在化妆品原料大规模生产方面具有巨大潜能与优势，然而目前仍面临诸如产品生物合成途径未完全解析、生物合成水平较为低下、分离纯化困难等一系列挑战。未来，结合人工智能、机器学习等手段有望开发更为高效的基因编辑工具并应用于酿酒酵母细胞工厂的优化与化妆品原料成分的合成中，为化妆品行业的可持续发展提供理论支持和实践指导。

关键词: 酿酒酵母, 化妆品原料, 合成生物学, 基因组编辑, 代谢工程, 细胞工厂

CLC Number:

Q812

Yimeng Zuo, Jiaojiao Zhang, Jiazhang Lian. Enabling technology for the biosynthesis of cosmetic raw materials in Saccharomyces cerevisiae[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2024-070.

左一萌, 张姣姣, 连佳长. 酿酒酵母使能技术在化妆品原料合成中的应用[J]. 合成生物学, DOI: 10.12211/2096-8280.2024-070.

Figures/Tables 5

References 110

1	丁明珠, 李炳志, 王颖, 等. 合成生物学重要研究方向进展 [J]. 合成生物学, 2020, 1(1): 7-28.
	DING M Z, LI B Z, WANG Y, et al. Significant research progress in synthetic biology [J]. Synthetic Biology Journal, 2020, 1(1): 7-28.
2	LI Y, LIN Z, HUANG C, et al. Metabolic engineering of Escherichia coli using CRISPR-Cas9 meditated genome editing [J]. Metabolic Engineering, 2015, 31: 13-21.
3	LI T, LIU G S, ZHOU W, et al. Metabolic engineering of Saccharomyces cerevisiae to overproduce squalene [J]. Journal of Agricultural and Food Chemistry, 2020, 68(7): 2132-8.
4	JIANG Y K, XIA L, GAO S, et al. Engineering Saccharomyces cerevisiae for enhanced (-)-α-bisabolol production [J]. Synthetic and Systems Biotechnology, 2023, 8(2): 187-95.
5	ZHA W, AN T, LI T, et al. Reconstruction of the biosynthetic pathway of santalols under control of the GAL regulatory system in yeast [J]. ACS Synthetic Biology, 2020, 9(2): 449-56.
6	SHI S, WANG Z, SHEN L, et al. Synthetic biology: a new frontier in food production [J]. Trends in Biotechnology, 2022, 40(7): 781-803.
7	LI M, KILDEGAARD K R, CHEN Y, et al. De novo production of resveratrol from glucose or ethanol by engineered Saccharomyces cerevisiae [J]. Metabolic Engineering, 2015, 32: 1-11.
8	LIU T, LIU Y, LI L, et al. De novo biosynthesis of polydatin in Saccharomyces cerevisiae [J]. Journal of Agricultural and Food Chemistry, 2021, 69(21): 5917-25.
9	YANG S, CHEN R, CAO X, et al. De novo biosynthesis of the hops bioactive flavonoid xanthohumol in yeast [J]. Nature Communications, 2024, 15(1): 253.
10	SANTOS L O, SILVA P G P, LEMOS JUNIOR W J F, et al. Glutathione production by Saccharomyces cerevisiae: current state and perspectives [J]. Applied Microbiology and Biotechnology, 2022, 106(5-6): 1879-94.
11	OLIVEIRA A S, FERREIRA C, PEREIRA J O, et al. Spent brewer's yeast (Saccharomyces cerevisiae) as a potential source of bioactive peptides: An overview [J]. International Journal of Biological Macromolecules, 2022, 208: 1116-26.
12	KRISDAPHONG T, TOIDA T, POPP M, et al. Evaluation of immunological and moisturizing activities of β-glucan isolated from molasses yeast waste [J]. Indian Journal of Pharmaceutical Sciences, 2018, 80(5): 795-801.
13	江丽红, 董昌, 黄磊, 等. 酿酒酵母代谢工程技术 [J]. 生物工程学报, 2021, 37(5): 1578-602.
	JIANG L H, DONG C, HUANG L, et al. Metabolic engineering tools for Saccharomyces cerevisiae [J]. Chinese Journal of Biotechnology, 2021, 37(5): 1578-602.
14	HSU P D, LANDER E S, ZHANG F. Development and applications of CRISPR-Cas9 for genome engineering [J]. Cell, 2014, 157(6): 1262-78.
15	CONG L, RAN F A, COX D, et al. Multiplex genome engineering using CRISPR/Cas systems [J]. Science, 2013, 339(6121): 819-23.
16	JAKOČIŪNAS T, RAJKUMAR A S, ZHANG J, et al. CasEMBLR: Cas9-Facilitated multiloci genomic integration of in vivo assembled DNA parts in Saccharomyces cerevisiae [J]. ACS Synthetic Biology, 2015, 4(11): 1226-34.
17	ZHANG N, LI X, ZHOU Q, et al. Self-controlled in silico gene knockdown strategies to enhance the sustainable production of heterologous terpenoid by Saccharomyces cerevisiae [J]. Metabolic Engineering, 2024, 83: 172-82.
18	EAUCLAIRE S F, ZHANG J Z, RIVERA C G, et al. Combinatorial metabolic pathway assembly in the yeast genome with RNA-guided Cas9 [J]. Journal of Industrial Microbiology and Biotechnology, 2016, 43(7): 1001-15.
19	REIDER APEL A, D'ESPAUX L, WEHRS M, et al. A Cas9-based toolkit to program gene expression in Saccharomyces cerevisiae [J]. Nucleic Acids Research, 2017, 45(1): 496-508.
20	LIU T F, GOU Y W, ZHANG B, et al. Construction of ajmalicine and sanguinarine de novo biosynthetic pathways using stable integration sites in yeast [J]. Biotechnology and Bioengineering, 2022, 119(5): 1314-26.
21	LEE M E, DELOACHE W C, CERVANTES B, et al. A highly characterized yeast toolkit for modular, multipart assembly [J]. ACS Synthetic Biology, 2015, 4(9): 975-86.
22	ALPER H, FISCHER C, NEVOIGT E, et al. Tuning genetic control through promoter engineering [J]. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103(8): 3006.
23	LIU H, TIAN Y, ZHOU Y, et al. Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside [J]. Microbial Biotechnology, 2020, 14(6): 2605-16.
24	LIAN J, JIN R, ZHAO H. Construction of plasmids with tunable copy numbers in Saccharomyces cerevisiae and their applications in pathway optimization and multiplex genome integration [J]. Biotechnology and Bioengineering, 2016, 113(11): 2462-73.
25	LIAN J, MISHRA S, ZHAO H. Recent advances in metabolic engineering of Saccharomyces cerevisiae: new tools and their applications [J]. Metabolic Engineering, 2018, 50: 85-108.
26	BLEYKASTEN-GROSSHANS C, FRIEDRICH A, SCHACHERER J. Genome-wide analysis of intraspecific transposon diversity in yeast [J]. BMC Genomics, 2013, 14: 399.
27	PETES T D. Yeast ribosomal DNA genes are located on chromosome XII [J]. Proceedings of the National Academy of Sciences of the United States of America, 1979, 76(1): 410-4.
28	ZHENG H, WANG K, XU X, et al. Highly efficient rDNA-mediated multicopy integration based on the dynamic balance of rDNA in Saccharomyces cerevisiae [J]. Microbial Biotechnology, 2022, 15(5): 1511-24.
29	LIU L, LIU C, ZOU S, et al. Expression of cellulase genes in Saccharomyces cerevisiae via δ-integration subject to auxotrophic markers [J]. Biotechnology Letters, 2013, 35(8): 1303-7.
30	QI H, YU L, LI Y, et al. Developing multi-copy chromosomal integration strategies for heterologous biosynthesis of caffeic acid in Saccharomyces cerevisiae [J]. Frontiers in Microbiology, 2022, 13: 851706.
31	FANG C, WANG Q, SELVARAJ J N, et al. High copy and stable expression of the xylanase XynHB in Saccharomyces cerevisiae by rDNA-mediated integration [J]. Scientific Reports, 2017, 7(1): 8747.
32	RONDA C, MAURY J, JAKOČIUNAS T, et al. CrEdit: CRISPR mediated multi-loci gene integration in Saccharomyces cerevisiae [J]. Microbial Cell Factories, 2015, 14: 97.
33	PENG B, ESQUIROL L, LU Z, et al. An in vivo gene amplification system for high level expression in Saccharomyces cerevisiae [J]. Nature Communications, 2022, 13(1): 2895.
34	CUI H, NI X, SHAO W, et al. Functional manipulations of the tetramycin positive regulatory gene ttmRIV to enhance the production of tetramycin A and nystatin A1 in Streptomyces ahygroscopicus [J]. Journal of Industrial Microbiology and Biotechnology, 2015, 42(9): 1273-82.
35	SHI B, MA T, YE Z, et al. Systematic metabolic engineering of Saccharomyces cerevisiae for lycopene overproduction [J]. Journal of Agricultural and Food Chemistry, 2019, 67(40): 11148-57.
36	LIU G S, LI T, ZHOU W, et al. The yeast peroxisome: a dynamic storage depot and subcellular factory for squalene overproduction [J]. Metabolic Engineering, 2020, 57: 151-61.
37	ARENDT P, MIETTINEN K, POLLIER J, et al. An endoplasmic reticulum-engineered yeast platform for overproduction of triterpenoids [J]. Metabolic Engineering, 2017, 40: 165-75.
38	KIM J E, JANG I S, SON S H, et al. Tailoring the Saccharomyces cerevisiae endoplasmic reticulum for functional assembly of terpene synthesis pathway [J]. Metabolic Engineering, 2019, 56: 50-9.
39	PALAGE A M, WARD V C. Strategies for production of hydrophobic compounds [J]. Current Opinion in Biotechnology, 2022, 75: 102681.
40	THIAM A R, BELLER M. The why, when and how of lipid droplet diversity [J]. Journal of Cell Science, 2017, 130(2): 315-24.
41	SHI Y, WANG D, LI R, et al. Engineering yeast subcellular compartments for increased production of the lipophilic natural products ginsenosides [J]. Metabolic Engineering, 2021, 67: 104-11.
42	LIU X N, DING W T, JIANG H F. Engineering microbial cell factories for the production of plant natural products: from design principles to industrial-scale production [J]. Microbial Cell Factories, 2017, 16(1): 125.
43	BU X, LIN J Y, CHENG J, et al. Engineering endogenous ABC transporter with improving ATP supply and membrane flexibility enhances the secretion of β-carotene in Saccharomyces cerevisiae [J]. Biotechnology for Biofuels, 2020, 13: 168.
44	JIAO X, SHEN B, LI M, et al. Secretory production of tocotrienols in Saccharomyces cerevisiae [J]. ACS Synthetic Biology, 2022, 11(2): 788-99.
45	LI M, ZHOU P, CHEN M, et al. Spatiotemporal regulation of astaxanthin synthesis in S. cerevisiae [J]. ACS Synthetic Biology, 2022, 11(8): 2636-49.
46	AULAKH S K, SELLéS VIDAL L, SOUTH E J, et al. Spontaneously established syntrophic yeast communities improve bioproduction [J]. Nature Chemical Biology, 2023, 19(8): 951-61.
47	PENG H, DARLINGTON A P S, SOUTH E J, et al. A molecular toolkit of cross-feeding strains for engineering synthetic yeast communities [J]. Nature Microbiology, 2024, 9(3): 848-63.
48	CAMACHO-ZARAGOZA J M, HERNáNDEZ-CHáVEZ G, MORENO-AVITIA F, et al. Engineering of a microbial coculture of Escherichia coli strains for the biosynthesis of resveratrol. [J]. Microbial Cell Factories, 2016, 15(1): 163.
49	LIU X, LI X B, JIANG J, et al. Convergent engineering of syntrophic Escherichia coli coculture for efficient production of glycosides [J]. Metabolic Engineering, 2018, 47: 243-53.
50	ZHOU X, ZHANG 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): 22386-97.
51	HE N, LI D-F, YU H-W, et al. Construction of an artificial microbial consortium for green production of (-)-ambroxide [J]. ACS Sustainable Chemistry & Engineering, 2023, 11(5): 1939-48.
52	LV X, ZHOU X, MA J, et al. Engineered Saccharomyces cerevisiae for the de novo biosynthesis of (-)-menthol [J]. Journal of Fungi, 2022, 8(9): 982.
53	KONG X, WU Y, YU W, et al. Efficient synthesis of limonene in Saccharomyces cerevisiae using combinatorial metabolic engineering strategies [J]. Journal of Agricultural and Food Chemistry, 2023, 71(20): 7752-64.
54	PENG B, BANDARI N C, LU Z, et al. Engineering eukaryote-like regulatory circuits to expand artificial control mechanisms for metabolic engineering in Saccharomyces cerevisiae [J]. Communications Biology, 2022, 5(1): 135.
55	RASOOL A, ZHANG G, LI Z, et al. Engineering of the terpenoid pathway in Saccharomyces cerevisiae co-overproduces squalene and the non-terpenoid compound oleic acid [J]. Chemical Engineering Science, 2016, 152: 457-67.
56	ZHOU C, LI M, LU S, et al. Engineering of cis-element in Saccharomyces cerevisiae for efficient accumulation of value-added compound squalene via downregulation of the downstream metabolic flux [J]. Journal of Agricultural and Food Chemistry, 2021, 69(42): 12474-84.
57	ZHU Z T, DU M M, GAO B, et al. Metabolic compartmentalization in yeast mitochondria: burden and solution for squalene overproduction [J]. Metabolic Engineering, 2021, 68: 232-45.
58	CHENG X, PANG Y, BAN Y, et al. Application of multiple strategies to enhance oleanolic acid biosynthesis by engineered Saccharomyces cerevisiae [J]. Bioresource Technology, 2024, 401: 130716.
59	HUANG L, LI J, YE H, et al. Molecular characterization of the pentacyclic triterpenoid biosynthetic pathway in Catharanthus roseus [J]. Planta, 2012, 236(5): 1571-81.
60	LU C, ZHANG C, ZHAO F, et al. Biosynthesis of ursolic acid and oleanolic acid in Saccharomyces cerevisiae [J]. AIChE Journal, 2018, 64(11): 3794-802.
61	JIN K, SHI X, LIU J, et al. Combinatorial metabolic engineering enables the efficient production of ursolic acid and oleanolic acid in Saccharomyces cerevisiae [J]. Bioresource Technology, 2023, 374: 128819.
62	JIA N, LI J, ZANG G, et al. Engineering Saccharomyces cerevisiae for high-efficient production of ursolic acid via cofactor engineering and acetyl-CoA optimization [J]. Biochemical Engineering Journal, 2024, 203: 109189.
63	SHEN X, GUO M, YU H, et al. Propionibacterium acnes related anti-inflammation and skin hydration activities of madecassoside, a pentacyclic triterpene saponin from Centella asiatica [J]. Bioscience Biotechnology and Biochemistry, 2019, 83(3): 561-8.
64	ZHAO X, WEI W, LI S, et al. Elucidation of the biosynthesis of asiaticosideand its reconstitution in yeast [J]. ACS Sustainable Chemistry & Engineering, 2024, 12(10): 4028-40.
65	LI M, MA M, WU Z, et al. Advances in the biosynthesis and metabolic engineering of rare ginsenosides [J]. Applied Microbiology and Biotechnology, 2023, 107(11): 3391-404.
66	REN S, SUN Q, ZHANG L, et al. Sustainable production of rare oleanane-type ginsenoside Ro with an artificial glycosylation pathway in Saccharomyces cerevisiae [J]. Green Chemistry, 2022, 24(21): 8302-13.
67	ZHAO Y, ZHANG Y, NIELSEN J, et al. Production of β-carotene in Saccharomyces cerevisiae through altering yeast lipid metabolism [J]. Biotechnology and Bioengineering, 2021, 118(5): 2043-52.
68	BU X, LIN J Y, DUAN C Q, et al. Dual regulation of lipid droplet-triacylglycerol metabolism and ERG9 expression for improved β-carotene production in Saccharomyces cerevisiae [J]. Microbial Cell Factories, 2022, 21(1): 3.
69	FATHI Z, TRAMONTIN L R R, EBRAHIMIPOUR G, et al. Metabolic engineering of Saccharomyces cerevisiae for production of β-carotene from hydrophobic substrates [J]. FEMS Yeast Research, 2021, 21(1).
70	CHEN Y, XIAO W, WANG Y, et al. Lycopene overproduction in Saccharomyces cerevisiae through combining pathway engineering with host engineering [J]. Microbial Cell Factories, 2016, 15(1): 113.
71	HUANG G, LI J, LIN J, et al. Multi-modular metabolic engineering and efflux engineering for enhanced lycopene production in recombinant Saccharomyces cerevisiae [J]. Journal of Industrial Microbiology and Biotechnology, 2024, 51.
72	XIE W, LV X, YE L, et al. Construction of lycopene-overproducing Saccharomyces cerevisiae by combining directed evolution and metabolic engineering [J]. Metabolic Engineering, 2015, 30: 69-78.
73	ZHOU K, YU C, LIANG N, et al. Adaptive evolution and metabolic engineering boost lycopene production in Saccharomyces cerevisiae via enhanced precursors supply and utilization [J]. Journal of Agricultural and Food Chemistry, 2023, 71(8): 3821-31.
74	MA J, YAN H H, QIN C Q, et al. Accumulation of astaxanthin by co-fermentation of spirulina platensis and recombinant Saccharomyces cerevisiae [J]. Applied Biochemistry and Biotechnology, 2022, 194(2): 988-99.
75	SJ S, VEERABHADRAPPA B, SUBRAMANIYAN S, et al. Astaxanthin enhances the longevity of Saccharomyces cerevisiae by decreasing oxidative stress and apoptosis [J]. FEMS Yeast Research, 2019, 19(1).
76	ZHOU D, FEI Z, LIU G, et al. The bioproduction of astaxanthin: a comprehensive review on the microbial synthesis and downstream extraction [J]. Biotechnology Advances, 2024, 74: 108392.
77	ZHOU P, XIE W, LI A, et al. Alleviation of metabolic bottleneck by combinatorial engineering enhanced astaxanthin synthesis in Saccharomyces cerevisiae [J]. Enzyme And Microbial Technology, 2017, 100: 28-36.
78	ZHOU P, YE L, XIE W, et al. Highly efficient biosynthesis of astaxanthin in Saccharomyces cerevisiae by integration and tuning of algal crtZ and bkt [J]. Applied Microbiology and Biotechnology, 2015, 99(20): 8419-28.
79	HU Q, ZHANG T, YU H, et al. Selective biosynthesis of retinol in S. cerevisiae [J]. Bioresources and Bioprocessing, 2022, 9(1): 22.
80	SUN L, KWAK S, JIN Y S. Vitamin A production by engineered Saccharomyces cerevisiae from xylose via two-phase in situ extraction [J]. ACS Synthetic Biology, 2019, 8(9): 2131-40.
81	GUO J, SUN X, YUAN Y, et al. Metabolic engineering of Saccharomyces cerevisiae for vitamin B5 production [J]. Journal of Agricultural and Food Chemistry, 2023, 71(19): 7408-17.
82	MADAAN P, SIKKA P, MALIK D S. Cosmeceutical aptitudes of niacinamide: a Review [J]. Recent Advances in Anti-Infective Drug Discovery, 2021, 16(3): 196-208.
83	CHENG F, LI K X, WU S S, et al. Biosynthesis of nicotinamide mononucleotide: synthesis method, enzyme, and biocatalytic system [J]. Journal of Agricultural and Food Chemistry, 2024, 72(7): 3302-13.
84	HE Z, YANG X, TIAN X, et al. Yeast cell surface engineering of a nicotinamide riboside kinase for the production of β-nicotinamide mononucleotide via whole-cell catalysis [J]. ACS Synthetic Biology, 2022, 11(10): 3451-9.
85	PENG H, CHEN R, SHAW W M, et al. Modular metabolic engineering and synthetic coculture strategies for the production of aromatic compounds in yeast [J]. ACS Synthetic Biology, 2023, 12(6): 1739-49.
86	SHEN B, ZHOU P, JIAO X, et al. Fermentative production of Vitamin E tocotrienols in Saccharomyces cerevisiae under cold-shock-triggered temperature control [J]. Nature Communications, 2020, 11(1): 5155.
87	MENG L J, DIAO M X, WANG Q Y, et al. Efficient biosynthesis of resveratrol via combining phenylalanine and tyrosine pathways in Saccharomyces cerevisiae [J]. Microbial Cell Factories, 2023, 22(1).
88	EICHENBERGER M, SCHWANDER T, HüPPI S, et al. The catalytic role of glutathione transferases in heterologous anthocyanin biosynthesis [J]. Nature Catalysis, 2023, 6(10): 927-38.
89	ZHOU P, YUE C, SHEN B, et al. Metabolic engineering of Saccharomyces cerevisiae for enhanced production of caffeic acid [J]. Applied Microbiology and Biotechnology, 2021, 105(14-15): 5809-19.
90	CHEN R, GAO J, YU W, et al. Engineering cofactor supply and recycling to drive phenolic acid biosynthesis in yeast [J]. Nature Chemical Biology, 2022, 18(5): 520-9.
91	LIU L, LIU H, ZHANG W, et al. Engineering the biosynthesis of caffeic acid in Saccharomyces cerevisiae with heterologous enzyme combinations [J]. Engineering, 2019, 5(2): 287-95.
92	LI Y, MAO J, LIU Q, et al. De novo biosynthesis of caffeic acid from glucose by engineered Saccharomyces cerevisiae [J]. ACS Synthetic Biology, 2020, 9(4): 756-65.
93	XU W, LIU M, LI H, et al. De novo synthesis of chrysin in Saccharomyces cerevisiae [J]. Journal of Agricultural and Food Chemistry, 2024, 72(12): 6481-90.
94	TIPPELT A, NETT M. Saccharomyces cerevisiae as host for the recombinant production of polyketides and nonribosomal peptides [J]. Microbial Cell Factories, 2021, 20(1): 161.
95	PINMANEE P, SOMPINIT K, JANTIMAPORN A, et al. Purification and immobilization of superoxide dismutase obtained from Saccharomyces cerevisiae TBRC657 on bacterial cellulose and its protective effect against oxidative damage in fibroblasts [J]. Biomolecules, 2023, 13(7).
96	KOBAYASHI J, SASAKI D, HARA K Y, et al. Metabolic engineering of the L-serine biosynthetic pathway improves glutathione production in Saccharomyces cerevisiae [J]. Microbial Cell Factories, 2022, 21(1): 153.
97	KOBAYASHI J, SASAKI D, KONDO A. A procedure for precise determination of glutathione produced by Saccharomyces cerevisiae [J]. Bio-protocol Journal, 2018, 8(12): e2887.
98	HU X, SHEN X, ZHU S, et al. Optimization of glutathione production in Saccharomyces cerevisiae HBSD-W08 using plackett-burman and central composite rotatable designs [J]. BMC Microbiology, 2023, 23(1): 11.
99	CHEN H, CAO X, ZHU N, et al. A stepwise control strategy for glutathione synthesis in Saccharomyces cerevisiae based on oxidative stress and energy metabolism [J]. World Journal of Microbiology and Biotechnology, 2020, 36(8): 117.
100	GELSE K, PöSCHL E, AIGNER T. Collagens-structure, function, and biosynthesis [J]. Advanced Drug Delivery Reviews, 2003, 55(12): 1531-46.
101	VAUGHN P R, GALANIS M, RICHARDS K M, et al. Production of recombinant hydroxylated human type III collagen fragment in Saccharomyces cerevisiae [J]. DNA and Cell Biology 1998, 17(6): 511-8.
102	HENGARDI M T, LIANG C, MADIVANNAN K, et al. Reversing the directionality of reactions between non-oxidative pentose phosphate pathway and glycolytic pathway boosts mycosporine-like amino acid production in Saccharomyces cerevisiae [J]. Microbial Cell Factories, 2024, 23(1): 121.
103	KIM S, PARK B G, JIN H, et al. Efficient production of natural sunscreens shinorine, porphyra-334, and mycosporine-2-glycine in Saccharomyces cerevisiae [J]. Metabolic Engineering, 2023, 78: 137-47.
104	VAN DER HOEK S A, RUSNáK M, WANG G, et al. Engineering precursor supply for the high-level production of ergothioneine in Saccharomyces cerevisiae [J]. Metabolic Engineering, 2022, 70: 129-42.
105	DIVATE N R, CHEN G H, DIVATE R D, et al. Metabolic engineering of Saccharomyces cerevisiae for improvement in stresses tolerance [J]. Bioengineered, 2017, 8(5): 524-35.
106	刘少奇. 酿酒酵母中水杨酸生物合成研究 [D], 2017.
	LIU S Q. Study on the biosynthesis of salicylic acid in Saccharomyces cerevisiae [D], 2017.
107	TANG H, LIN S, DENG J, et al. Engineering yeast for the de novo synthesis of jasmonates [J]. Nature Synthesis, 2024, 3(2): 224-35.
108	LOHMANN K J. A candidate magnetoreceptor [J]. Nature Materials, 2016, 15(2): 136-8.
109	IGNEA C, RAADAM M H, KOUTSAVITI A, et al. Expanding the terpene biosynthetic code with non-canonical 16 carbon atom building blocks [J]. Nature Communications, 2022, 13(1): 5188.
110	曾涛, 巫瑞波. 数据驱动的酶反应预测与设计 [J]. 合成生物学, 2023, 4(3): 535-50.
	ZENG T, WU R B. Data-driven prediction and design for enzymatic reactions [J]. Synthetic Biology Journal, 2023, 4(3): 535-550.

物质类别	物质名称	英文名	分子式	功能	发酵方式	产量	改造策略	参考文献
萜类	α-红没药醇	α-Bisabolol	C₁₅H₂₆O	抗菌、抗炎、抗过敏	5 L发酵罐	7.02 g/L	引入MrBBS，替换内源ERG9启动子，融合表达ERG20和MrBBS，强化MVA途径，过表达内源转运蛋白PDR15	[4]
	α-檀香醇	α-Santalol	C₁₅H₂₄O	加速伤口愈合、促进皮肤再生、减少红血丝、抗敏	5 L发酵罐	1.18 g/L	使用GAL启动子表达SaSSy、CYP736A167和SaCPR2，使用HXT1启动子替换酵母自身ERG9启动子，过表达tHMG1和UPC2-1	[5]
	薄荷醇	Menthol	C₁₀H₂₀O	清凉、舒缓止痒、增强皮肤渗透性	摇瓶	6.28 mg/L	强化MVA途径，动态调节ERG20基因	[52]
	柠檬烯	Limonene	C₁₀H₁₆	增香、抗氧化、镇定消炎作用	3 L 发酵罐	2.63 g/L	引入柠檬烯合酶的截断突变体tLimS并优化其拷贝数，引入 ERG20 抑制蛋白，强化MVA途径，优化 NADPH 供应并结合线粒体区室化策略	[53]
	橙花叔醇	Nerolidol	C₁₅H₂₆O	抗炎、抗氧化、神经保护作用	摇瓶	2.54 g/L	基于四环素抑制和37 °C诱导的GAL调控系统，用HAC1启动子控制人工转录因子表达	[54]
	角鲨烯	Squalene	C₁₅H₃₀	亲肤性、渗透性，化妆品中保湿及抗氧化作用	5 L 发酵罐	9.47 g/L	过表达SpNADH-HMGR、ADH2、DzADA，增强乙醇耐受性	[3]
	角鲨烯	Squalene	C₁₅H₃₀	亲肤性、渗透性，化妆品中保湿及抗氧化作用	5 L 发酵罐	21.10 g/L	过表达tHMG1、ERG20、ERG9，结合线粒体区室化工程	[57]
	齐墩果酸	Oleanolic acid	C₃₀H₄₈O₃	改善真皮胶原蛋白，增加皮肤弹性，化妆品中抗炎、抗衰剂	5 L 发酵罐	1.23 g/L	整合GgbAS、MtCYP716A12和MtCPR基因，建立GEM模型，结合FBA和OptKnock计算优化代谢途径	[17]
	齐墩果酸	Oleanolic acid	C₃₀H₄₈O₃	改善真皮胶原蛋白，增加皮肤弹性，化妆品中抗炎、抗衰剂	100 L 发酵罐	4.07 g/L	引入植物源细胞色素b5，使用糖诱导启动子P _ADH2 表达rSE	[58]
	熊果酸	Ursolic acid	C₃₀H₄₈O₃	镇静、抗炎、抗菌、抗氧化性，化妆品中抗衰成分	5 L 发酵罐	2.33 g/L	组合优化ALD6和MPC2以及rHMGR、ADA 和 GAPC 平衡乙酰辅酶A与NADH/NADPH供应	[62]
	积雪草苷	Asiaticoside	C₄₈H₇₈O₁₉	润肤剂，改善皮肤红肿、炎症及伤口愈合	5 L 发酵罐	772.30 μg/L	鉴定5种积雪草苷合成的C28糖基转移酶结合途径工程实现从头合成	[64]
	人参皂苷Ro	Ginsenoside Ro	C₄₈H₇₆O₁₉	提高角质层的含水量，化妆品中美白抗皱成分	5 L 发酵罐	0.53 g/L	挖掘类纤维素合酶Pn022859，引入AtUGDH，筛选到2个糖基转移酶UGT73F3及UGT73P40，实现从头合成	[66]
	β-胡萝卜素	β-Carotene	C₄₀H₅₆	天然抗氧化剂、清除自由基、抗炎	摇瓶	477.90 mg/L	引入来自含油酵母脂肪酶LIP2，LIP7和LIP8，添加1%橄榄油	[69]
	番茄红素	Lycopene	C₄₀H₅₆	抗氧化、抗炎	7 L 发酵罐	8.15 g/L	利用ARTP诱变结合H₂O₂诱导的适应性进化策略增强FPP供应，过表达CrtE，引入工程化的CrtI突变体（Y160F&N576S）	[73]
	虾青素	Astaxanthin	C₄₀H₅₂O₄	抗氧化	5 L 发酵罐	446.40 mg/L	鉴定OPI3和HRD1作为新的工程目标，通过平衡β-胡萝卜素羟化酶和转酮酶、脂滴工程以及温度响应动态调控	[45]
维生素类	生育酚（维生素E，V_E）	Tocopherol	C₂₉H₅O₂	抗衰老	5 L 发酵罐	320.00 mg/L	GAL10和GAL1启动子驱动tHMG1、CrtE、HPPD、tMPBQMT、SyHPT、tTMT和tTC等基因表达，增加SyHPT、tTMT和tTC拷贝数，引入温控系统GAL4M9	[86]
	视黄醇视黄醛（V_A）	Retinol Retinal	C₂₀H₃₀O C₂₀H₂₈O	增强表皮增殖和增加胶原蛋白的产生	3 L 发酵罐	视黄醇 1.26 g/L 视黄醛 2.10 g/L	引入β-胡萝卜素合成途径和β-胡萝卜素15,15'-二氧合酶（BCMO）编码基因，采用两阶段发酵，维生素A滴度为3.35 g/L	[80]
	维生素C（Vc，抗坏血酸）	Ascorbic acid	C₆H₈O₆	预防皮肤色素沉着、刺激胶原蛋白形成	摇瓶	44.00 mg/L	引入外源基因GME、VTC2、VTC4、GalDH和GLDH，融合表达L-GalDH和L-GLDH，增加VTC2拷贝，外源添加L-半乳糖或GSHVc	[85]
	D-泛酸（V_B5）	D-pantothenic acid	C₉H₁₇NO₄₅	具有舒缓、修护作用	1 L 发酵罐	4.00 g/L	构建异源β-丙氨酸异源合成途径，组合筛选泛酸合成关键酶（AHAS/KARI/DHAD/ KPHMT/KPR），添加β-丙氨酸	[81]
	烟酰胺核糖核苷	NMN	C₁₁H₁₅N₂O₈PP	抗衰老、抚平皱纹	30 mL 反应液	12.60 g/L	构建NRK-2表面展示菌株，以NR为底物全细胞催化合成β- NMN	[84]
多酚类	白藜芦醇	Resveratrol	C₁₄H₁₂O₃	防止光老化、清除自由基，化妆品中抗氧剂、抗菌剂和美白剂	3 L 发酵罐	4.10 g/L	引入RtPAL/TAL，联合苯丙氨酸与酪氨酸途径重建白藜芦醇合成途径，过表达Pc4CL 、VvSTS，敲除 DPP1	[87]
	花青素	Anthocyanin	C₁₅H₁₁ClO₆	抗炎、抗衰老、美容，化妆品抗衰剂、抗敏剂	——	~150 μM	引入DFR、AtLDOX，证实ArGSTs的催化作用，实现从头合成	[88]
	咖啡酸	Caffeic acid	C₉H₈O₄	抗氧化、抗菌、抗炎	5 L 发酵罐	5.5 g/L	在咖啡酸生产菌株的基础上，增加前体供应，计酿酒酵母三种辅因子	[90]
	黄腐酚	Xanthohumol	C₂₁H₂₂O₅	抗菌、抗炎、抗氧化，用于美白防晒类化妆品	摇瓶	0.14 mg/L	过表达HlPT1L、HlOMT3sc，融合表达 IDI1-HlPT1L_Δ1-86，结合过氧化物酶体工程	[9]
	白杨素	Chrysin	C₁₅H₁₀O₄	抗炎、抗氧化，用于美白、防晒、抗衰抗皱类化妆品	摇瓶	41.90 mg/L	引入ZmPAL，融合表达 PcFNSI–ScCPR–EbFNSI-1，过表达CIT、MAC1/3、CTP1、YHM2、RtME和MDH	[93]
	红景天苷	Salidroside	C₁₄H₂₀O₇	抗氧化、消炎，用于抗皱美白类化妆品	5 L 发酵罐	26.55 g/L	引入ARO4^K229L和ARO^7G141S，过表达RKI1和TKL1，敲除PHA2和PDC1	[23]
蛋白、多肽及氨基酸类	超氧化歧化酶	Superoxide dismutase	——	抗氧化	摇瓶	513.74 U/mg	/	[95]
	谷胱甘肽	Glutathione	C₁₀H₁₇N₃O₆S	抗氧化	摇瓶	64.00 mg/L	过表达SER3、SHM2和CYS4	[96]
	霉孢素类氨基酸	MAAs	——	防晒，消炎	5 L 发酵罐	Shinorine 1.53 g/L 卟啉-334 1.21 g/L	整合木糖途径，引入三个编码DDGS基因和ATP抓取酶表达盒，敲除HXK2和TAL1，引入4个D-Ala-D-Ala连接酶，成功生产了三种双取代的MAAs	[103]
其它类	海藻糖	Trehalose	C₁₂H₂₂O₁₁	作为化妆品中的保湿、抗辐射成分	摇瓶	~140 mg/g	过表达ARI1基因	[105]
其它类	水杨酸	Salicylic acid	C₇H₆O₃	去除角质、控制青春痘、淡化色素斑、缩小毛孔等作用	摇瓶	46.71 mg/L	引入外源水杨酸合成基因entC和PfpchB，优化启动子、改造加强莽草酸途径并解除关键酶ARO4的反馈抑制、加强磷酸戊糖途径	[90]

物质类别	物质名称	英文名	分子式	功能	发酵方式	产量	改造策略	参考文献
萜类	α-红没药醇	α-Bisabolol	C₁₅H₂₆O	抗菌、抗炎、抗过敏	5 L发酵罐	7.02 g/L	引入MrBBS，替换内源ERG9启动子，融合表达ERG20和MrBBS，强化MVA途径，过表达内源转运蛋白PDR15	[4]
	α-檀香醇	α-Santalol	C₁₅H₂₄O	加速伤口愈合、促进皮肤再生、减少红血丝、抗敏	5 L发酵罐	1.18 g/L	使用GAL启动子表达SaSSy、CYP736A167和SaCPR2，使用HXT1启动子替换酵母自身ERG9启动子，过表达tHMG1和UPC2-1	[5]
	薄荷醇	Menthol	C₁₀H₂₀O	清凉、舒缓止痒、增强皮肤渗透性	摇瓶	6.28 mg/L	强化MVA途径，动态调节ERG20基因	[52]
	柠檬烯	Limonene	C₁₀H₁₆	增香、抗氧化、镇定消炎作用	3 L 发酵罐	2.63 g/L	引入柠檬烯合酶的截断突变体tLimS并优化其拷贝数，引入 ERG20 抑制蛋白，强化MVA途径，优化 NADPH 供应并结合线粒体区室化策略	[53]
	橙花叔醇	Nerolidol	C₁₅H₂₆O	抗炎、抗氧化、神经保护作用	摇瓶	2.54 g/L	基于四环素抑制和37 °C诱导的GAL调控系统，用HAC1启动子控制人工转录因子表达	[54]
	角鲨烯	Squalene	C₁₅H₃₀	亲肤性、渗透性，化妆品中保湿及抗氧化作用	5 L 发酵罐	9.47 g/L	过表达SpNADH-HMGR、ADH2、DzADA，增强乙醇耐受性	[3]
	角鲨烯	Squalene	C₁₅H₃₀	亲肤性、渗透性，化妆品中保湿及抗氧化作用	5 L 发酵罐	21.10 g/L	过表达tHMG1、ERG20、ERG9，结合线粒体区室化工程	[57]
	齐墩果酸	Oleanolic acid	C₃₀H₄₈O₃	改善真皮胶原蛋白，增加皮肤弹性，化妆品中抗炎、抗衰剂	5 L 发酵罐	1.23 g/L	整合GgbAS、MtCYP716A12和MtCPR基因，建立GEM模型，结合FBA和OptKnock计算优化代谢途径	[17]
	齐墩果酸	Oleanolic acid	C₃₀H₄₈O₃	改善真皮胶原蛋白，增加皮肤弹性，化妆品中抗炎、抗衰剂	100 L 发酵罐	4.07 g/L	引入植物源细胞色素b5，使用糖诱导启动子P _ADH2 表达rSE	[58]
	熊果酸	Ursolic acid	C₃₀H₄₈O₃	镇静、抗炎、抗菌、抗氧化性，化妆品中抗衰成分	5 L 发酵罐	2.33 g/L	组合优化ALD6和MPC2以及rHMGR、ADA 和 GAPC 平衡乙酰辅酶A与NADH/NADPH供应	[62]
	积雪草苷	Asiaticoside	C₄₈H₇₈O₁₉	润肤剂，改善皮肤红肿、炎症及伤口愈合	5 L 发酵罐	772.30 μg/L	鉴定5种积雪草苷合成的C28糖基转移酶结合途径工程实现从头合成	[64]
	人参皂苷Ro	Ginsenoside Ro	C₄₈H₇₆O₁₉	提高角质层的含水量，化妆品中美白抗皱成分	5 L 发酵罐	0.53 g/L	挖掘类纤维素合酶Pn022859，引入AtUGDH，筛选到2个糖基转移酶UGT73F3及UGT73P40，实现从头合成	[66]
	β-胡萝卜素	β-Carotene	C₄₀H₅₆	天然抗氧化剂、清除自由基、抗炎	摇瓶	477.90 mg/L	引入来自含油酵母脂肪酶LIP2，LIP7和LIP8，添加1%橄榄油	[69]
	番茄红素	Lycopene	C₄₀H₅₆	抗氧化、抗炎	7 L 发酵罐	8.15 g/L	利用ARTP诱变结合H₂O₂诱导的适应性进化策略增强FPP供应，过表达CrtE，引入工程化的CrtI突变体（Y160F&N576S）	[73]
	虾青素	Astaxanthin	C₄₀H₅₂O₄	抗氧化	5 L 发酵罐	446.40 mg/L	鉴定OPI3和HRD1作为新的工程目标，通过平衡β-胡萝卜素羟化酶和转酮酶、脂滴工程以及温度响应动态调控	[45]
维生素类	生育酚（维生素E，V_E）	Tocopherol	C₂₉H₅O₂	抗衰老	5 L 发酵罐	320.00 mg/L	GAL10和GAL1启动子驱动tHMG1、CrtE、HPPD、tMPBQMT、SyHPT、tTMT和tTC等基因表达，增加SyHPT、tTMT和tTC拷贝数，引入温控系统GAL4M9	[86]
	视黄醇视黄醛（V_A）	Retinol Retinal	C₂₀H₃₀O C₂₀H₂₈O	增强表皮增殖和增加胶原蛋白的产生	3 L 发酵罐	视黄醇 1.26 g/L 视黄醛 2.10 g/L	引入β-胡萝卜素合成途径和β-胡萝卜素15,15'-二氧合酶（BCMO）编码基因，采用两阶段发酵，维生素A滴度为3.35 g/L	[80]
	维生素C（Vc，抗坏血酸）	Ascorbic acid	C₆H₈O₆	预防皮肤色素沉着、刺激胶原蛋白形成	摇瓶	44.00 mg/L	引入外源基因GME、VTC2、VTC4、GalDH和GLDH，融合表达L-GalDH和L-GLDH，增加VTC2拷贝，外源添加L-半乳糖或GSHVc	[85]
	D-泛酸（V_B5）	D-pantothenic acid	C₉H₁₇NO₄₅	具有舒缓、修护作用	1 L 发酵罐	4.00 g/L	构建异源β-丙氨酸异源合成途径，组合筛选泛酸合成关键酶（AHAS/KARI/DHAD/ KPHMT/KPR），添加β-丙氨酸	[81]
	烟酰胺核糖核苷	NMN	C₁₁H₁₅N₂O₈PP	抗衰老、抚平皱纹	30 mL 反应液	12.60 g/L	构建NRK-2表面展示菌株，以NR为底物全细胞催化合成β- NMN	[84]
多酚类	白藜芦醇	Resveratrol	C₁₄H₁₂O₃	防止光老化、清除自由基，化妆品中抗氧剂、抗菌剂和美白剂	3 L 发酵罐	4.10 g/L	引入RtPAL/TAL，联合苯丙氨酸与酪氨酸途径重建白藜芦醇合成途径，过表达Pc4CL 、VvSTS，敲除 DPP1	[87]
	花青素	Anthocyanin	C₁₅H₁₁ClO₆	抗炎、抗衰老、美容，化妆品抗衰剂、抗敏剂	——	~150 μM	引入DFR、AtLDOX，证实ArGSTs的催化作用，实现从头合成	[88]
	咖啡酸	Caffeic acid	C₉H₈O₄	抗氧化、抗菌、抗炎	5 L 发酵罐	5.5 g/L	在咖啡酸生产菌株的基础上，增加前体供应，计酿酒酵母三种辅因子	[90]
	黄腐酚	Xanthohumol	C₂₁H₂₂O₅	抗菌、抗炎、抗氧化，用于美白防晒类化妆品	摇瓶	0.14 mg/L	过表达HlPT1L、HlOMT3sc，融合表达 IDI1-HlPT1L_Δ1-86，结合过氧化物酶体工程	[9]
	白杨素	Chrysin	C₁₅H₁₀O₄	抗炎、抗氧化，用于美白、防晒、抗衰抗皱类化妆品	摇瓶	41.90 mg/L	引入ZmPAL，融合表达 PcFNSI–ScCPR–EbFNSI-1，过表达CIT、MAC1/3、CTP1、YHM2、RtME和MDH	[93]
	红景天苷	Salidroside	C₁₄H₂₀O₇	抗氧化、消炎，用于抗皱美白类化妆品	5 L 发酵罐	26.55 g/L	引入ARO4^K229L和ARO^7G141S，过表达RKI1和TKL1，敲除PHA2和PDC1	[23]
蛋白、多肽及氨基酸类	超氧化歧化酶	Superoxide dismutase	——	抗氧化	摇瓶	513.74 U/mg	/	[95]
	谷胱甘肽	Glutathione	C₁₀H₁₇N₃O₆S	抗氧化	摇瓶	64.00 mg/L	过表达SER3、SHM2和CYS4	[96]
	霉孢素类氨基酸	MAAs	——	防晒，消炎	5 L 发酵罐	Shinorine 1.53 g/L 卟啉-334 1.21 g/L	整合木糖途径，引入三个编码DDGS基因和ATP抓取酶表达盒，敲除HXK2和TAL1，引入4个D-Ala-D-Ala连接酶，成功生产了三种双取代的MAAs	[103]
其它类	海藻糖	Trehalose	C₁₂H₂₂O₁₁	作为化妆品中的保湿、抗辐射成分	摇瓶	~140 mg/g	过表达ARI1基因	[105]
其它类	水杨酸	Salicylic acid	C₇H₆O₃	去除角质、控制青春痘、淡化色素斑、缩小毛孔等作用	摇瓶	46.71 mg/L	引入外源水杨酸合成基因entC和PfpchB，优化启动子、改造加强莽草酸途径并解除关键酶ARO4的反馈抑制、加强磷酸戊糖途径	[90]

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