红酵母基因组和代谢工程改造研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2022-1426

摘要/Abstract

摘要：

红酵母是一类产红色素酵母的总称，广泛分布于土壤、海洋、江河、湖泊等各种生态环境。很多红酵母菌株具有生产多糖、油脂、类胡萝卜素等活性物质的能力，在养殖、食品、医药和化妆品等领域具有很大的应用潜力。近年来对红酵母的研究逐渐深入，对不同红酵母的基因组序列和代谢关键酶进行了研究，扩展了对这类重要酵母的深入认识。此外，对红酵母的基因组编辑和代谢工程改造也取得了进展，为提高其工业应用效率奠定了基础。本文综述了红酵母的生物技术应用，以及红酵母基因组分析和代谢工程改造相关的研究进展，为未来更深入理解红酵母的生理代谢和利用红酵母转化可再生生物质资源，进行可持续生产提供基础。

关键词: 红酵母, 活性物质, 基因组, 代谢工程改造, 生物技术应用

Abstract:

Red yeast is a general term for a class of red pigment-producing yeast, and they are widely distributed in various ecological environments such as soil, sea, rivers and lakes. Red yeasts have the ability to produce polysaccharides, oils, carotenoids and other active substances and thus own great potential for applications in agriculture, food, medicine and cosmetics. In recent years, studies on red yeast including their applications, genome sequencing and key metabolic enzymes have expanded the in-depth knowledge of this important group of yeast. In addition, progress has been made in genome editing and metabolic engineering modification of these yeasts, providing basis for developing more efficient red yeast strains for industrial applications. Here, we review the applications of red yeast and related research advances in genomic studies and metabolic engineering. This review would be helpful for better understanding the physiology and metabolic features of red yeast, as well as utilization of renewable biomass for sustainable bioproduction using red yeast.

Key words: red yeast, bioactive substances, genome, metabolic engineering, biotechnology applications

李雨真, 梅天秀, 李治文, 王淇, 李俊, 邹岳, 赵心清. 红酵母基因组和代谢工程改造研究进展[J]. 生物技术通报, 2023, 39(7): 67-79.

LI Yu-zhen, MEI Tian-xiu, LI Zhi-wen, WANG Qi, LI Jun, ZOU Yue, ZHAO Xin-qing. Advances in Genomic Studies and Metabolic Engineering of Red Yeasts[J]. Biotechnology Bulletin, 2023, 39(7): 67-79.

图/表 5

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红酵母种Red yeast species	活性成分及用途Active ingredients and uses	参考文献Reference
黏红酵母 R. glutinis	红色素、类胡萝卜素、多糖、辅酶Q₁₀、橄榄的软化、处理工业污水	[17,35⇓ -37]
胶红酵母 R. mucilaginosa	氨基酸、酶、番茄红素、β-胡萝卜素、虾青素、多种脂肪酸、多糖、化妆品成分、饲料添加剂	[15,19,23⇓ -25,38 -39]
圆红酵母 R. toruloides	类胡萝卜素、虾青素、油脂、倍半萜、脂肪酸酯、脂肪醇、化妆品成分	[28,40⇓ -42]
克氏红酵母 R. kratochvilovae	脂类、外糖脂、β-葡聚糖、类胡萝卜素	[43-44]

红酵母种Red yeast species	活性成分及用途Active ingredients and uses	参考文献Reference
黏红酵母 R. glutinis	红色素、类胡萝卜素、多糖、辅酶Q₁₀、橄榄的软化、处理工业污水	[17,35⇓ -37]
胶红酵母 R. mucilaginosa	氨基酸、酶、番茄红素、β-胡萝卜素、虾青素、多种脂肪酸、多糖、化妆品成分、饲料添加剂	[15,19,23⇓ -25,38 -39]
圆红酵母 R. toruloides	类胡萝卜素、虾青素、油脂、倍半萜、脂肪酸酯、脂肪醇、化妆品成分	[28,40⇓ -42]
克氏红酵母 R. kratochvilovae	脂类、外糖脂、β-葡聚糖、类胡萝卜素	[43-44]

物种名称Organism name	菌种Strain	BioProject	测序水平Level	大小Size/Mb	Scaffolds	编码序列CDS
R. mucilaginosa	CYJ03	PRJNA506114	Contig	19.037 2	88	6301^[45]
R. mucilaginosa	KR	PRJNA435582	Scaffold	20.066 2	359	7059
R. toruloides	CGMCC 2.1609	PRJNA297267	Scaffold	33.389 7	365	9820^[46]
R. toruloides	CBS 14	PRJEB40807	Contig	20.534 9	3	9464^[47]
R. kratochvilovae	CBS 7436	PRJNA643234	Scaffold	21.685 7	357	-
R. kratochvilovae	VS II C KN 5	PRJNA644637	Scaffold	21.857 6	376	-
R. glutinis	ZHK	PRJNA605146	Scaffold	22.325 5	30	6774^[48]
R. glutinis	ATCC 204091	PRJNA59971	Scaffold	20.478 9	29^[49]	3359^[49]
R. babjevae	CBS 7808	PRJEB48745	Contig	21.862 4	3^[50]	7591^[50]
R. babjevae	DBVPG 8058	PRJEB48745	Contig	21.522 1	1^[50]	7481^[50]
R. paludigena	CM33	PRJNA491831	Scaffold	20.655 4	78	-
R. paludigena	P4R5	PRJNA732286	Scaffold	20.967 9	277	-

物种名称Organism name	菌种Strain	BioProject	测序水平Level	大小Size/Mb	Scaffolds	编码序列CDS
R. mucilaginosa	CYJ03	PRJNA506114	Contig	19.037 2	88	6301^[45]
R. mucilaginosa	KR	PRJNA435582	Scaffold	20.066 2	359	7059
R. toruloides	CGMCC 2.1609	PRJNA297267	Scaffold	33.389 7	365	9820^[46]
R. toruloides	CBS 14	PRJEB40807	Contig	20.534 9	3	9464^[47]
R. kratochvilovae	CBS 7436	PRJNA643234	Scaffold	21.685 7	357	-
R. kratochvilovae	VS II C KN 5	PRJNA644637	Scaffold	21.857 6	376	-
R. glutinis	ZHK	PRJNA605146	Scaffold	22.325 5	30	6774^[48]
R. glutinis	ATCC 204091	PRJNA59971	Scaffold	20.478 9	29^[49]	3359^[49]
R. babjevae	CBS 7808	PRJEB48745	Contig	21.862 4	3^[50]	7591^[50]
R. babjevae	DBVPG 8058	PRJEB48745	Contig	21.522 1	1^[50]	7481^[50]
R. paludigena	CM33	PRJNA491831	Scaffold	20.655 4	78	-
R. paludigena	P4R5	PRJNA732286	Scaffold	20.967 9	277	-

目标性状 Targeted trait	代谢工程策略 Metabolic engineering strategies	生物来源 Source organism	结果 Outcomes	参考文献 Reference
Limonene production	Overexpressed the limonene synthase, neryl pyrophosphate synthase/geranyl pyrophosphate synthase and the native hydroxy-methyl-glutaryl-CoA reductase	R. toruloides NP11	Produced a maximum limonene titer of 393.5 mg/L	[72]
CoQ₁₀, sterols, and phytoene accumulation	a T-DNA insertion in the CAR1 gene coding for phytoene desaturase	R. mucilaginosa C2.5t1	Significant decreases in cell density and fatty acids content, higher productions of phytoene, CoQ₁₀, and sterols	[73]
Fatty alcohol production	Two overexpression targets（ACL1 and ACC1）and two deletion targets（the acyltransferases DGA1 and LRO1）	R. toruloides IFO0880	1.8 to 4.4-fold increases to the fatty alcohol titer in culture tubes	[74]
Fatty acid ethyl esters production	Introduced various wax ester synthase genes from different sources, mutated bifunctional enzyme to abolish the DGAT activity	R. toruloides Δku70	Improved the FAEEs titer to 1.02 g/L	[76]
Fatty acid production	Overexpressed acetyl coenzyme A carboxylase（ACC1 carboxylase）gene and repressed 3-hydroxy 3-methylglutaryl reductase（HMG-CoA reductase）	R. mucilaginosa Y-1	Acombination of both inhibitor and inducer resulted in a 57% increase in lipid concentration	[78]
Carotenoid biosynthesis	Constructed vectors pZPK-CRT-1 and pZPK-CRT-2 with strong promoters PGPD and TADH2	R. toruloides NP11	The intracellular carotenoid content of the transformants increased by 30%	[81]