全局性调控因子LaeA在丝状真菌中的作用：机制与应用

doi:10.19586/j.2095-2341.2024.0105

生物技术进展 ›› 2025, Vol. 15 ›› Issue (1): 27-34.DOI: 10.19586/j.2095-2341.2024.0105

全局性调控因子LaeA在丝状真菌中的作用：机制与应用

孟宪超¹^,²(), 胡波¹, 宁哲¹, 孙园园¹, 于豪冰¹, 刘小宇¹()

^1.海军军医大学海军特色医学中心，上海　200433
^2.江苏海洋大学海洋食品与生物工程学院，江苏连云港　222005

收稿日期:2024-05-22 接受日期:2024-06-22 出版日期:2025-01-25 发布日期:2025-03-07
通讯作者: 刘小宇
作者简介:孟宪超 E-mail: 1239319990@qq.com；
基金资助:
国家重点研发计划项目(2022YFC2804105)

The Role of the Global Regulatory Factor LaeA in Filamentous Fungi: Mechanisms and Applications

Xianchao MENG¹^,²(), Bo HU¹, Zhe NING¹, Yuanyuan SUN¹, Haobing YU¹, Xiaoyu LIU¹()

^1.Naval Medical Center，Naval Medical University，Shanghai 200433，China
^2.School of Ocean Food and Biological Engineering，Jiangsu Ocean University，Jiangsu Lianyungang 222005，China

Received:2024-05-22 Accepted:2024-06-22 Online:2025-01-25 Published:2025-03-07
Contact: Xiaoyu LIU

摘要/Abstract

摘要：

LaeA是丝状真菌中重要的全局性调控因子，通过调节相关基因的表达，控制菌株的生长发育或促进次级代谢产物的合成。近年来，随着生物信息学分析技术的发展，LaeA参与的新的调控作用被发现。聚焦于LaeA的作用机制和调控作用，从LaeA的结构功能、真菌生育和次级代谢产物的调节3个方面综述了LaeA在真菌中的研究进展，同时探讨了LaeA在药物研发、农业以及工业生产等领域的应用潜力，以期为提高丝状真菌次级代谢产物的产量、活性和多样性，以及开发新型的海洋药物等提供参考和借鉴。

关键词: 全局性调控因子LaeA, 次级代谢, 丝状真菌

Abstract:

Loss of aflR expression-A （LaeA） has been recognized as a crucial global regulatory factor in filamentous fungi， orchestrating the intricate balance of gene expression to govern either the developmental trajectory of strains or the synthesis and diversification of secondary metabolites. Recent advancements in bioinformatics analysis have unveiled numerous novel regulatory roles of LaeA. This review focused on elucidating the mechanisms and regulatory functions of LaeA， encompassing its structural-functional attributes and its modulation of fungal growth and secondary metabolite biosynthesis. Simultaneously， it explored the potential applications of LaeA in the fields such as drug development， agriculture， and industrial production， in order to provide reference and help in improving the yield and activity of secondary metabolites of filamentous fungi，and developing new marine drugs.

Key words: global regulator LaeA, secondary metabolism, filamentous fungi

中图分类号:

孟宪超, 胡波, 宁哲, 孙园园, 于豪冰, 刘小宇. 全局性调控因子LaeA在丝状真菌中的作用：机制与应用[J]. 生物技术进展, 2025, 15(1): 27-34.

Xianchao MENG, Bo HU, Zhe NING, Yuanyuan SUN, Haobing YU, Xiaoyu LIU. The Role of the Global Regulatory Factor LaeA in Filamentous Fungi: Mechanisms and Applications[J]. Current Biotechnology, 2025, 15(1): 27-34.

图/表 6

参考文献 53

1	BOK J W, KELLER N P. LaeA, a regulator of secondary metabolism in Aspergillus spp.‍[J]. Eukaryot. Cell, 2004, 3(2): 527-535.
2	YU J, HAN H, ZHANG X, et al.. Discovery of two new sorbicillinoids by overexpression of the global regulator LaeA in a marine-derived fungus Penicillium dipodomyis YJ-11[J/OL]. Mar. Drugs, 2019, 17(8): 446[2024-09-02]. .
3	FENG Y, YIN Z, WU Y, et al.. LaeA controls virulence and secondary metabolism in apple canker pathogen Valsa mali [J/OL]. Front. Microbiol., 2020, 11: 581203[2024-09-02]. .
4	FERNANDES M, KELLER N P, ADAMS T H. Sequence-specific binding by Aspergillus nidulans AflR, a C6 zinc cluster protein regulating mycotoxin biosynthesis[J]. Mol. Microbiol., 1998, 28(6): 1355-1365.
5	周峰.橘青霉全局性调控因子LaeA相互作用蛋白研究[D].重庆:西南大学,2014.
6	章冰心, 温帅, 秦雪怡, 等.过表达LaeA激活海洋土曲霉中异黄素普辛类化合物的合成及其抗弧菌活性研究[J]. 菌物学报, 2023, 42(2): 562-569.
	ZHANG B X, WEN S, QIN X Y, et al.. Activating biosynthesis by overexpressing LaeA and anti-Vibrio activity of dihydroisoflavipucines of marine-derived Aspergillus terreus [J]. Mycosystema., 2023, 42(2): 562-569.
7	WANG G, ZHANG H, WANG Y, et al.. Requirement of LaeA, VeA, and VelB on asexual development, ochratoxin A biosynthesis, and fungal virulence in Aspergillus ochraceus [J/OL]. Front. Microbiol., 2019, 10: 2759[2024-09-02]. .
8	DING Z, WANG X, KONG F D, et al.. Overexpression of global regulator Talae1 leads to the discovery of new antifungal polyketides from endophytic fungus Trichoderma afroharzianum [J/OL]. Front. Microbiol., 2020, 11: 622785[2024-09-02]. .
9	汪滢,杨占山,鲍大鹏,等.全局调控因子LaeA对蛹虫草生长发育和次生代谢的作用[J].食用菌学报,2022,29(1):20-26.
	WANG Y, YANG Z S, BAO D P, et al.. Effects of LaeA on growth, development and secondary metabolism of Cordyceps militaris [J]. Acta Edulis Fungi, 2022, 29(1): 20-26.
10	CHETTRI P, BRADSHAW R E. LaeA negatively regulates dothistromin production in the pine needle pathogen Dothistroma septosporum [J]. Fungal Genet. Biol., 2016, 97: 24-32.
11	郑跃亮,曹双,黄宇琪,等.过表达全局调控因子LaeA对橘青霉美伐他汀的合成及产孢的影响[J].微生物学报,2014,54(12):1438-1445.
	ZHENG Y L, CAO S, HUANG Y Q, et al.. Overexpression of LaeA enhances mevastatin production and reduces sporulation of Penicillium citrinum [J]. Acta Microbiol. Sin., 2014, 54(12): 1438-1445.
12	MOTOYAMA T, YUN C S, OSADA H. Biosynthesis and biological function of secondary metabolites of the rice blast fungus Pyricularia oryzae [J/OL]. J. Ind. Microbiol. Biotechnol., 2021, 48(9-10): kuab058[2024-09-02]. .
13	KUMAR D, BARAD S, CHEN Y, et al.. LaeA regulation of secondary metabolism modulates virulence in Penicillium expansum and is mediated by sucrose[J]. Mol. Plant Pathol., 2017, 18(8): 1150-1163.
14	张久祎,李洁,薛鲜丽,等.柠檬酸工业生产菌黑曲霉TNA09基因敲除体系的构建[J].食品研究与开发,2022,43(3):164-171.
	ZHANG J Y, LI J, XUE X L, et al.. Construction of A gene knockout system in an industrial citric acid producing strain of Aspergillus niger TNA09[J]. Food Res. Dev., 2022, 43(3): 164-171.
15	STRAUSS J, REYES-DOMINGUEZ Y. Regulation of secondary metabolism by chromatin structure and epigenetic codes[J]. Fungal Genet. Biol., 2011, 48(1): 62-69.
16	MAOR U, BARDA O, SADHASIVAM S, et al.. Functional roles of LaeA, polyketide synthase, and glucose oxidase in the regulation of ochratoxin A biosynthesis and virulence in Aspergillus carbonarius [J]. Mol. Plant Pathol., 2021, 22(1): 117-129.
17	SAHA P, GHOSH S, ROY-BARMAN S. MoLAEA regulates secondary metabolism in Magnaporthe oryzae [J/OL]. mSphere, 2020, 5(2): e00936-19[2024-10-15]. .
18	CHANG P K, SCHARFENSTEIN L L, EHRLICH K C, et al.. Effects of laeA deletion on Aspergillus flavus conidial development and hydrophobicity may contribute to loss of aflatoxin production[J]. Fungal Biol., 2012, 116(2): 298-307.
19	HE T, WANG Y, DU L, et al.. Overexpression of global regulator LaeA induced secondary metabolite production in Aspergillus versicolor 0312[J]. Rec. Nat. Prod., 2020, 14(6): 387-394.
20	BAYRAM O, KRAPPMANN S, NI M, et al.. VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism[J]. Science, 2008, 320(5882): 1504-1506.
21	ZHANG C, LIANG J, ZHANG A, et al.. Overexpression of monacolin K biosynthesis genes in the Monascus purpureus azaphilone polyketide pathway[J]. J. Agric. Food Chem., 2019, 67(9): 2563-2569.
22	ZHAO Z, GU S, LIU D, et al.. The putative methyltransferase LaeA regulates mycelium growth and cellulase production in Myceliophthora thermophila [J/OL]. Biotechnol. Biofuels Bioprod., 2023, 16(1): 58[2024-09-02]. .
23	KHAN I, XIE W L, YU Y C, et al.. Heteroexpression of Aspergillus nidulanslaeA in marine-derived fungi triggers upregulation of secondary metabolite biosynthetic genes[J/OL]. Mar. Drugs, 2020, 18(12): 652[2024-09-02]. .
24	SARIKAYA BAYRAM O, BAYRAM O, VALERIUS O, et al.. LaeA control of velvet family regulatory proteins for light-dependent development and fungal cell-type specificity[J/OL]. PLoS Genet., 2010, 6(12): e1001226[2024-09-02]. .
25	BAYRAM Ö, BRAUS G H. Coordination of secondarymetabolism and development in fungi: the velvet familyof regulatory proteins[J]. FEMS Microbiol. Rev., 2012, 36(1): 1-24.
26	HOFF B, KAMEREWERD J, SIGL C, et al.. Two components of a velvet-like complex control hyphal morphogenesis, conidiophore development, and penicillin biosynthesis in Penicillium chrysogenum [J]. Eukaryot. Cell, 2010, 9(8): 1236-1250.
27	周国庆.冠突曲霉LaeA基因功能的研究[D].贵阳:贵州大学,2018.
28	ZHANG Y, WANG X, RAN Y, et al.. AfLaeA, a global regulator of mycelial growth, productionchlamydospore, pathogenicity, metabolismsecondary, and energy metabolism in the nematode-trapping fungus Arthrobotrys flagrans[J/OL]. Microbiol. Spectr., 2023, 11(4): e0018623[2024-09-02]. .
29	BOK J W, BALAJEE S A, MARR K A, et al.. LaeA, a regulator of morphogenetic fungal virulence factors[J]. Eukaryot. Cell, 2005, 4(9): 1574-1582.
30	鲍龙飞.草酸青霉孢子发生和纤维素酶基因表达共调控机制研究[D].济南:山东大学,2014.
31	LINDE T, ZOGLOWEK M, LÜBECK M, et al.. The global regulator LaeA controls production of citric acid and endoglucanases in Aspergillus carbonarius [J]. J. Ind. Microbiol. Biotechnol., 2016, 43(8): 1139-1147.
32	徐瑞涛, 陈浩宇, 陈美榕, 等.LaeA调控黑曲霉形态发展、赭曲霉毒素合成和氧化耐受[J]. 食品研究与开发, 2019, 40(6): 179-185.
	XU R T, CHEN H Y, CHEN M R, et al.. Effects of LaeA protein on morphological development,ochratoxin biosyntnthesis and oxidative stress tolerance in Aspergillus niger [J]. Food Res. Dev., 2019, 40(6): 179-185.
33	杨昱丹.红色红曲菌M7中LaeA和Gcn5相互作用关系研究[D].武汉:华中农业大学,2021.
34	CHENG M, ZHAO S, LIN C, et al.. Requirement of LaeA for sporulation, pigmentation and secondary metabolism in Chaetomium globosum [J]. Fungal Biol., 2021, 125(4): 305-315.
35	BOK J W, NOORDERMEER D, KALE S P, et al.. Secondary metabolic gene cluster silencing in Aspergillus nidulans [J]. Mol. Microbiol., 2006, 61(6): 1636-1645.
36	张梦薇.过表达laeA和veA基因对黑曲霉生长和代谢的影响[D].天津:天津科技大学,2020.
37	PERRIN R M, FEDOROVA N D, BOK J W, et al.. Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA[J/OL]. PLoS Pathog., 2007, 3(4): e50[2024-09-02]. .
38	POMRANING K R, DAI Z, MUNOZ N, et al.. Itaconic acid production is regulated by LaeA in Aspergillus pseudoterreus [J/OL]. Metab. Eng. Commun., 2022, 15: e00203[2024-09-02]. .
39	WANG B, LI X, TABUDRAVU J, et al.. The chemical profile of activated secondary metabolites by overexpressing LaeA in Aspergillus niger [J/OL]. Microbiol. Res., 2021, 248: 126735[2024-09-02]. .
40	刘亚平.黄柄曲霉遗传转化体系的构建以及其调控基因LaeA功能的研究[D].武汉:华中科技大学,2020.
41	MOON H, LEE M-K, BOK I, et al.. Unraveling the gene regulatory networks of the global regulators VeA and LaeA in Aspergillus nidulans [J/OL]. Microbiol. Spectr., 2023, 11(2): e0016623[2024-09-02]. .
42	LAN N, YUE Q, AN Z, et al.. Apc.LaeA and Apc.VeA of the velvet complex govern secondary metabolism and morphological development in the echinocandin-producing fungus Aspergillus pachycristatus [J]. J. Ind. Microbiol. Biotechnol., 2020, 47(1): 155-168.
43	ZHOU Z Z, ZHU H J, YANG C L, et al.. Dalestones A and B, two anti-inflammatory cyclopentenones from Daldinia eschscholzii with an edited strong promoter for the global regulator LaeA-like gene[J]. Chin. J. Nat. Med., 2019, 17(5): 387-393.
44	HONG E J, KIM N K, LEE D, et al.. Overexpression of the laeA gene leads to increased production of cyclopiazonic acid in Aspergillus fumisynnematus [J]. Fungal Biol., 2015, 119(11): 973-983.
45	ZHENG Y, CAO S, HUANG Y, et al.. Overexpression of LaeA enhances mevastatin production and reduces sporulation of Penicillium citrinum [J]. Acta Microbiol. Sin., 2014, 54(12): 1438-1445.
46	LEE S S, LEE J H, LEE I. Strain improvement by overexpression of the laeA gene in Monascus pilosus for the production of Monascus-fermented rice[J]. J. Microbiol. Biotechnol., 2013, 23(7): 959-965.
47	ZHANG M, YANG Y, LI L, et al.. LaeA regulates morphological development and ochratoxin A biosynthesis in Aspergillus niger [J]. Mycotoxin Res., 2022, 38(4): 221-229.
48	KIM H K, LEE S, MJO S, et al.. Functional roles of FgLaeA in controlling secondary metabolism, sexual development, and virulence in Fusarium graminearum [J/OL]. PLoS One, 2013, 8(7): e68441[2024-09-02]. .
49	BUTCHKO R A, BROWN D W, BUSMAN M, et al.. Lae1 regulates expression of multiple secondary metabolite gene clusters in Fusarium verticillioides [J]. Fungal Genet. Biol., 2012, 49(8): 602-612.
50	NIU J, ARENTSHORST M, NAIR P D, et al.. Identification of a classical mutant in the industrial host Aspergillus niger by systems genetics: LaeA is required for citric acid production and regulates the formation of some secondary metabolites[J]. G3 Bethesda Md., 2015, 6(1): 193-204.
51	ZHANG G, YAN P, LENG D, et al.. Functional roles of LaeA-like genes in fungal growth, cellulase activity, and secondary metabolism in Pleurotus ostreatus [J/OL]. J. Fungi, 2022, 8(9): 902[2024-09-02]. .
52	ODA K, KOBAYASHI A, OHASHI S, et al.. Aspergillus oryzae laeA regulates kojic acid synthesis genes[J]. Biosci. Biotechnol. Biochem., 2011, 75(9): 1832-1834.
53	BAYRAM Ö S, DETTMANN A, KARAHODA B, et al.. Control of development, secondary metabolism and light-dependent carotenoid biosynthesis by the velvet complex of Neurospora crassa [J]. Genetics, 2019, 212(3): 691-710.

属名	基因	菌种	功能	参考文献
Aspergillus	LaeA	Aspergillus sp. Z5	SM, D, V, O	[10]
	LaeA	土曲霉 Aspergillus terreus	SM, V	[6]
	LaeA	黑曲霉 Aspergillus niger	SM, D	[11-14]
	LaeA	黄曲霉 Aspergillus flavipes	SM, D, V	[15]
	ACLaeA	碳黑曲霉 Aspergillus carbonarius	SM	[16]
	LaeA	假土曲霉 Aspergillus pseudoterreus	SM	[17]
	LaeA	紫红曲霉 Monascus purpureus	SM, D	[18]
	LaeA	赭曲霉 Aspergillus ochraceus	SM, D, V	[7]
	LaeA	杂色曲霉 Aspergillus versicolor	SM, D	[19]
Magnaporthe	MoLaeA	稻热病菌 Magnaporthe oryzae	SM, D, O	[20]
Valsa	LaeA	苹果黑腐皮壳 Valsa mali	SM, D	[3]
Penicillium	LaeA	双足青霉YJ-11 Penicillium dipodomyis YJ-11	SM, D	[2]
Chaetomium	CgLaeA	球毛壳菌 Chaetomium globosum	SM, D	[21]
Cordyceps	CmLaeA	蛹虫草菌 Cordyceps militaris	SM, D	[9]
Myceliophthora	LaeA	嗜热毁丝霉 Myceliophthora thermophila	SM, D	[22]
Ganoderma	LaeA	灵芝 Ganoderma lucidum	SM, D	[23]
Trichoderma	TaLae1	非洲哈茨木霉 Trichoderma afroharzianum	SM, V, D	[8]

属名	基因	菌种	功能	参考文献
Aspergillus	LaeA	Aspergillus sp. Z5	SM, D, V, O	[10]
	LaeA	土曲霉 Aspergillus terreus	SM, V	[6]
	LaeA	黑曲霉 Aspergillus niger	SM, D	[11-14]
	LaeA	黄曲霉 Aspergillus flavipes	SM, D, V	[15]
	ACLaeA	碳黑曲霉 Aspergillus carbonarius	SM	[16]
	LaeA	假土曲霉 Aspergillus pseudoterreus	SM	[17]
	LaeA	紫红曲霉 Monascus purpureus	SM, D	[18]
	LaeA	赭曲霉 Aspergillus ochraceus	SM, D, V	[7]
	LaeA	杂色曲霉 Aspergillus versicolor	SM, D	[19]
Magnaporthe	MoLaeA	稻热病菌 Magnaporthe oryzae	SM, D, O	[20]
Valsa	LaeA	苹果黑腐皮壳 Valsa mali	SM, D	[3]
Penicillium	LaeA	双足青霉YJ-11 Penicillium dipodomyis YJ-11	SM, D	[2]
Chaetomium	CgLaeA	球毛壳菌 Chaetomium globosum	SM, D	[21]
Cordyceps	CmLaeA	蛹虫草菌 Cordyceps militaris	SM, D	[9]
Myceliophthora	LaeA	嗜热毁丝霉 Myceliophthora thermophila	SM, D	[22]
Ganoderma	LaeA	灵芝 Ganoderma lucidum	SM, D	[23]
Trichoderma	TaLae1	非洲哈茨木霉 Trichoderma afroharzianum	SM, V, D	[8]

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全局性调控因子LaeA在丝状真菌中的作用：机制与应用

The Role of the Global Regulatory Factor LaeA in Filamentous Fungi: Mechanisms and Applications

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