植物中UbiA膜结合型芳香族异戊烯基转移酶的研究进展

落艳娇; 王圆月; 庞永珍; 申国安; 郭宝林

doi:10.11913/PSJ.2095-0837.22147

植物中UbiA膜结合型芳香族异戊烯基转移酶的研究进展

1.
中国医学科学院，北京协和医学院药用植物研究所，中药生物活性物质与资源利用教育部重点实验室，北京 100193
2.
中国农业科学院北京畜牧兽医研究所，北京 100193

基金项目: 中国医学科学院医学与健康科技创新工程项目（2021-I2M-1-031）

详细信息

作者简介:
落艳娇（1993-），女，硕士研究生，研究方向为药用植物代谢及分子生物学（E-mail：luoyj1009@163.com）

通讯作者:
申国安: E-mail：gashen@implad.ac.cn

郭宝林: guobaolin010@163.com

中图分类号: Q943.2
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出版历程
- 收稿日期: 2022-09-14
- 修回日期: 2022-11-02
- 网络出版日期: 2023-05-05
- 刊出日期: 2023-04-29

Research progress of UbiA membrane-bound aromatic prenyltransferases in plants

1.
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicines, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China
2.
Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Funds: This work was supported by a grant from the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-031).

摘要

摘要:
UbiA膜结合型芳香族异戊烯基转移酶（Prenyltransferases，PT）可催化异戊烯基单元转移到芳香族母核上形成C-C（或C-O）键，在植物中参与合成重要的代谢产物，如泛醌、质体醌、叶绿素、生育酚等。植物中多种具有异戊烯基的芳香族次生代谢物也是该类酶作用的产物。异戊烯基的引入增加了天然产物结构多样性和生物活性。本文介绍了植物中UbiA家族的基本类型，归纳了57个已鉴定功能的与次生代谢物（类黄酮、香豆素、二苯乙烯等）合成相关的UbiA PTs底物选择性、催化特点及其与初生代谢相关PTs的系统发育关系，并对异戊烯基转移酶基因的挖掘策略，以及利用微生物代谢工程定向合成活性异戊烯基化合物的应用前景进行了展望。
- 异戊烯基转移酶 /
- 初生代谢 /
- 次生代谢 /
- 生物合成
Abstract:
UbiA membrane-bound aromatic prenyltransferases (UbiA PTs) catalyze the transfer of prenyl moieties to aromatic acceptor molecules to form C-C or C-O bonds, and participate in the biosynthesis of important plant chemicals, including ubiquinone, plastoquinone, chlorophyll, and tocopherol. A variety of aromatic secondary metabolites with prenyl groups in plants are also products of this class of enzyme. The introduction of prenyl groups increases the structural diversity and biological activity of natural products. In this paper, we introduce the basic types of UbiA families in plants, summarize the substrate selectivity and catalytic characteristics of 57 UbiA PTs related to biosynthesis of secondary metabolites (flavonoids, coumarins, stilbenes), and discuss their phylogenetic relationship with primary metabolism-related PTs. We also discuss the exploration strategies of prenyltransferase genes and the application prospects of targeted synthesis of active prenylated compounds by microbial metabolic engineering.
- Prenyltransferases /
- Primary metabolism /
- Secondary metabolism /
- Biosynthesis
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图 1 UbiA异戊烯基转移酶的分类、一般催化机制和供体的结构式

A：异戊二烯焦磷酸结构式；B：UbiA异戊烯基转移酶的一般催化机制；C：异戊烯基转移酶的分类。

Figure 1. Classification and general catalytic mechanism of UbiA prenyltransferases and structural formula of isoprenyl diphosphates

A: Structural formula of isoprenyl diphosphates; B: General catalytic mechanism of UbiA superfamily prenyltransferases; C: Classification of prenyltransferases.

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图 2 类黄酮结构式

A：一般类黄酮；B：查尔酮；C：紫檀烷。异戊烯基的一般取代位点标为红色。

Figure 2. Flavonoid structural formula

A: General flavonoids; B: Chalcone; C: Pterocarpan. General substitution site for prenyl is indicated in red.

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图 3 植物中UbiA膜结合型芳香族异戊烯基转移酶的系统发育树

Figure 3. Phylogenetic tree of UbiA membrane-bound aromatic prenyltransferases in plants

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表 1 植物类黄酮异戊烯基转移酶的催化特性

Table 1 Catalytic properties of flavonoid prenyltransferases in plants

物种名称 Species name	蛋白名称 Protein name	底物类型 Substrate type	底物名称 Substrate name	异戊烯基供体 Prenyl donor	异戊烯基取代位点 Prenyl substitution site	二价阳离子 Divalent cation	参考文献 References
苦参 Sophora flavescens Alt.	SfN8DT-1	二氢黄酮	Liquiritigenin>Naringenin> Hesperetin	DMAPP	A环C-8位	Mg^{2 +}	[7]
	SfiLDT	查尔酮	Isoliquiritigenin	DMAPP	未知	Mg^{2 +}	[33]
	SfG6DT	异黄酮	Genistein>Biochanina	DMAPP、GPP¹、FPP¹	A环C-6位	Mg^{2 +}>Ni^{2 +}> Mn^{2 +}>Ca^{2 +}	[33]
	SfFPT	二氢查尔酮	Phloretin	DMAPP、GPP²	A环C-3'位	Mg^{2 +}>Ba^{2 +}>Ca^{2 +}>Fe^{2 +}>Co^{2 +}>Cu^{2 +}>Zn^{2 +}>Mn^{2 +}	[28]
		二氢黄酮	Eriodictyol>Naringenin> Pinocembrin>Liquiritigenin> Hesperetin>Isosakuranetin> Steppogenin>Tsugafolin> Sakuranetin		A环C-8位
		黄酮	Chrysin		A环C-8位
		二氢黄酮醇	Taxifolin		A环C-8位
大豆 Glycine max (L.) Merr.	GmG4DT	紫檀烷	Glycinol>Maackiain	DMAPP	A环C-4位	Mg^{2 +}>Mn^{2 +}>Co^{2 +}	[30]
	GmG2DT	紫檀烷	Glycinol	DMAPP	A环C-2位	Mg^{2 +}>Mn^{2 +}	[29]
	GmPT01	紫檀烷	Glycinol	DMAPP	A环C-2位	Mg^{2 +}	[31]
	GmIDT1	异黄酮	Daidzein>Genistein	DMAPP	B环	Mg^{2 +}>Mn^{2 +}	[29]
	GmIDT2	异黄酮	Daidzein≈Genistein	DMAPP	A环	Mg^{2 +}>Mn^{2 +}	[29]
	GmIDT3	异黄酮	Daidzein、Genistein	DMAPP	未知	Mg^{2 +}	[31]
白羽扇豆 Lupinus albus L.	LaPT1	异黄酮	2-Hydroxygenistein> Genistein	DMAPP	B环C-3'位	Mg^{2 +}>Mn^{2 +}>Ni^{2 +}>Co^{2 +}>Zn^{2 +}>Ca^{2 +}	[34]
	LaPT2	黄酮醇	Kaempferol>Kaempferide>Quercetin>Galangin> Fesitin>Morin	DMAPP	A环C-8位	Mg^{2 +}	[12]
	LaPT2	二氢黄酮	Naringenin	DMAPP	未知	Mg^{2 +}
甘草 Glycyrrhiza uralensis Fisch.	GuA6DT	黄酮	Apigenin>Chrysin> Diosmtin>Luteolin> Norartocarpetin> Chrysoeroil	DMAPP、GPP¹	A环C-6位	Mg^{2 +}>Mn^{2 +}>Zn^{2 +}>Fe^{2 +}>Co^{2 +}>Ca^{2 +}>Ba^{2 +}	[11]
甘草 Glycyrrhiza uralensis Fisch.	GuILDT	查尔酮	2',4'-Dihydroxychalcone> Isoliquiritigenin> 2,4,2',4'-Tetrahydro-xychalcone> Naringeninchalcone	DMAPP	A环C-3'位	Mg^{2 +}>Co^{2 +}>Ni^{2 +}>Fe^{2 +}>Ba^{2 +}>Mn^{2 +}>Ca^{2 +}	[35]
百脉根 Lotus japonicus L.	LjG6DT	异黄酮	Genistein	DMAPP	A环C-6位	Mg^{2 +}>Co^{2 +}>Mn^{2 +}>Ca^{2 +}>Zn^{2 +}>Fe^{2 +}	[36]
补骨脂 Psoralea corylifolia (L.) Medik.	PcM4DT	紫檀烷	Maackiain>3-Hydroxy-9-methoxypterocarpan	DMAPP	A环C-4位	Mg^{2 +}>Mn^{2 +}>Co^{2 +}>Fe^{2 +}>Ba^{2 +}>Sr^{2 +}>Ca^{2 +}>Sn^{2 +}>Ni^{2 +}>Zn^{2 +}	[37]
桑 Morus alba L.	MaIDT	查尔酮	Isoliquiritigenin> 2',4'-Dihydroxychalcone> 2,4,2',4'-Tetrahydroxychalcone> Butein	DMAPP、GPP¹	A环C-3'位	Mg^{2 +}>Ba^{2 +}>Ca^{2 +}>Mn^{2 +}>Fe^{2 +}>Ni^{2 +}	[32]
		异黄酮	Genistein>2'-Hydroxygenistein		A环C-6位
		黄酮	Apigenin		A环C-6位
柘树 Cudrania tricuspidata (Carr.) Bur.	CtIDT	查尔酮	Isoliquiritigenin> 2,4,2',4'-Tetrahydroxychalcone> 2',4'-Dihydroxychalcone> Butein	DMAPP、GPP¹	A环C-3'位	Mg^{2 +}>Mn^{2 +}>Ca^{2 +}>Fe^{2 +}>Ba^{2 +}	[32]
柘树 Cudrania tricuspidata (Carr.) Bur.	CtIDT	异黄酮	2'-Hydroxygenistein> Genistein	DMAPP、GPP¹	A环C-6位	Mg^{2 +}>Mn^{2 +}>Ca^{2 +}>Fe^{2 +}>Ba^{2 +}
大麻 Cannabis sativa L.	CsPT3	黄酮	Chrysoeriol>Apigenin	DMAPP、GPP	A环C-6位	Mg^{2 +}	[38]
大麻 Cannabis sativa L.	CsPT8	黄酮	Apigenin	DMAPP	未知	Mg^{2 +}	[38]
啤酒花 Humulus lupulus L.	HlPT-1	查尔酮	Naringenin chalcone	DMAPP	A环C-3'位	Mg^{2 +}	[39]
柔毛淫羊藿 Epimedium pubescens Maxim.	EpPT8	黄酮醇	Kaempferol> Quercetin	DMAPP	A环C-8位	Mg^{2 +}	[40]
柔毛淫羊藿 Epimedium pubescens Maxim.	EpPT8	黄酮	Apigenin	DMAPP		Mg^{2 +}	[40]
箭叶淫羊藿 Epimedium sagittatum (Sieb. et Zucc.) Maxim.	EsPT2	黄酮醇	Kaempferol>Kaempferide	DMAPP	A环C-8位	Mg^{2 +}	[41]
箭叶淫羊藿 Epimedium sagittatum (Sieb. et Zucc.) Maxim.	EsPT2	二氢黄酮	Naringenin	DMAPP		Mg^{2 +}	[41]
注：“>”用于表示对底物的催化活性顺序；¹ 研究只证明提供了该供体与最适底物发生异戊烯基化反应；² GPP作为供体时，SfFPT仅催化pinocembrin，isosakuranetin和naringenin发生异戊烯基化反应。
Notes: “>” indicates order of catalytic activity to the substrate; ¹ Prenylation of the donor with an optimal substrate is demonstrated; ² SfFPT only catalyzed prenylation of pinocembrin, isosakuranetin, and naringenin when GPP was used as the prenyl donor.

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表 2 植物中香豆素异戊烯基转移酶的催化特性

Table 2 Catalytic properties of coumarin prenyltransferases in plants

物种名称 Species name	蛋白名称 Protein name	底物名称 Substrate name	异戊烯基供体 Prenyl donor	异戊烯基取代位点 Prenyl substitution site	二价阳离子 Divalent cation	参考文献 References
欧芹Petroselinum crispum (Mill.) Hill	PcPT	Umbelliferone	DMAPP	C-6位>C-8位	Mg^{2 +}	[44]
欧防风Pastinaca sativa L.	PsPT1	Umbelliferone	DMAPP	C-6位>C-8位	Mg^{2 +}	[42]
欧防风Pastinaca sativa L.	PsPT2	Umbelliferone	DMAPP	C-8位>C-6位	Mg^{2 +}	[42]
柠檬Citrus limon (L.) Burm. F.	ClPT1	Umbelliferone>Esculetin>5,7-hydroxycoumarin >5-Methoxy-7-hydroxycoumarin	GPP	C-8位	Mg^{2 +}	[45]
无花果Ficus carica L.	FcPT1	Umbelliferone	DMAPP	C-6位	Mg^{2 +}	[46]
无花果Ficus carica L.	FcPT1	5-Methoxy-7-hydroxycoumarin	DMAPP	未知	Mg^{2 +}
葡萄柚Citrus paradisi Macf.	CpPT1	5,7-Dihydroxycoumarin, 8-Hydroxybergapten 5-Hydroxy-7-methoxycoumarin, Bergaptol,	GPP	5-OH或8-OH	Mg^{2 +}>Ni^{2 +}>Co^{2 +}>Mn^{2 +}>Zn^{2 +}>Ca^{2 +}	[47]
葡萄柚Citrus paradisi Macf.	CpPT3	Umbelliferone	GPP	C-8位	Mg^{2 +}	[47]
小苦橙Citrus micrantha Wester	CmiPT1a / b	Bergaptol和Xanthotoxol	GPP	5-OH或8-OH	Mg^{2 +}	[47]
明日叶Angelica keiskei (Miquel) Koidz.	AkPT1	Bergaptol和Xanthotoxol	DMAPP	5-OH或8-OH	Mg^{2 +}>Mn^{2 +}>Ca^{2 +}	[47]
大豆Glycine max (L.) Merr.	GmC4DT	Coumestrol	DMAPP	C-4位	Mg^{2 +}>Mn^{2 +}	[29]
九里香Murraya exotica L.	MePT1	Umbelliferone	GPP	C-8位、C-6位和7-OH	Mg^{2 +}	[48]

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参考文献(59)

[1]	Winkelblech J,Fan AL,Li SM. Prenyltransferases as key enzymes in primary and secondary metabolism[J]. Appl Microbiol Biotechnol,2015,99 (18):7379−7397. doi: 10.1007/s00253-015-6811-y
[2]	Yang YH,Ke N,Liu SX,Li WK. Structural and biochemical analysis of intramembrane prenyltransferases in the UbiA superfamiIy[J]. Methods Enzymol,2017,584:309−347.
[3]	Li WK. Bringing bioactive compounds into membranes:the UbiA superfamily of intramembrane aromatic prenyltransferases[J]. Trends Biochem Sci,2016,41 (4):356−370. doi: 10.1016/j.tibs.2016.01.007
[4]	Bonitz T,Alva V,Saleh O,Lupas AN,Heide L. Evolutionary relationships of microbial aromatic prenyltransferases[J]. PLoS One,2011,6 (11):e27336. doi: 10.1371/journal.pone.0027336
[5]	Young IG,Leppik RA,Hamilton JA,Gibson F. Biochemical and genetic studies on ubiquinone biosynthesis in Escherichia coli K-12:4-hydroxybenzoate octaprenyltransferase[J]. J Bacteriol,1972,110 (1):18−25. doi: 10.1128/jb.110.1.18-25.1972
[6]	Wang J,Chu SS,Zhu Y,Cheng H,Yu DY. Positive selection drives neofunctionalization of the UbiA prenyltransferase gene family[J]. Plant Mol Biol,2015,87 (4-5):383−394. doi: 10.1007/s11103-015-0285-2
[7]	Sasaki K,Mito K,Ohara K,Yamamoto H,Yazaki K. Cloning and characterization of naringenin 8-prenyltransferase,a flavonoid-specific prenyltransferase of Sophora flavescens[J]. Plant Physiol,2008,146 (3):1075−1084. doi: 10.1104/pp.107.110544
[8]	Bo ST, Chang SK, Zhu H, Jiang YM, Yang B. Naturally occurring prenylated stilbenoids: food sources, biosynthesis, applications and health benefits[J]. Crit Rev Food Sci Nutr, 2022. Doi: 10.1080/10408398.2022.2056131.
[9]	De Bruijn WJC,Levisson M,Beekwilder J,van Berkel WJH,Vincken JP. Plant aromatic prenyltransferases:tools for microbial cell factories[J]. Trends Biotechnol,2020,38 (8):917−934. doi: 10.1016/j.tibtech.2020.02.006
[10]	Marin M,Manez S. Recent trends in the pharmacological activity of isoprenyl phenolics[J]. Curr Med Chem,2013,20 (2):272−279. doi: 10.2174/092986713804806676
[11]	Li JH,Chen RD,Wang RS,Liu X,Xie D,et al. GuA6DT,a regiospecific prenyltransferase from Glycyrrhiza uralensis,catalyzes the 6-prenylation of flavones[J]. ChemBioChem,2014,15 (11):1673−1681. doi: 10.1002/cbic.201402160
[12]	Liu JY,Xia YY,Jiang WB,Shen GA,Pang YZ. LaPT2 gene encodes a flavonoid prenyltransferase in white lupin[J]. Front Plant Sci,2021,12:673337. doi: 10.3389/fpls.2021.673337
[13]	Okada K,Ohara K,Yazaki K,Nozaki K,Uchida N,et al. The AtPPT1 gene encoding 4-hydroxybenzoate polyprenyl diphosphate transferase in ubiquinone biosynthesis is required for embryo development in Arabidopsis thaliana[J]. Plant Mol Biol,2004,55 (4):567−577. doi: 10.1007/s11103-004-1298-4
[14]	Ohara K,Yamamoto K,Hamamoto M,Sasaki K,Yazaki K. Functional characterization of OsPPT1,which encodes p-hydroxybenzoate polyprenyltransferase involved in ubiquinone biosynthesis in Oryza sativa[J]. Plant Cell Physiol,2006,47 (5):581−590. doi: 10.1093/pcp/pcj025
[15]	Yazaki K,Kunihisa M,Fujisaki T,Sato F. Geranyl diphosphate:4-hydroxybenzoate geranyltransferase from Lithospermum erythrorhizon:cloning and characterization of a key enzyme in Shikonin biosynthesis[J]. J Biol Chem,2002,277 (8):6240−6246. doi: 10.1074/jbc.M106387200
[16]	Ohara K,Muroya A,Fukushima N,Yazaki K. Functional characterization of LePGT1,a membrane-bound prenyltransferase involved in the geranylation of p-hydroxybenzoic acid[J]. Biochem J,2009,421 (2):231−241. doi: 10.1042/BJ20081968
[17]	Wang S,Wang RS,Liu T,Zhan ZL,Kang LP,et al. Production of 3-geranyl-4-hydroxybenzoate acid in yeast,an important intermediate of Shikonin biosynthesis pathway[J]. FEMS Yeast Res,2017,17 (7):fox065.
[18]	Venkatesh TV,Karunanandaa B,Free DL,Rottnek JM,Baszis SR,Valentin HE. Identification and characterization of an Arabidopsis homogentisate phytyltransferase paralog[J]. Planta,2006,223 (6):1134−1144. doi: 10.1007/s00425-005-0180-1
[19]	Sadre R,Gruber J,Frentzen M. Characterization of homogentisate prenyltransferases involved in plastoquinone-9 and tocochromanol biosynthesis[J]. FEBS Lett,2006,580 (22):5357−5362. doi: 10.1016/j.febslet.2006.09.002
[20]	Tian L,DellaPenna D,Dixon RA. The pds2 mutation is a lesion in the Arabidopsis homogentisate solanesyltransferase gene involved in plastoquinone biosynthesis[J]. Planta,2007,226 (4):1067−1073. doi: 10.1007/s00425-007-0564-5
[21]	姚兴兰,王磊,张兰. 植物维生素E生物强化研究进展[J]. 生物技术进展,2020,10(5):479−486. doi: 10.19586/j.2095-2341.2020.0046 Yao XL,Wang L,Zhang L. Progress of vitamin E biofortification in plants[J]. Current Biotechnology,2020,10 (5):479−486. doi: 10.19586/j.2095-2341.2020.0046
[22]	Eckhardt U,Grimm B,Hörtensteiner S. Recent advances in chlorophyll biosynthesis and breakdown in higher plants[J]. Plant Mol Biol,2004,56 (1):1−14. doi: 10.1007/s11103-004-2331-3
[23]	Hederstedt L. Heme A biosynthesis[J]. Biochim Biophys Acta,2012,1817 (6):920−927. doi: 10.1016/j.bbabio.2012.03.025
[24]	Basset GJ,Latimer S,Fatihi A,Soubeyrand E,Block A. Phylloquinone (vitamin K1):occurrence,biosynthesis and functions[J]. Mini-Rev Med Chem,2017,17 (12):1028−1038.
[25]	Ming LG,Lv X,Ma XN,Ge BF,Zhen P,et al. The prenyl group contributes to activities of phytoestrogen 8-prenynaringenin in enhancing bone formation and inhibiting bone resorption in vitro[J]. Endocrinology,2013,154 (3):1202−1214. doi: 10.1210/en.2012-2086
[26]	Shi SC,Li JC,Zhao XM,Liu QB,Song SJ. A comprehensive review:biological activity,modification and synthetic methodologies of prenylated flavonoids[J]. Phytochemistry,2021,191:112895. doi: 10.1016/j.phytochem.2021.112895
[27]	Yang XM,Jiang YM,Yang JL,He JR,Sun J,et al. Prenylated flavonoids,promising nutraceuticals with impressive biological activities[J]. Trends Food Sci Technol,2015,44 (1):93−104. doi: 10.1016/j.jpgs.2015.03.007
[28]	Chen RD,Liu X,Zou JH,Yin YZ,Ou B,et al. Regio- and stereospecific prenylation of flavonoids by Sophora flavescens prenyltransferase[J]. Adv Synth Catal,2013,355 (9):1817−1828. doi: 10.1002/adsc.201300196
[29]	Yoneyama K,Akashi T,Aoki T. Molecular characterization of soybean pterocarpan 2-dimethylallyltransferase in glyceollin biosynthesis:local gene and whole-genome duplications of prenyltransferase genes led to the structural diversity of soybean prenylated isoflavonoids[J]. Plant Cell Physiol,2016,57 (12):2497−2509. doi: 10.1093/pcp/pcw178
[30]	Akashi T,Sasaki K,Aoki T,Ayabe S,Yazaki K. Molecular cloning and characterization of a cDNA for pterocarpan 4-dimethylallyltransferase catalyzing the key prenylation step in the biosynthesis of glyceollin,a soybean phytoalexin[J]. Plant Physiol,2009,149 (2):683−693. doi: 10.1104/pp.108.123679
[31]	Sukumaran A,McDowell T,Chen L,Renaud J,Dhaubhadel S. Isoflavonoid-specific prenyltransferase gene family in soybean:GmPT01,a pterocarpan 2-dimethylallyltransferase involved in glyceollin biosynthesis[J]. Plant J,2018,96 (5):966−981. doi: 10.1111/tpj.14083
[32]	Wang RS,Chen RD,Li JH,Liu X,Xie KB,et al. Molecular characterization and phylogenetic analysis of two novel regio-specific flavonoid prenyltransferases from Morus alba and Cudrania tricuspidata[J]. J Biol Chem,2014,289 (52):35815−35825. doi: 10.1074/jbc.M114.608265
[33]	Sasaki K,Tsurumaru Y,Yamamoto H,Yazaki K. Molecular characterization of a membrane-bound prenyltransferase specific for isoflavone from Sophora flavescens[J]. J Biol Chem,2011,286 (27):24125−24134. doi: 10.1074/jbc.M111.244426
[34]	Shen GA,Huhman D,Lei ZT,Snyder J,Sumner LW,Dixon RA. Characterization of an isoflavonoid-specific prenyltransferase from Lupinus albus[J]. Plant Physiol,2012,159 (1):70−80. doi: 10.1104/pp.112.195271
[35]	Li JH,Chen RD,Wang RS,Liu X,Xie KB,et al. Biocatalytic access to diverse prenylflavonoids by combining a regiospecific C-prenyltransferase and a stereospecific chalcone isomerase[J]. Acta Pharm Sin B,2018,8 (4):678−686. doi: 10.1016/j.apsb.2018.01.009
[36]	Liu JY,Jiang WB,Xia YY,Wang XM,Shen GA,Pang YZ. Genistein-specific G6DT gene for the inducible production of wighteone in Lotus japonicus[J]. Plant Cell Physiol,2018,59 (1):128−141. doi: 10.1093/pcp/pcx167
[37]	He JB,Dong ZY,Hu ZM,Kuang Y,Fan JR,et al. Regio-specific prenylation of pterocarpans by a membrane-bound prenyltransferase from Psoralea corylifolia[J]. Org Biomol Chem,2018,16 (36):6760−6766. doi: 10.1039/C8OB01724G
[38]	Rea KA,Casaretto JA,Al-Abdul-Wahid MS,Sukumaran A,Geddes-Mcalister J,et al. Biosynthesis of cannflavins A and B from Cannabis sativa L.[J]. Phytochemistry,2019,164:162−171. doi: 10.1016/j.phytochem.2019.05.009
[39]	Tsurumaru Y,Sasaki K,Miyawaki T,Uto Y,Momma T,et al. HlPT-1,a membrane-bound prenyltransferase responsible for the biosynthesis of bitter acids in hops[J]. Biochem Biophys Res Commun,2012,417 (1):393−398. doi: 10.1016/j.bbrc.2011.11.125
[40]	Shen G,Luo Y,Yao Y,Meng G,Zhang Y,et al. The discovery of a key prenyltransferase gene assisted by a chromosome-level Epimedium pubescens genome[J]. Front Plant Sci,2022,13:1034943.
[41]	Wang PP,Li CJ,Li XD,Huang WJ,Wang Y,et al. Complete biosynthesis of the potential medicine icaritin by engineered Saccharomyces cerevisiae and Escherichia coli[J]. Sci Bull,2021,66 (18):1906−1916. doi: 10.1016/j.scib.2021.03.002
[42]	Munakata R,Olry A,Karamat F,Courdavault V,Sugiyama A,et al. Molecular evolution of parsnip (Pastinaca sativa) membrane-bound prenyltransferases for linear and/or angular furanocoumarin biosynthesis[J]. New Phytol,2016,211 (1):332−344. doi: 10.1111/nph.13899
[43]	Venugopala KN,Rashmi V,Odhav B. Review on natural coumarin lead compounds for their pharmacological activity[J]. Biomed Res Int,2013,2013:963248.
[44]	Karamat F,Olry A,Munakata R,Koeduka T,Sugiyama A,et al. A coumarin-specific prenyltransferase catalyzes the crucial biosynthetic reaction for furanocoumarin formation in parsley[J]. Plant J,2014,77 (4):627−638. doi: 10.1111/tpj.12409
[45]	Munakata R,Inoue T,Koeduka T,Karamat F,Olry A,et al. Molecular cloning and characterization of a geranyl diphosphate-specific aromatic prenyltransferase from lemon[J]. Plant Physiol,2014,166 (1):80−90. doi: 10.1104/pp.114.246892
[46]	Munakata R,Kitajima S,Nuttens A,Tatsumi K,Takemura T,et al. Convergent evolution of the UbiA prenyltransferase family underlies the independent acquisition of furanocoumarins in plants[J]. New Phytol,2020,225 (5):2166−2182. doi: 10.1111/nph.16277
[47]	Munakata R,Olry A,Takemura T,Tatsumi K,Ichino T,et al. Parallel evolution of UbiA superfamily proteins into aromatic O-prenyltransferases in plants[J]. Proc Natl Acad Sci USA,2021,118 (17):e2022294118. doi: 10.1073/pnas.2022294118
[48]	Li N,Liu X,Zhang ML,Zhang ZK,Zhang BB,et al. Characterization of a coumarin C-/O-prenyltransferase and a quinolone C-prenyltransferase from Murraya exotica[J]. Org Biomol Chem,2022,20 (28):5535−5542. doi: 10.1039/D2OB01054B
[49]	Li HX,Ban ZN,Qin H,Ma LY,King AJ,Wang GD. A heteromeric membrane-bound prenyltransferase complex from hop catalyzes three sequential aromatic prenylations in the bitter acid pathway[J]. Plant Physiol,2015,167 (3):650−659. doi: 10.1104/pp.114.253682
[50]	Fiesel T,Gaid M,Müller A,Bartels J,El-Awaad I,et al. Molecular cloning and characterization of a xanthone prenyltransferase from Hypericum calycinum cell cultures[J]. Molecules,2015,20 (9):15616−15630. doi: 10.3390/molecules200915616
[51]	Nagia M,Gaid M,Biedermann E,Fiesel T,El-Awaad I,et al. Sequential regiospecific gem-diprenylation of tetrahydroxyxanthone by prenyltransferases from Hypericum sp.[J]. New Phytol,2019,222 (1):318−334. doi: 10.1111/nph.15611
[52]	Akinwumi BC,Bordun KAM,Anderson HD. Biological activities of stilbenoids[J]. Int J Mol Sci,2018,19 (3):792. doi: 10.3390/ijms19030792
[53]	Yang TH,Fang LL,Sanders S,Jayanthi S,Rajan G,et al. Stilbenoid prenyltransferases define key steps in the diversification of peanut phytoalexins[J]. J Biol Chem,2018,293 (1):28−46. doi: 10.1074/jbc.RA117.000564
[54]	Zhong ZH,Zhu W,Liu SZ,Guan QJ,Chen X,et al. Molecular characterization of a geranyl diphosphate-specific prenyltransferase catalyzing stilbenoid prenylation from Morus alba[J]. Plant Cell Physiol,2018,59 (11):2214−2227.
[55]	Munakata R,Takemura T,Tatsumi K,Moriyoshi E,Yanagihara K,et al. Isolation of Artemisia capillaris membrane-bound di-prenyltransferase for phenylpropanoids and redesign of artepillin C in yeast[J]. Commun Biol,2019,2:384. doi: 10.1038/s42003-019-0630-0
[56]	Saeki H,Hara R,Takahashi H,Iijima M,Munakata R,et al. An aromatic farnesyltransferase functions in biosynthesis of the anti-HIV meroterpenoid daurichromenic acid[J]. Plant Physiol,2018,178 (2):535−551. doi: 10.1104/pp.18.00655
[57]	Luo XZ,Reiter MA,D’Espaux L,Wong J,Denby CM,et al. Complete biosynthesis of cannabinoids and their unnatural analogues in yeast[J]. Nature,2019,567 (7746):123−126. doi: 10.1038/s41586-019-0978-9
[58]	Marsafari M,Samizadeh H,Rabiei B,Mehrabi A,Koffas M,Xu P. Biotechnological production of flavonoids:an update on plant metabolic engineering,microbial Host selection,and genetically encoded biosensors[J]. Biotechnol J,2020,15 (8):1900432. doi: 10.1002/biot.201900432
[59]	Levisson M,Araya-Cloutier C,de Bruijn WJC,van Der Heide M,Salvador López JM,et al. Toward developing a yeast cell factory for the production of prenylated flavonoids[J]. J Agric Food Chem,2019,67 (49):13478−13486. doi: 10.1021/acs.jafc.9b01367