UGT86C11 is a novel plant UDP-glycosyltransferase involved in labdane diterpene biosynthesis

Abstract

Glycosyltransferases constitute a large family of enzymes across all domains of life, but knowledge of their biochemical function remains largely incomplete, particularly in the context of plant specialized metabolism. The labdane diterpenes represent a large class of phytochemicals with many pharmacological benefits, such as anti-inflammatory, hepatoprotective, and anticarcinogenic. The medicinal plant kalmegh (Andrographis paniculata) produces bioactive labdane diterpenes; notably, the C19-hydroxyl diterpene (andrograpanin) is predominantly found as C19-O-glucoside (neoandrographolide), whereas diterpenes having additional hydroxylation(s) at C3 (14-deoxy-11,12-didehydroandrographolide) or C3 and C14 (andrographolide) are primarily detected as aglycones, signifying scaffold-selective C19-O-glucosylation of diterpenes in planta. Here, we analyzed UDP-glycosyltransferase (UGT) activity and diterpene levels across various developmental stages and tissues and found an apparent correlation of UGT activity with the spatiotemporal accumulation of neoandrographolide, the major diterpene C19-O-glucoside. The biochemical analysis of recombinant UGTs preferentially expressed in neoandrographolide-accumulating tissues identified a previously uncharacterized UGT86 member (ApUGT12/UGT86C11) that catalyzes C19-O-glucosylation of diterpenes with strict scaffold selectivity. ApUGT12 localized to the cytoplasm and catalyzed diterpene C19-O-glucosylation in planta. The substrate selectivity demonstrated by the recombinant ApUGT12 expressed in plant and bacterium hosts was comparable to native UGT activity. Recombinant ApUGT12 showed significantly higher catalytic efficiency using andrograpanin compared with 14-deoxy-11,12-didehydroandrographolide and trivial activity using andrographolide. Moreover, ApUGT12 silencing in plants led to a drastic reduction in neoandrographolide content and increased levels of andrograpanin. These data suggest the involvement of ApUGT12 in scaffold-selective C19-O-glucosylation of labdane diterpenes in plants. This knowledge of UGT86 function might help in developing plant chemotypes and synthesis of pharmacologically relevant diterpenes. Glycosyltransferases constitute a large family of enzymes across all domains of life, but knowledge of their biochemical function remains largely incomplete, particularly in the context of plant specialized metabolism. The labdane diterpenes represent a large class of phytochemicals with many pharmacological benefits, such as anti-inflammatory, hepatoprotective, and anticarcinogenic. The medicinal plant kalmegh (Andrographis paniculata) produces bioactive labdane diterpenes; notably, the C19-hydroxyl diterpene (andrograpanin) is predominantly found as C19-O-glucoside (neoandrographolide), whereas diterpenes having additional hydroxylation(s) at C3 (14-deoxy-11,12-didehydroandrographolide) or C3 and C14 (andrographolide) are primarily detected as aglycones, signifying scaffold-selective C19-O-glucosylation of diterpenes in planta. Here, we analyzed UDP-glycosyltransferase (UGT) activity and diterpene levels across various developmental stages and tissues and found an apparent correlation of UGT activity with the spatiotemporal accumulation of neoandrographolide, the major diterpene C19-O-glucoside. The biochemical analysis of recombinant UGTs preferentially expressed in neoandrographolide-accumulating tissues identified a previously uncharacterized UGT86 member (ApUGT12/UGT86C11) that catalyzes C19-O-glucosylation of diterpenes with strict scaffold selectivity. ApUGT12 localized to the cytoplasm and catalyzed diterpene C19-O-glucosylation in planta. The substrate selectivity demonstrated by the recombinant ApUGT12 expressed in plant and bacterium hosts was comparable to native UGT activity. Recombinant ApUGT12 showed significantly higher catalytic efficiency using andrograpanin compared with 14-deoxy-11,12-didehydroandrographolide and trivial activity using andrographolide. Moreover, ApUGT12 silencing in plants led to a drastic reduction in neoandrographolide content and increased levels of andrograpanin. These data suggest the involvement of ApUGT12 in scaffold-selective C19-O-glucosylation of labdane diterpenes in plants. This knowledge of UGT86 function might help in developing plant chemotypes and synthesis of pharmacologically relevant diterpenes. Plants make an astonishing diversity of chemicals that are important to their overall fitness in a challenging environment and are also valuable as pharmaceuticals and various industrial chemicals (1Pichersky E. Raguso R.A. Why do plants produce so many terpenoid compounds?.New Phytol. 2018; 220: 692-702Crossref PubMed Scopus (182) Google Scholar, 2Lacchini E. Goossens A. Combinatorial control of plant specialized metabolism: Mechanisms, functions, and consequences.Annu. Rev. Cell. Dev. Biol. 2020; 36: 291-313Crossref PubMed Scopus (15) Google Scholar, 3Erb M. Kliebenstein D.J. Plant secondary metabolites as defenses, regulators, and primary metabolites: The blurred functional trichotomy.Plant Physiol. 2020; 184: 39-52Crossref PubMed Google Scholar). The diversity in plant specialized pathway is believed to have originated because of the evolution of diverse enzyme function following gene duplication and neofunctionalization (4Fernie A.R. Tohge T. The genetics of plant metabolism.Annu. Rev. Genet. 2017; 51: 287-310Crossref PubMed Scopus (72) Google Scholar). A genome-wide analysis found about 15% of the protein-coding genes corresponds to the specialized metabolic pathways in plants (5Chae L. Kim T. Nilo-Poyanco R. Rhee S.Y. Genomic signatures of specialized metabolism in plants.Science. 2014; 344: 510-513Crossref PubMed Scopus (168) Google Scholar). Besides, the enzymes of the plant specialized metabolism often show catalytic promiscuity, leading to additional product diversity. The glycosyltransferases (GTs) detected in all forms of life catalyze the transfer of sugar moiety from activated sugar donors (e.g., nucleotide diphosphate/monophosphate sugar or lipid phosphate sugar) to various acceptor molecules, such as nucleotides, sugars, lipids, proteins, antibiotics, and metabolites functions, and Rev. PubMed Scopus Google Scholar, of functional diversity in family PubMed Scopus Google Scholar). the the family are The in of such as plant specialized metabolites are the the family in plants. family to in and of functional diversity in family PubMed Scopus Google Scholar). are also to as that as sugar of plant UGTs as sugar and are also by UGTs D.J. A class of plant glycosyltransferases in PubMed Scopus (182) Google Scholar, T. A. R. A. M. R. A. of to the enzyme family and sugar Cell. 2018; PubMed Scopus Google Scholar, A. R.A. is the major in Physiol. PubMed Scopus Google Scholar). Plant UGTs have the of to their important in the of relevant of and of of functional diversity in family PubMed Scopus Google Scholar, A. R.A. is the major in Physiol. PubMed Scopus Google Scholar, Glycosyltransferases of Rev. Plant Biol. PubMed Scopus Google Scholar, Plant secondary metabolism knowledge and PubMed Scopus Google Scholar, L. analysis of glycosyltransferases the of in plant PubMed Scopus Google Scholar, A. L. A. of and plant PubMed Scopus Google Scholar, M. A. from Biol. PubMed Scopus Google Scholar, A. T. M. R.A. A. Glycosyltransferases from in the of Biol. PubMed Scopus Google Scholar). The often a in the of their and A. A. T. R. R. in the synthesis of the major of PubMed Scopus Google Scholar, T. and in the diversity of Physiol. PubMed Scopus Google Scholar, in PubMed Scopus Google Scholar). the biochemical of UGTs to bioactive chemicals in plants to plant function and to A. L. A. of and plant PubMed Scopus Google Scholar, T. T. M. and in 2020; PubMed Scopus Google Scholar, an is in PubMed Scopus Google Scholar, of in major PubMed Scopus Google Scholar, L. L. a UDP-glycosyltransferase gene the to and accumulation in Plant 2020; PubMed Scopus Google Scholar, M. D.J. R. and of the and in metabolism in A. PubMed Scopus Google Scholar). a diversity of UGTs in a plant and the diversity of specialized metabolites in is to biochemical function of UGTs in plant specialized and about and but about UGTs are so and the native of many of the UGTs to of functional diversity in family PubMed Scopus Google Scholar, E. of by the and Cell. PubMed Scopus Google Scholar, A. The significantly to in Biol. PubMed Scopus Google Scholar). The labdane diterpenes a large family of phytochemicals with a of in The PubMed Scopus Google Scholar). These diterpenes represent a major of bioactive chemicals in the medicinal plant kalmegh (Andrographis paniculata) and from PubMed Scopus (168) Google Scholar, A. R. M. R. of a and plants the Rev. 2017; PubMed Scopus Google Scholar, R.A. an to 2020; Scopus Google Scholar, M. T. and major as PubMed Scopus Google Scholar, in and in by PubMed Scopus Google Scholar). a major bioactive diterpene C19-O-glucoside in anti-inflammatory, hepatoprotective, and A. of major of PubMed Scopus Google Scholar, M. of diterpenes of of PubMed Scopus Google Scholar, and in of PubMed Scopus Google Scholar, T. of and neoandrographolide in and PubMed Scopus Google Scholar, T. D.J. in 2017; PubMed Scopus Google Scholar). neoandrographolide showed the diterpene and a of of neoandrographolide A. of major of PubMed Scopus Google Scholar, T. D.J. in 2017; PubMed Scopus Google Scholar, of in activated in and by neoandrographolide from PubMed Scopus Google Scholar, L. A. from as a PubMed Scopus Google Scholar). in kalmegh with a diterpene catalyzed by the diterpene a diterpene to we have identified a diterpene the in the neoandrographolide pathway A. of an in accumulation of specialized diterpenes in PubMed Scopus Google Scholar, A. L. accumulation of medicinal PubMed Scopus Google Scholar). The in neoandrographolide C19-O-glucosylation of andrograpanin UGT in developmental and of neoandrographolide was UGTs and catalyzed in C19-O-glucosylation of but their involvement in of neoandrographolide was of the in neoandrographolide 2018; PubMed Scopus Google Scholar, L. M. M. of the medicinal plant the of the bioactive PubMed Scopus Google Scholar). the UGT in spatiotemporal of neoandrographolide, we have analyzed a data of kalmegh and identified UGTs that preferentially expressed in neoandrographolide-accumulating recombinant UGTs in UGT leading to the of ApUGT12 C19-O-glucosylation of diterpenes in a scaffold-selective The of an diterpene in and a correlation of ApUGT12 with UGT activity and neoandrographolide accumulation across various developmental stages and tissues a of ApUGT12 in the of diterpene C19-O-glucoside. spatiotemporal of we of diterpene and and diterpene and across developmental stages and using tissues and analysis of higher content of neoandrographolide, and 14-deoxy-11,12-didehydroandrographolide in and A and diterpenes detected in and neoandrographolide, and 14-deoxy-11,12-didehydroandrographolide also detected in in and The increased of neoandrographolide andrograpanin in kalmegh tissues of andrograpanin to neoandrographolide following in accumulation of andrograpanin and the higher content of and 14-deoxy-11,12-didehydroandrographolide the and C19-O-glucosylation of and 14-deoxy-11,12-didehydroandrographolide and A and These suggest that scaffold-selective C19-O-glucosylation to of diterpene and in planta. the involvement of UGT in diterpene UGT using of various and 14-deoxy-11,12-didehydroandrographolide the sugar whereas as sugar in C19-O-glucoside in was by UGT using andrograpanin as sugar acceptor higher enzyme activity in of and plants by in of plants and These tissues also higher of neoandrographolide UGT using of and neoandrographolide was detected in and UGT using 14-deoxy-11,12-didehydroandrographolide activity using andrograpanin C19-O-glucosylation of at a using of various higher UGT activity using andrograpanin and 14-deoxy-11,12-didehydroandrographolide might have to neoandrographolide at a higher and leading to of diterpene and in A and A and and the diterpene and additional at the C3 C14 suggest that scaffold-selective C19-O-glucosylation of diterpene by UGT to accumulation of diterpene and C19-O-glucosylation activity and neoandrographolide in various tissues showed a correlation A and The UGT activity andrograpanin C19-O-glucosylation was in of UGT activity was detected in neoandrographolide was detected at a higher in of whereas neoandrographolide detected in the enzyme in C19-O-glucosylation of a data of and and UGTs that preferentially expressed in identified A. L. accumulation of medicinal PubMed Scopus Google Scholar). The UGTs to the following a of to various the and in and was comparable The also found a of in and in tissues was of the in neoandrographolide 2018; PubMed Scopus Google Scholar, L. M. M. of the medicinal plant the of the bioactive PubMed Scopus Google Scholar). and to developmental and C19-O-glucosylation of and was by analysis and with diterpene accumulation and UGT activity and expressed at a higher in of plants and andrograpanin C19-O-glucosylation activity and neoandrographolide content in tissues or detected A and and that might a major in developmental and of diterpene Moreover, a catalytic efficiency of recombinant using and 14-deoxy-11,12-didehydroandrographolide activity of native UGT using diterpene aglycones, is to a major in diterpene C19-O-glucosylation of the in neoandrographolide 2018; PubMed Scopus Google Scholar). The of catalyzed the diterpene in the neoandrographolide showed a correlation with developmental and of neoandrographolide A. of an in accumulation of specialized diterpenes in PubMed Scopus Google Scholar, A. L. accumulation of medicinal PubMed Scopus Google Scholar). that UGT might also with in of The analysis of data identified UGT that expressed at a higher in neoandrographolide-accumulating in and of the in also M. of in the medicinal plant Plant PubMed Scopus Google Scholar). that or the analysis of in identified UGTs that the plant secondary product in of to the of UGTs and M. Plant secondary metabolism The functional Plant PubMed Scopus Google Scholar). UGTs of the diterpene pathway UGTs that in and pathways previously A. R.A. is the major in Physiol. PubMed Scopus Google Scholar, T. and in the diversity of Physiol. PubMed Scopus Google Scholar, T. T. M. and in 2020; PubMed Scopus Google Scholar, an is in PubMed Scopus Google Scholar, E. of by the and Cell. PubMed Scopus Google Scholar, A. The significantly to in Biol. PubMed Scopus Google Scholar, M. of a enzyme in 2020; PubMed Scopus Google Scholar, of enzymes synthesis in PubMed Scopus Google Scholar, M. D.J. and biochemical of an Biol. PubMed Scopus Google Scholar). UGTs of kalmegh diterpene a analysis was using The analysis are with UGTs of and pathways These UGTs biochemical to their involvement in diterpene the the of UGTs using as and in the of recombinant in UGTs diterpene C19-O-glucosylation in using as sugar whereas and 14-deoxy-11,12-didehydroandrographolide as the sugar of E. recombinant UGTs and of recombinant UGTs following in UGT with andrograpanin as sugar and analysis of that as catalyzed C19-O-glucosylation of andrograpanin to neoandrographolide A and ApUGT12 was to following a in The of ApUGT12 was to the of the recombinant UGT was using and The product analyzed by C19-O-glucosylation of andrograpanin to neoandrographolide A and The of neoandrographolide in ApUGT12 was in to the of neoandrographolide and Besides, the recombinant ApUGT12 also catalyzed C19-O-glucosylation of 14-deoxy-11,12-didehydroandrographolide to produce was identified data in analysis A and ApUGT12 showed higher activity using andrograpanin 14-deoxy-11,12-didehydroandrographolide the ApUGT12 activity using as sugar acceptor and A and The and recombinant ApUGT12 in in a of and using andrograpanin substrate and The analysis that and are the and ApUGT12 activity. that ApUGT12 catalyzes C19-O-glucosylation of and at a catalyzed recombinant ApUGT12 catalyzed C19-O-glucosylation of andrograpanin to neoandrographolide analysis identified neoandrographolide in and ApUGT12 product but in using of E. with The was in at of neoandrographolide and andrograpanin the catalytic of of recombinant ApUGT12 using and ApUGT12 showed trivial activity using the using andrographolide. ApUGT12 a andrograpanin 14-deoxy-11,12-didehydroandrographolide and Moreover, andrograpanin was significantly higher 14-deoxy-11,12-didehydroandrographolide ApUGT12 about higher catalytic efficiency using andrograpanin using 14-deoxy-11,12-didehydroandrographolide The and 14-deoxy-11,12-didehydroandrographolide also and substrate of in using and a of phytochemicals to and such as and ApUGT12 of strict scaffold selectivity of ApUGT12 was expressed as in and in was with the help of a of at the or of ApUGT12 that might because of and of ApUGT12 as and an silencing was also to increased of or in A. of of PubMed Scopus Google Scholar). was detected in the cytoplasm and of in the cytoplasm of or or was with a A the transfer of to in 2018; Google Scholar). and in and or of and and The of ApUGT12 was because plants metabolites in and the of such metabolites is by their in cytoplasm functions, and Rev. PubMed Scopus Google Scholar, Glycosyltransferases of Rev. Plant Biol. PubMed Scopus Google Scholar). ApUGT12 catalyze in diterpene with andrograpanin. of of and analyzed by The neoandrographolide with that ApUGT12 catalyzed in C19-O-glucosylation of andrograpanin to produce neoandrographolide andrograpanin in neoandrographolide, that the UGT of catalyze C19-O-glucosylation of andrograpanin. in C19-O-glucosylation of and 14-deoxy-11,12-didehydroandrographolide was using of using of showed C19-O-glucosylation of andrograpanin to neoandrographolide and C19-O-glucosylation of 14-deoxy-11,12-didehydroandrographolide was also in at a andrograpanin C19-O-glucosylation and at a in using of suggest that ApUGT12 localized in the cytoplasm and catalyzed in diterpene the involvement of ApUGT12 in spatiotemporal of neoandrographolide, ApUGT12 in kalmegh tissues was by with increased UGT activity and neoandrographolide ApUGT12 expressed at an increased in of and plants A and and Besides, ApUGT12 expressed at a in tissues UGT activity and neoandrographolide such as in and Moreover, of ApUGT12 and increased UGT activity and neoandrographolide content in of plants a of ApUGT12 in of neoandrographolide and A and the of ApUGT12 UGT and neoandrographolide accumulation in various tissues suggest the involvement of ApUGT12 in spatiotemporal of the of ApUGT12 in of neoandrographolide, gene silencing was using M. R. and genes are to PubMed Scopus Google Scholar, R. gene silencing in PubMed Scopus Google Scholar, A. of gene silencing in an important medicinal PubMed Scopus Google Scholar). The of in was by of and to the of silencing was developing the in A. of gene silencing in an important medicinal PubMed Scopus Google Scholar). The of in of silencing led to reduction in ApUGT12 in analysis of metabolites in reduction in neoandrographolide an of ApUGT12 in the of major diterpene C19-O-glucoside and andrograpanin content in was increased significantly as compared with the control and The increased accumulation of andrograpanin in to of C19-O-glucosylation of andrograpanin to neoandrographolide because of ApUGT12 to content of neoandrographolide in was because of ApUGT12 and levels analyzed in levels of and in that silencing of ApUGT12 led to a reduction in neoandrographolide content in suggest a major of ApUGT12 in of UGTs are and about and the UGTs of and UGT such as and of ApUGT12 with the a analysis was using and UGTs M. genetics analysis across Biol. 2018; PubMed Scopus Google Scholar). the ApUGT12 was with the and UGT86 family and to ApUGT12 showed to the UGT to The biochemical function of and UGT86 family remains a plant UGT86 family member having about with catalyzed of in R. T. T. R. glycosyltransferases catalyze the of bioactive Physiol. 2020; 184: PubMed Scopus Google Scholar). ApUGT12 showed to with and also catalyzed andrograpanin C19-O-glucosylation of the in neoandrographolide 2018; PubMed Scopus Google Scholar, L. M. M. of the medicinal plant the of the bioactive PubMed Scopus Google Scholar). A of of and identified the plant secondary product and the catalytic and might their substrate L. R.A. of a from Cell. PubMed Scopus Google Scholar). the of ApUGT12 to of medicinal diterpene in plant but also knowledge biochemical function of a UGT86 family in plant specialized metabolism. represent of the enzyme and to of the protein-coding genes in plants functions, and Rev. PubMed Scopus Google Scholar, of functional diversity in family PubMed Scopus Google Scholar, D.J. A class of plant glycosyltransferases in PubMed Scopus (182) Google Scholar). The of catalyzed by the family in in plant and T. A. R. A. M. R. A. of to the enzyme family and sugar Cell. 2018; PubMed Scopus Google Scholar, A. R.A. is the major in Physiol. PubMed Scopus Google Scholar, A. L. A. of and plant PubMed Scopus Google Scholar, M. A. from Biol. PubMed Scopus Google Scholar, A. T. M. R.A. A. Glycosyltransferases from in the of Biol. PubMed Scopus Google Scholar, A. A. T. R. R. in the synthesis of the major of PubMed Scopus Google Scholar, T. and in the diversity of Physiol. PubMed Scopus Google Scholar, in PubMed Scopus Google Scholar, T. T. M. and in 2020; PubMed Scopus Google Scholar, an is in PubMed Scopus Google Scholar, A. M. R. E. of diterpene the of in Cell. PubMed Scopus Google Scholar). we have identified a previously uncharacterized UGT86 member (ApUGT12/UGT86C11) that catalyzed C19-O-glucosylation with strict scaffold selectivity and is in developmental and of bioactive labdane diterpenes in the medicinal plant The catalytic of recombinant ApUGT12 expressed in E. and was to the native UGT activity detected in kalmegh and The recombinant ApUGT12 significantly higher catalytic efficiency using andrograpanin 14-deoxy-11,12-didehydroandrographolide ApUGT12 showed activity using that the catalytic efficiency of ApUGT12 using andrograpanin is because of the increased substrate and increased of C19-O-glucosylation and at C3 C14 are found in andrograpanin we the that the at C3 C14 in diterpene scaffold to a drastic in of C19-O-glucosylation catalyzed by The analysis of ApUGT12 might scaffold-selective C19-O-glucosylation catalyzed by of recombinant expressed ApUGT12 was and in with sugar and sugar and as in the The data are the of in a expressed ApUGT12 was and in with sugar and sugar and as in the The data are the of UGTs and previously to catalyze in C19-O-glucosylation of andrograpanin to produce neoandrographolide of the in neoandrographolide 2018; PubMed Scopus Google Scholar, L. M. M. of the medicinal plant the of the bioactive PubMed Scopus Google Scholar). and have with ApUGT12 and to UGT and ApUGT12 of and to neoandrographolide but and show correlation with the developmental and of neoandrographolide A and A and and A and ApUGT12 was by but also showed a correlation with the developmental and of UGT activity and neoandrographolide content A and A and and A and ApUGT12 silencing led to of diterpenes in kalmegh plants showed significantly content of neoandrographolide and increased of substrate was detected in a that andrograpanin is a native substrate of ApUGT12 and that in function of ApUGT12 by the and and Moreover, the of recombinant ApUGT12 using various diterpene and the of diterpene and in tissues also that andrograpanin is a substrate of ApUGT12 in and and A and andrograpanin showed such as and the of is so because of in a from kalmegh from in the PubMed Scopus Google Scholar, M. A. R. and in the and biochemical of activity of andrograpanin from 2020; 36: PubMed Scopus Google Scholar). ApUGT12 silencing a to andrograpanin content in plants. a major of ApUGT12 in developmental and of major diterpene whereas UGTs and might to of diterpene C19-O-glucoside in to also showed a correlation with of neoandrographolide A. of an in accumulation of specialized diterpenes in PubMed Scopus Google Scholar). having in the ApUGT12 to function in the cytoplasm the diterpene pathway of kalmegh an of specialized metabolic are in and predominantly the E. Goossens A. Combinatorial control of plant specialized metabolism: Mechanisms, functions, and consequences.Annu. Rev. Cell. Dev. Biol. 2020; 36: 291-313Crossref PubMed Scopus (15) Google Scholar). diterpenes with about are a large family of in The PubMed Scopus Google Scholar). The the in labdane diterpene but the enzymes in the such as and the evolution of metabolism.Annu. Rev. Plant Biol. 2014; PubMed Scopus Google Scholar, A. M. diterpene metabolism in and functional of from PubMed Scopus Google Scholar, of bioactive in the medicinal plant 2018; PubMed Scopus Google Scholar, E. E. M. L. genes from pathways PubMed Scopus Google Scholar). to and to catalyze labdane diterpene in but the of UGT86 in diterpene was A. A. T. R. R. in the synthesis of the major of PubMed Scopus Google Scholar, of the in neoandrographolide 2018; PubMed Scopus Google Scholar, L. M. M. of the medicinal plant the of the bioactive PubMed Scopus Google Scholar, from and the of 2018; PubMed Scopus Google Scholar). ApUGT12 is a to the of UGT in diterpene UGT86 of the UGT in plants of functional diversity in family PubMed Scopus Google Scholar, L. analysis of glycosyltransferases the of in plant PubMed Scopus Google Scholar). a member of the UGT86 family was R. T. T. R. glycosyltransferases catalyze the of bioactive Physiol. 2020; 184: PubMed Scopus Google Scholar). of a substrate selectivity that UGT86 diverse in plant specialized metabolism. that ApUGT12 is to the kalmegh labdane diterpene pathway and substrate selectivity because a of phytochemicals to the and labdane diterpene and that to UGT86 that UGT86 family in in at UGT86 and showed UGT86 family in diverse plants a the diversity of function might in plants. the of ApUGT12 of the biochemical function of UGTs in plant specialized metabolism but also the of plants a diterpene plants in the the of to and plant stages as previously A. of an in accumulation of specialized diterpenes in PubMed Scopus Google Scholar). was to plants as previously and in Physiol. 2014; PubMed Scopus (72) Google Scholar). was in plant as previously and enzymes to diversity in the medicinal Phytol. PubMed Scopus Google Scholar). Plant in and at of proteins, and was as previously A. of but in and Phytol. 2017; PubMed Scopus Google Scholar). was using and using was in using with at The was by at the The was analyzed by following the and as the genes of data an analysis of of the genes and in analysis are in from using and and The of the was using The E. The at in and The secondary was using of primary and to an to was at The was at and of was at by and with and The was in with and in was by to and at The was at and to using of recombinant UGT in of UGT the of was to to at a with and with A. to of in Scopus Google Scholar). of ApUGT12 to of was to a with a and a The was in a using to and with The of recombinant and and using a The of was analyzed in with and was following the using A and the of of the of PubMed Scopus Google and also by at an at The of was also by analysis of with of using of ApUGT12 was and and ApUGT12 was using with and and following T. T. T. R. T. T. of in analysis of PubMed Scopus Google Scholar). and and by with and A. to of in Scopus Google Scholar). The recombinant in The by and following of using the Scholar). of recombinant in was in and and was as previously using to plants and enzymes to diversity in the medicinal Phytol. PubMed Scopus Google Scholar). a gene silencing was from with recombinant ApUGT12 A. of of PubMed Scopus Google Scholar). to of and a using of was at and detected in a of to whereas was at and detected in a of to A. to of in Scopus Google Scholar). The of and was by the previously in the function of the as with andrograpanin in UGT or ApUGT12 from the and using and in previously A. of gene silencing in an important medicinal PubMed Scopus Google Scholar). A. was in kalmegh at as previously with A. of gene silencing in an important medicinal PubMed Scopus Google Scholar). and in and an at to to in and to a of at and at to and in the silencing of and or of in to of kalmegh was as previously A. of gene silencing in an important medicinal PubMed Scopus Google Scholar). from was in and with and in to at to with a in a The at to of showed in but the have silencing A. of gene silencing in an important medicinal PubMed Scopus Google Scholar). the to of in and at from kalmegh tissues and in UGT to in using and and was in and at was by at and in using in UGT was in and sugar acceptor or and to of or of at to with at The was by the was by and in analysis using as a A. of an in accumulation of specialized diterpenes in PubMed Scopus Google or and analysis as ApUGT12 in or ApUGT12 the at from to in the in using to andrograpanin or and ApUGT12 in at The in to and andrograpanin. The product in the was with a to by and and by analysis and using of of the of using 14-deoxy-11,12-didehydroandrographolide was the of substrate in ApUGT12 activity phytochemicals and was analyzed in as ApUGT12 activity in was also as previously with M. M. A to metabolism and Physiol. 2017; PubMed Scopus Google Scholar). and in and was in and in plant of in in and at plant to in using and The was with The was by to and in to in and was with of plant metabolites and UGT was in an using a and a of a and as previously T. of bioactive from of the and of using 2014; PubMed Scopus Google Scholar). The of a of and with and The of neoandrographolide, and 14-deoxy-11,12-didehydroandrographolide and in at to and and was with a to the and analyzed as previously A the of from the PubMed Scopus Google Scholar, of and in and using Scholar, A. analysis and functional of of the 2020; PubMed Scopus Google Scholar). The with an was The of a a a a a and a The was an The was a with a at and at and of a with a 2020; Scholar). The of and and the was as to to to to to to and to the was using the at was in the from to with a at The was in and The and data using The of the as and The data by The was to at a of The was and analysis in the The data are in the with and This A. L. accumulation of medicinal PubMed Scopus Google Scholar). The that have of with the of The the and and the of and of and Plants and UGT is and and A. and R. M. data and and from the and the of and the

Topics & Concepts