Carotenoid biosynthetic pathway produces not only pigments that protect photosynthetic system against photo-oxidative damage, but also precursors of abscisic acid, the major hormone regulates stress responses. To unde...Carotenoid biosynthetic pathway produces not only pigments that protect photosynthetic system against photo-oxidative damage, but also precursors of abscisic acid, the major hormone regulates stress responses. To understand the response of carotenoid biosynthetic pathway to salt stress, the expression of the genes involved in carotenoid and ABA biosynthesis were compared in cultivated tomato Solanum lycopersicon cv. Moneymaker and its relative wild genotype S. pimpinellifolium (PI365967) together with the contents of carotenoids and ABA. The results showed that 11 of the 15 genes investigated were up-regulated and four unaltered in Moneymaker after 5 h of salt stress; whereas only four genes were up-regulated, four unaltered, and seven down-regulated in PI365967 after stress. Further comparison revealed that 11 salinity-induced genes were expressed significantly lower in Moneymaker than in PI365967 under normal condition, and 8 of them were induced to similar levels after salt stress. In consistence, ABA level was doubled in Moneymaker but kept consistent in PI365967 after salt stress, though the contents of neoxanthin, violaxanthin, [3-carotene, lutein, and total carotenoids were kept unchanged in both species. Since it is known that PI365967 is more tolerant to salt stress than Moneymaker, we proposed that the constitutive high level of carotenoid and ABA biosynthetic pathway under normal growth condition could be benefit to PI365967 for establishing the early response to salt stress. In addition, CrtR-bl and CrtR-b2 that encode [3-carotenoid hydroxylases were the only genes in carotenoid biosynthetic pathway that were up-regulated by salt stress in both species. The CrtR-b2 gene was cloned from both species and no essential difference was found in the encoded amino acid sequences. Transformation of CrtR-b2 to tobacco improved the seed germination under salt stress condition, indicating that the hydrolysis of β-carotenoid is the target of transcriptional regulation of the carotenoid biosynthesis in both tomato cultivar and wild relative.展开更多
Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum(P. falciparum) malaria although drug resistance has already emerged and spread i...Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum(P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria.展开更多
Danshen,the dried roots and rhizomes of Salvia miltiorrhiza Bunge(S.miltiorrhiza),is widely used in the treatment of cardiovascular and cerebrovascular diseases.Tanshinones,the bioactive compounds from Danshen,exhibit...Danshen,the dried roots and rhizomes of Salvia miltiorrhiza Bunge(S.miltiorrhiza),is widely used in the treatment of cardiovascular and cerebrovascular diseases.Tanshinones,the bioactive compounds from Danshen,exhibit a wide spectrum of pharmacological properties,suggesting their potential for future therapeutic applications.Tanshinone biosynthesis is a complex process involving at least six P450 enzymes that have been identified and characterized,most of which belong to the CYP76 and CYP71 families.In this study,CYP81C16,a member of the CYP71 clan,was identified in S.miltiorrhiza.An in vitro assay revealed that it could catalyze the hydroxylation of four para-quinone-type tanshinones,namely neocryptotanshinone,deoxyneocryptotanshinone,and danshenxinkuns A and B.SmCYP81C16 emerged as a potential broad-spectrum oxidase targeting the C-18 position of para-quinone-type tanshinones with an impressive relative conversion rate exceeding 90%.Kinetic evaluations and in vivo assays underscored its highest affinity towards neocryptotanshinone among the tested substrates.The overexpression of SmCYP81C16 promoted the accumulation of(iso)tanshinone in hairy root lines.The characterization of SmCYP81C16 in this study accentuates its potential as a pivotal tool in the biotechnological production of tanshinones,either through microbial or plant metabolic engineering.展开更多
De novo nucleotide biosynthetic pathway is a highly conserved and essential biochemical pathway in almost all organisms.Both purine nucleotides and pyrimidine nucleotides are necessary for cell metabolism and prolifer...De novo nucleotide biosynthetic pathway is a highly conserved and essential biochemical pathway in almost all organisms.Both purine nucleotides and pyrimidine nucleotides are necessary for cell metabolism and proliferation.Thus,the dysregulation of the de novo nucleotide biosynthetic pathway contributes to the development of many human diseases,such as cancer.It has been shown that many enzymes in this pathway are overactivated in different cancers.In this review,we summarize and update the current knowledge on the de novo nucleotide biosynthetic pathway,regulatory mechanisms,its role in tumorigenesis,and potential targeting opportunities.展开更多
The aim of our study was to assess differences in the expression of genes involved in fruit softening and ethylene biosynthetic pathways under different temperature storage conditions. Different peach cultivars of ‘X...The aim of our study was to assess differences in the expression of genes involved in fruit softening and ethylene biosynthetic pathways under different temperature storage conditions. Different peach cultivars of ‘Xiacui' and ‘Yumyeong', which are stonyhard, ‘Yinhualu', which is softmelting, ‘Hujing Milu', which is hard-melting, and ‘Baby Gold 6', which is non-melting at 80% ripening, were collected as test materials. The results showed that only slight ethylene production was detected after harvesting of ‘Yumyeong' and ‘Xiacui' under either a room temperature(25 °C) or low temperature(4 °C). The fruit firmness of stonyhard cultivars was retained at a high level under room temperature over time, whereas a low temperature induced ‘Yumyeong' fruit to soften. Quantitative real-time PCR results indicated that the PpACS1 gene was highly expressed in soft-melting, hard-melting and non-melting cultivars; however, expression was extremely low in stonyhard peaches. PpACS2 or PpACS3, however,was not detected in all five cultivars. Interestingly, cold treatment significantly decreased firmness along with endo-PG expression obviously upregulated in ‘Yumyeong', but not in ‘Xiacui' peaches. In conclusion, this study revealed that fruit softening of peaches with different flesh textures was closely related to ethylene biosynthesis during the storage period, which was controlled via regulating relevant gene expression levels under different storage temperatures.展开更多
Catharanthus roseus is one of the most extensively investigated medicinal plants, which can produce more than 130 alkaloids, including the powerful antitumor drugs vinblastine and vincristine. Here we review the recen...Catharanthus roseus is one of the most extensively investigated medicinal plants, which can produce more than 130 alkaloids, including the powerful antitumor drugs vinblastine and vincristine. Here we review the recent advances in the biosynthetic pathway of terpenoid indole alkaloids (TIAs) in C. roseus, and the identification and characterization of the corresponding enzymes involved in this pathway. Strictosidine is the central intermediate in the biosynthesis of different TIAs, which is formed by the condensation of secologanin and tryptamine. Secologanin is derived from terpenoid (isoprenoid) biosynthetic pathway, while tryptamine is derived from indole biosynthetic pathway. Then various specific end products are produced by different routes during downstream process. Although many genes and corresponding enzymes have been characterized in this pathway, our knowledge on the whole TIA biosynthetic pathway still remains largely unknown up to date. Full elucidation of TIA biosynthetic pathway is an important prerequisite to understand the regulation of the TIA biosynthesis in the medicinal plant and to produce valuable TIAs by synthetic biological technology.展开更多
Taxus,commonly known as yew,is a well-known gymnosperm with great ornamental and medicinal value.In this study,by assembling a chromosome-level genome of the Himalayan yew(Taxus wallichiana)with 10.9 Gb in 12 chromoso...Taxus,commonly known as yew,is a well-known gymnosperm with great ornamental and medicinal value.In this study,by assembling a chromosome-level genome of the Himalayan yew(Taxus wallichiana)with 10.9 Gb in 12 chromosomes,we revealed that tandem duplication acts as the driving force of gene family evolution in the yew genome,resulting in the main genes for paclitaxel biosynthesis,i.e.those encoding the taxadiene synthase,P450s,and transferases,being clustered on the same chromosome.The tandem duplication may also provide genetic resources for the nature to sculpt the core structure of taxoids at different positions and subsequently establish the complex pathway of paclitaxel by neofunctionalization.Furthermore,we confirmed that there are two genes in the cluster encoding isoenzymes of a known enzyme in the paclitaxel biosynthetic pathway.The reference genome of the Himalayan yew will serve as a platform for decoding the complete biosynthetic pathway of paclitaxel and understanding the chemodi-versity of taxoids in gymnosperms.展开更多
Diterpenoid alkaloids(DAs) have been often utilized in clinical practice due to their analgesic and anti-infammatory properties. Natural DAs are prevalent in the family Ranunculaceae, notably in the Aconitum genus. Ne...Diterpenoid alkaloids(DAs) have been often utilized in clinical practice due to their analgesic and anti-infammatory properties. Natural DAs are prevalent in the family Ranunculaceae, notably in the Aconitum genus. Nevertheless, the evolutionary origin of the biosynthesis pathway responsible for DA production remains unknown.In this study, we successfully assembled a highquality, pseudochromosome-level genome of the DA-rich species Aconitum vilmorinianum(A.vilmorinianum)(5.76 Gb). An A. vilmorinianumspecific whole-genome duplication event was discovered using comparative genomic analysis,which may aid in the evolution of the DA biosynthesis pathway. We identified several genes involved in DA biosynthesis via integrated genomic, transcriptomic, and metabolomic analyses. These genes included enzymes encoding target ent-kaurene oxidases and aminotransferases, which facilitated the activation of diterpenes and insertion of nitrogen atoms into diterpene skeletons, thereby mediating the transformation of diterpenes into DAs. The divergence periods of these genes in A. vilmorinianum were further assessed, and it was shown that two major types of genes were involved in the establishment of the DA biosynthesis pathway. Our integrated analysis offers fresh insights into the evolutionary origin of DAs in A.vilmorinianum as well as suggestions for engineering the biosynthetic pathways to obtain desired DAs.展开更多
Medicinal plants are renowned for their abundant production of secondary metabolites,which exhibit notable pharmacological activities and great potential for drug development.The biosynthesis of secondary metabolites ...Medicinal plants are renowned for their abundant production of secondary metabolites,which exhibit notable pharmacological activities and great potential for drug development.The biosynthesis of secondary metabolites is highly intricate and influenced by various intrinsic and extrinsic factors,resulting in substantial species diversity and content variation.Consequently,precise regulation of secondary metabolite synthesis is of utmost importance.In recent years,genome sequencing has emerged as a valuable tool for investigating the synthesis and regulation of secondary metabolites in medicinal plants,facilitated by the widespread use of high-throughput sequencing technologies.This review highlights the latest advancements in genome sequencing within this field and presents several strategies for studying secondary metabolites.Specifically,the article elucidates how genome sequencing can unravel the pathways for secondary metabolite synthesis in medicinal plants,offering insights into the functions and regulatory mechanisms of participating enzymes.Comparative analyses of plant genomes allow identification of shared pathways of metabolite synthesis among species,thereby providing novel avenues for obtaining cost-effective biosynthetic intermediates.By examining individual genomic variations,genes or gene clusters associated with the synthesis of specific compounds can be discovered,indicating potential targets and directions for drug development and the exploration of alternative compound sources.Moreover,the advent of gene-editing technology has enabled the precise modifications of medicinal plant genomes.Optimization of specific secondary metabolite synthesis pathways becomes thus feasible,enabling the precise editing of target genes to regulate secondary metabolite production within cells.These findings serve as valuable references and lessons for future drug development endeavors,conservation of rare resources,and the exploration of new resources.展开更多
Recognizing the composition and modulation of the microbiome, a viable therapeutic tool for multi-targeted therapy is a new strategy that has recently been explored. Glucosamine (GS) is being studied for its prebiotic...Recognizing the composition and modulation of the microbiome, a viable therapeutic tool for multi-targeted therapy is a new strategy that has recently been explored. Glucosamine (GS) is being studied for its prebiotic potential in addition to being the most abundant and naturally occurring amino monosaccharide. The current study focuses on glucosamine’s prebiotic potential by assessing the stability of various GS concentrations (1% - 5%) in the gastrointestinal tract (GIT) and its ability to be fermented by the gut microbiota. The results showed that GS stimulated the most growth in L. acidophilus even after a longer incubation time than B. bifidum and L. acidophilus growth was concentration-dependent, with maximum growth at 3% with a simultaneous decrease in pH (5.6 - 1.7). The decrease in GS concentration with time also represented the growth of bacterial species, demonstrating the species’ utilization of GS. Furthermore, at 3%, GS also represented the prebiotic index of 1.9. In addition, the concentration of GS in various simulated GIT fluids was estimated in both fast and fed conditions to examine GS stability at various levels in the gut. The results showed that GS remained unaffected and non-digestible in all of the simulated GIT fluids (salivary, gastric, intestinal, and colonic), but there was a slight decrease in GS concentration (2.8%) in the fasted state of gastric fluid due to low pH levels (1.6). As a result, the findings are conclusive and suggest that GS possesses prebiotic properties.展开更多
There are three non-allelic isogenes encoding phosphoribosylanthranilate isomerase (PAI) in Arabidopsis thaliana. The expression plasmids were constructed by fusion of the GUS reporter gene to the three PAI promoters ...There are three non-allelic isogenes encoding phosphoribosylanthranilate isomerase (PAI) in Arabidopsis thaliana. The expression plasmids were constructed by fusion of the GUS reporter gene to the three PAI promoters with or without the 5’ region encoding PAI N-terminal polypeptides and transferred into Arabidopsis plants by Agrobacterium tumefaciens. Analysis of GUS activity revealed that the PAI 5’ coding region was necessary for high expression of GUS activity. GUS activity in transgenic plants transformed with the expression plasmids containing the 5’ coding region of PAI1 or PAI3 was 60—100-fold higher than that without the corresponding 5’ region. However, the effect of 5’ coding region of PAI2 gene on the GUS activity was very small (only about 1 time difference). The GUS histochemical staining showed a similar result as revealed by GUS activity assay. It was expressed in the mesophyll cells and guard cells, but not in the epidermic cells, indicating that the N-terminal polypeptides encoded by展开更多
Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of d...Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor(HGF)/c-mesenchymal-epithelial transition receptor(c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microR NAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials.展开更多
Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions un...Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings re-garding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer’s disease, Parkinson’s disease, X-linked Charcot-Marie-Tooth disease, Peli-zaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.展开更多
Maca(Lepidium meyenii Walp.),a famous food supplement,has drawn an unprecedented international interest over the last two decades.It was assumed that glucosinolates,macamides,macaenes,and alkaloids are the main bioact...Maca(Lepidium meyenii Walp.),a famous food supplement,has drawn an unprecedented international interest over the last two decades.It was assumed that glucosinolates,macamides,macaenes,and alkaloids are the main bioactive components of Maca before.Recently,a series of novel thiohydantoins which generally exhibit a variety of activities have been isolated from Maca.This review focuses on the progress on the main bioactive components of Maca and their biosynthetic pathway,which indicates that macamides,thiohydantoins,and some alkaloids may originate from glucosinolates.Interestingly,thiohydantoins from Maca are the first type of thiohydantoin derivatives to be found from a natural source and may contribute to some significant effects of Maca.展开更多
Three new heptelidic acid derivatives(1-3)including two new dimeric esters and two known heptelidic acid analogues(4 and 5)were isolated from the solid culture of mushroom Lentinellus ursinus.The structures of new com...Three new heptelidic acid derivatives(1-3)including two new dimeric esters and two known heptelidic acid analogues(4 and 5)were isolated from the solid culture of mushroom Lentinellus ursinus.The structures of new compounds were confirmed by the analysis of NMR and HRESIMS spectroscopic data.The biosynthetic origin of compounds 1-5 was postulated.Compounds 1-5 exhibited no antibacterial activity against Staphylococcus aureus and Escherichia coli at the dose of 100 μM.展开更多
Pyrroloquinoline quinone (PQQ) is an important redox-active cofactor for many bacterial dehy-drogenases. It's biosynthetic pathway involves six or seven genes, one of which is pqqB. Former studies indicated that t...Pyrroloquinoline quinone (PQQ) is an important redox-active cofactor for many bacterial dehy-drogenases. It's biosynthetic pathway involves six or seven genes, one of which is pqqB. Former studies indicated that the protein encoded by pqqB, namely PqqB, functions as a PQQ transporter. Here we report the crystal structure of PqqB from Pseudomonas putida at 2.2 ? resolution together with functional studies to verify this theory.展开更多
Specialized plant metabolism is a rich resource of compounds for drug discovery.The acylated flavonoid glycoside melitidin is being developed as an anti-cholesterol statin drug candidate,but its biosynthetic route in ...Specialized plant metabolism is a rich resource of compounds for drug discovery.The acylated flavonoid glycoside melitidin is being developed as an anti-cholesterol statin drug candidate,but its biosynthetic route in plants has not yet been fully characterized.Here,we describe the gene discovery and functional characterization of a new flavonoid gene cluster(UDP-glucuronosyltransferases(Cg UGTs),1,2rhamnosyltransferase(Cg1,2Rha T),acyltransferases(Cg ATs))that is responsible for melitidin biosynthesis in pummelo(Citrus grandis(L.)Osbeck).Population variation analysis indicated that the tailoring of acyltransferases,specific for bitter substrates,mainly determine the natural abundance of melitidin.Moreover,3-hydroxy-3-methylglutaryl-Co A reductase enzyme inhibition assays showed that the product from this metabolic gene cluster,melitidin,may be an effective anti-cholesterol statin drug candidate.Co-expression of these clustered genes in Nicotiana benthamiana resulted in the formation of melitidin,demonstrating the potential for metabolic engineering of melitidin in a heterologous plant system.This study establishes a biosynthetic pathway for melitidin,which provides genetic resources for the breeding and genetic improvement of pummelo aimed at fortifying the content of biologically active metabolites.展开更多
AIM: To evaluate the qualitative and quantitativechanges in N-linked glycosylation, which occurredin association with diethyl nitrosamine-inducedhepatocellular carcinoma (HCC) in rodents.METHODS: Liver tissues of ...AIM: To evaluate the qualitative and quantitativechanges in N-linked glycosylation, which occurredin association with diethyl nitrosamine-inducedhepatocellular carcinoma (HCC) in rodents.METHODS: Liver tissues of (1) normal (non-tumorbearing)rats; and (2) tumor-bearing rats; were collectedand were used for histological and GlycanMap? analyses.Briefly, GlycanMap? analysis is a high-throughputassay that provides a structural and quantitativereadout of protein-associated glycans using a unique,automated 96-well assay technology coupled tomatrix-assisted laser desorption/ionization time-offlightmass spectrometry and custom bioinformatics.Histopathological studies were carried out to ensure thedevelopment of HCC in the tested animals.RESULTS: The N-glycomic analysis revealed 5glycans; Glc1Man9GlcNAc2, Gal2Man3GlcNac4Fuc1Neu1,Man4G l c N a c 2, G a l 2Man3G l c N a c 4Neu3OAc 3, andMan3GlcNac5Fuc1, which showed significant changesin rat HCC tissues when compared with normal livertissues. Four glycans were increased (P 〈 0.05) andGlc1Man9GlcNAc2 was decreased (5.89 ± 0.45 vs 3.54± 0.21, P 〈 0.01) in HCC tissues compared to normal liver tissues. An increase (66.5 ± 1.05 vs 62.7 ± 1.1,P 〈 0.05) in high-mannose structures in HCC rats wasobserved compared to normal rats. Importantly, HCCrats showed an increase (P 〈 0.05) in both tumorassociatedcarbohydrates and in branched glycans. Thechanges in glycans correlated well with glycan flowchanges reported in the glycan biosynthetic pathway,which indicates the importance of enzyme activitiesinvolved in glycan synthesis at different subcellularlocalizations.CONCLUSION: The reported HCC-associated changesin glycan flow and subcellular localization explain theincrease in high mannose glycans and siayl Lewisglycans common in HCC liver tissues.展开更多
Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy treatment.Nonetheless,despite the existence of a postulated biosynthetic pathway for more than half a century,the sp...Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy treatment.Nonetheless,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be identified.In this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine mescaline.We employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway elucidation.We identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in Peyote.Finally,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline production.Taken together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.展开更多
The Lamiaceae family is renowned for its terpenoid-based medicinal components,but Leonurus,which has traditional medicinal uses,stands out for its alkaloid-rich composition.Leonurine,the principal active compound foun...The Lamiaceae family is renowned for its terpenoid-based medicinal components,but Leonurus,which has traditional medicinal uses,stands out for its alkaloid-rich composition.Leonurine,the principal active compound found in Leonurus,has demonstrated promising effects in reducing blood lipids and treating strokes.However,the biosynthetic pathway of leonurine remains largely unexplored.Here,we present the chromosome-level genome sequence assemblies of Leonurus japonicus,known for its high leonurine production,and Leonurus sibiricus,characterized by very limited leonurine production.By integrating genomics,RNA sequencing,metabolomics,and enzyme activity assay data,we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase(ADC),uridine diphosphate glucosyltransferase(UGT),and serine carboxypeptidase-like(SCPL)acyltransferase enzymes that catalyze key reactions in this pathway.Further analyses revealed that the UGT–SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in L.japonicus,which contributed to the accumulation of leonurine specifically in L.japonicus.Collectively,our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.展开更多
基金supported by the Knowledge Innovation Key Program of the Chinese Academy of Sciences (KSCXZ-YW-N-013)
文摘Carotenoid biosynthetic pathway produces not only pigments that protect photosynthetic system against photo-oxidative damage, but also precursors of abscisic acid, the major hormone regulates stress responses. To understand the response of carotenoid biosynthetic pathway to salt stress, the expression of the genes involved in carotenoid and ABA biosynthesis were compared in cultivated tomato Solanum lycopersicon cv. Moneymaker and its relative wild genotype S. pimpinellifolium (PI365967) together with the contents of carotenoids and ABA. The results showed that 11 of the 15 genes investigated were up-regulated and four unaltered in Moneymaker after 5 h of salt stress; whereas only four genes were up-regulated, four unaltered, and seven down-regulated in PI365967 after stress. Further comparison revealed that 11 salinity-induced genes were expressed significantly lower in Moneymaker than in PI365967 under normal condition, and 8 of them were induced to similar levels after salt stress. In consistence, ABA level was doubled in Moneymaker but kept consistent in PI365967 after salt stress, though the contents of neoxanthin, violaxanthin, [3-carotene, lutein, and total carotenoids were kept unchanged in both species. Since it is known that PI365967 is more tolerant to salt stress than Moneymaker, we proposed that the constitutive high level of carotenoid and ABA biosynthetic pathway under normal growth condition could be benefit to PI365967 for establishing the early response to salt stress. In addition, CrtR-bl and CrtR-b2 that encode [3-carotenoid hydroxylases were the only genes in carotenoid biosynthetic pathway that were up-regulated by salt stress in both species. The CrtR-b2 gene was cloned from both species and no essential difference was found in the encoded amino acid sequences. Transformation of CrtR-b2 to tobacco improved the seed germination under salt stress condition, indicating that the hydrolysis of β-carotenoid is the target of transcriptional regulation of the carotenoid biosynthesis in both tomato cultivar and wild relative.
基金supported by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (CHEMAL, TDR/WHO)the National Science and Technology Development Agency of Thailand (NSTDA Career Development Award)+2 种基金the Thailand Research Fund (TRF Basic Research)the Office of Higher Education Commission (OHEC University Staff Development Consortium)Graduate School and Faculty of Medicine, Chulalongkorn University, Thailand
文摘Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum(P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria.
基金This work was supported by the National Key R&D Program of China(Nos.2020YFA0908000,2018YFA0900600)the National Natural Science Foundation of China(Nos.82003904,81822046)+4 种基金the Fundamental Research Funds for the Central public welfare research institutes(No.ZZ13-YQ-083)a Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2021A04110)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202005)a key project at central government level(the ability to establish sustainable use of valuable Chinese medicine resources2060302,China).
文摘Danshen,the dried roots and rhizomes of Salvia miltiorrhiza Bunge(S.miltiorrhiza),is widely used in the treatment of cardiovascular and cerebrovascular diseases.Tanshinones,the bioactive compounds from Danshen,exhibit a wide spectrum of pharmacological properties,suggesting their potential for future therapeutic applications.Tanshinone biosynthesis is a complex process involving at least six P450 enzymes that have been identified and characterized,most of which belong to the CYP76 and CYP71 families.In this study,CYP81C16,a member of the CYP71 clan,was identified in S.miltiorrhiza.An in vitro assay revealed that it could catalyze the hydroxylation of four para-quinone-type tanshinones,namely neocryptotanshinone,deoxyneocryptotanshinone,and danshenxinkuns A and B.SmCYP81C16 emerged as a potential broad-spectrum oxidase targeting the C-18 position of para-quinone-type tanshinones with an impressive relative conversion rate exceeding 90%.Kinetic evaluations and in vivo assays underscored its highest affinity towards neocryptotanshinone among the tested substrates.The overexpression of SmCYP81C16 promoted the accumulation of(iso)tanshinone in hairy root lines.The characterization of SmCYP81C16 in this study accentuates its potential as a pivotal tool in the biotechnological production of tanshinones,either through microbial or plant metabolic engineering.
文摘De novo nucleotide biosynthetic pathway is a highly conserved and essential biochemical pathway in almost all organisms.Both purine nucleotides and pyrimidine nucleotides are necessary for cell metabolism and proliferation.Thus,the dysregulation of the de novo nucleotide biosynthetic pathway contributes to the development of many human diseases,such as cancer.It has been shown that many enzymes in this pathway are overactivated in different cancers.In this review,we summarize and update the current knowledge on the de novo nucleotide biosynthetic pathway,regulatory mechanisms,its role in tumorigenesis,and potential targeting opportunities.
基金supported by the Jiangsu Agriculture Science and Technology Innovation Fund[CX(14)2015]China Agriculture Research System(CARS-31)
文摘The aim of our study was to assess differences in the expression of genes involved in fruit softening and ethylene biosynthetic pathways under different temperature storage conditions. Different peach cultivars of ‘Xiacui' and ‘Yumyeong', which are stonyhard, ‘Yinhualu', which is softmelting, ‘Hujing Milu', which is hard-melting, and ‘Baby Gold 6', which is non-melting at 80% ripening, were collected as test materials. The results showed that only slight ethylene production was detected after harvesting of ‘Yumyeong' and ‘Xiacui' under either a room temperature(25 °C) or low temperature(4 °C). The fruit firmness of stonyhard cultivars was retained at a high level under room temperature over time, whereas a low temperature induced ‘Yumyeong' fruit to soften. Quantitative real-time PCR results indicated that the PpACS1 gene was highly expressed in soft-melting, hard-melting and non-melting cultivars; however, expression was extremely low in stonyhard peaches. PpACS2 or PpACS3, however,was not detected in all five cultivars. Interestingly, cold treatment significantly decreased firmness along with endo-PG expression obviously upregulated in ‘Yumyeong', but not in ‘Xiacui' peaches. In conclusion, this study revealed that fruit softening of peaches with different flesh textures was closely related to ethylene biosynthesis during the storage period, which was controlled via regulating relevant gene expression levels under different storage temperatures.
文摘Catharanthus roseus is one of the most extensively investigated medicinal plants, which can produce more than 130 alkaloids, including the powerful antitumor drugs vinblastine and vincristine. Here we review the recent advances in the biosynthetic pathway of terpenoid indole alkaloids (TIAs) in C. roseus, and the identification and characterization of the corresponding enzymes involved in this pathway. Strictosidine is the central intermediate in the biosynthesis of different TIAs, which is formed by the condensation of secologanin and tryptamine. Secologanin is derived from terpenoid (isoprenoid) biosynthetic pathway, while tryptamine is derived from indole biosynthetic pathway. Then various specific end products are produced by different routes during downstream process. Although many genes and corresponding enzymes have been characterized in this pathway, our knowledge on the whole TIA biosynthetic pathway still remains largely unknown up to date. Full elucidation of TIA biosynthetic pathway is an important prerequisite to understand the regulation of the TIA biosynthesis in the medicinal plant and to produce valuable TIAs by synthetic biological technology.
基金the National Key R&D Program of China(2020YFA0908000)National Science Fund for Excellent Young Scholars(31922047)+1 种基金Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(No.TSBICIP-KJGG-002)the China Postdoctoral Science Foundation(No.2019M661032)。
文摘Taxus,commonly known as yew,is a well-known gymnosperm with great ornamental and medicinal value.In this study,by assembling a chromosome-level genome of the Himalayan yew(Taxus wallichiana)with 10.9 Gb in 12 chromosomes,we revealed that tandem duplication acts as the driving force of gene family evolution in the yew genome,resulting in the main genes for paclitaxel biosynthesis,i.e.those encoding the taxadiene synthase,P450s,and transferases,being clustered on the same chromosome.The tandem duplication may also provide genetic resources for the nature to sculpt the core structure of taxoids at different positions and subsequently establish the complex pathway of paclitaxel by neofunctionalization.Furthermore,we confirmed that there are two genes in the cluster encoding isoenzymes of a known enzyme in the paclitaxel biosynthetic pathway.The reference genome of the Himalayan yew will serve as a platform for decoding the complete biosynthetic pathway of paclitaxel and understanding the chemodi-versity of taxoids in gymnosperms.
基金supported by funding from the CAS “Pioneer Hundred Talents” Program and Strategic Priority Research Program of the Chinese Academy of Sciences (XDB31000000) to Y.C.National Natural Science Foundation of China (Nos. 31960082, 32270395, and 31960096)Yunnan Fundamental Research Projects (No. 202101AS070021) to D.Z。
文摘Diterpenoid alkaloids(DAs) have been often utilized in clinical practice due to their analgesic and anti-infammatory properties. Natural DAs are prevalent in the family Ranunculaceae, notably in the Aconitum genus. Nevertheless, the evolutionary origin of the biosynthesis pathway responsible for DA production remains unknown.In this study, we successfully assembled a highquality, pseudochromosome-level genome of the DA-rich species Aconitum vilmorinianum(A.vilmorinianum)(5.76 Gb). An A. vilmorinianumspecific whole-genome duplication event was discovered using comparative genomic analysis,which may aid in the evolution of the DA biosynthesis pathway. We identified several genes involved in DA biosynthesis via integrated genomic, transcriptomic, and metabolomic analyses. These genes included enzymes encoding target ent-kaurene oxidases and aminotransferases, which facilitated the activation of diterpenes and insertion of nitrogen atoms into diterpene skeletons, thereby mediating the transformation of diterpenes into DAs. The divergence periods of these genes in A. vilmorinianum were further assessed, and it was shown that two major types of genes were involved in the establishment of the DA biosynthesis pathway. Our integrated analysis offers fresh insights into the evolutionary origin of DAs in A.vilmorinianum as well as suggestions for engineering the biosynthetic pathways to obtain desired DAs.
基金funded by the National Natural Science Foundation of China,grant number 81603221.
文摘Medicinal plants are renowned for their abundant production of secondary metabolites,which exhibit notable pharmacological activities and great potential for drug development.The biosynthesis of secondary metabolites is highly intricate and influenced by various intrinsic and extrinsic factors,resulting in substantial species diversity and content variation.Consequently,precise regulation of secondary metabolite synthesis is of utmost importance.In recent years,genome sequencing has emerged as a valuable tool for investigating the synthesis and regulation of secondary metabolites in medicinal plants,facilitated by the widespread use of high-throughput sequencing technologies.This review highlights the latest advancements in genome sequencing within this field and presents several strategies for studying secondary metabolites.Specifically,the article elucidates how genome sequencing can unravel the pathways for secondary metabolite synthesis in medicinal plants,offering insights into the functions and regulatory mechanisms of participating enzymes.Comparative analyses of plant genomes allow identification of shared pathways of metabolite synthesis among species,thereby providing novel avenues for obtaining cost-effective biosynthetic intermediates.By examining individual genomic variations,genes or gene clusters associated with the synthesis of specific compounds can be discovered,indicating potential targets and directions for drug development and the exploration of alternative compound sources.Moreover,the advent of gene-editing technology has enabled the precise modifications of medicinal plant genomes.Optimization of specific secondary metabolite synthesis pathways becomes thus feasible,enabling the precise editing of target genes to regulate secondary metabolite production within cells.These findings serve as valuable references and lessons for future drug development endeavors,conservation of rare resources,and the exploration of new resources.
文摘Recognizing the composition and modulation of the microbiome, a viable therapeutic tool for multi-targeted therapy is a new strategy that has recently been explored. Glucosamine (GS) is being studied for its prebiotic potential in addition to being the most abundant and naturally occurring amino monosaccharide. The current study focuses on glucosamine’s prebiotic potential by assessing the stability of various GS concentrations (1% - 5%) in the gastrointestinal tract (GIT) and its ability to be fermented by the gut microbiota. The results showed that GS stimulated the most growth in L. acidophilus even after a longer incubation time than B. bifidum and L. acidophilus growth was concentration-dependent, with maximum growth at 3% with a simultaneous decrease in pH (5.6 - 1.7). The decrease in GS concentration with time also represented the growth of bacterial species, demonstrating the species’ utilization of GS. Furthermore, at 3%, GS also represented the prebiotic index of 1.9. In addition, the concentration of GS in various simulated GIT fluids was estimated in both fast and fed conditions to examine GS stability at various levels in the gut. The results showed that GS remained unaffected and non-digestible in all of the simulated GIT fluids (salivary, gastric, intestinal, and colonic), but there was a slight decrease in GS concentration (2.8%) in the fasted state of gastric fluid due to low pH levels (1.6). As a result, the findings are conclusive and suggest that GS possesses prebiotic properties.
基金Project supported by the National Distinguished Young Scholar Grant
文摘There are three non-allelic isogenes encoding phosphoribosylanthranilate isomerase (PAI) in Arabidopsis thaliana. The expression plasmids were constructed by fusion of the GUS reporter gene to the three PAI promoters with or without the 5’ region encoding PAI N-terminal polypeptides and transferred into Arabidopsis plants by Agrobacterium tumefaciens. Analysis of GUS activity revealed that the PAI 5’ coding region was necessary for high expression of GUS activity. GUS activity in transgenic plants transformed with the expression plasmids containing the 5’ coding region of PAI1 or PAI3 was 60—100-fold higher than that without the corresponding 5’ region. However, the effect of 5’ coding region of PAI2 gene on the GUS activity was very small (only about 1 time difference). The GUS histochemical staining showed a similar result as revealed by GUS activity assay. It was expressed in the mesophyll cells and guard cells, but not in the epidermic cells, indicating that the N-terminal polypeptides encoded by
基金Supported by grants BIO2014-56092-R(MINECO and FEDER)No.P12-CTS-1507(Andalusian Government and FEDER)+1 种基金funds from group BIO-267(Andalusian Government)The“CIBER de Enfermedades Raras”is an initiative from the ISCIII(Spain)
文摘Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor(HGF)/c-mesenchymal-epithelial transition receptor(c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microR NAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials.
基金supported by the National Natural Science Foundation of China(General Program),No.81271293the National Science Foundation for Young Scientists of China,No.81000490
文摘Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings re-garding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer’s disease, Parkinson’s disease, X-linked Charcot-Marie-Tooth disease, Peli-zaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.
基金This research work was financially supported by NSFC project and YiKe R&D Project(KIB-20140708Q)as well as Foundation of Key Laboratory of Tobacco Chemistry of Yunnan Province(KCFZ-2017-1096)Foundation of State Key Laboratory of Phytochemistry and Plant Resources in West China(P2010-ZZ14).
文摘Maca(Lepidium meyenii Walp.),a famous food supplement,has drawn an unprecedented international interest over the last two decades.It was assumed that glucosinolates,macamides,macaenes,and alkaloids are the main bioactive components of Maca before.Recently,a series of novel thiohydantoins which generally exhibit a variety of activities have been isolated from Maca.This review focuses on the progress on the main bioactive components of Maca and their biosynthetic pathway,which indicates that macamides,thiohydantoins,and some alkaloids may originate from glucosinolates.Interestingly,thiohydantoins from Maca are the first type of thiohydantoin derivatives to be found from a natural source and may contribute to some significant effects of Maca.
基金supported by the National Natural Science Foundation of China(21472233 and 81673334).
文摘Three new heptelidic acid derivatives(1-3)including two new dimeric esters and two known heptelidic acid analogues(4 and 5)were isolated from the solid culture of mushroom Lentinellus ursinus.The structures of new compounds were confirmed by the analysis of NMR and HRESIMS spectroscopic data.The biosynthetic origin of compounds 1-5 was postulated.Compounds 1-5 exhibited no antibacterial activity against Staphylococcus aureus and Escherichia coli at the dose of 100 μM.
文摘Pyrroloquinoline quinone (PQQ) is an important redox-active cofactor for many bacterial dehy-drogenases. It's biosynthetic pathway involves six or seven genes, one of which is pqqB. Former studies indicated that the protein encoded by pqqB, namely PqqB, functions as a PQQ transporter. Here we report the crystal structure of PqqB from Pseudomonas putida at 2.2 ? resolution together with functional studies to verify this theory.
基金supported by the National Key R&D Program of China (2021YFA0909600)the National Science Fund for Distinguished Young Scholars of China (31625021 to J.L)+7 种基金the“111”Project (No.D20024)the Young Elite Scientists Sponsorship Program by CAST (2019QNRC001)the National Postdoctoral Program for Innovative Talents (BX20220097)the China Postdoctoral Science Foundation (2022M710991)the Hainan Provincial Natural Science Foundation of China (323MS019)the Hainan Postdoctoral Grant Project (2022-BH-14)the Hainan Provincial Academician Innovation Platform Project (HD-YSZX-202003,HD-YSZX-202004)the Hainan University Startup Fund (KYQD (ZR)1866,KYQD (ZR)1916)。
文摘Specialized plant metabolism is a rich resource of compounds for drug discovery.The acylated flavonoid glycoside melitidin is being developed as an anti-cholesterol statin drug candidate,but its biosynthetic route in plants has not yet been fully characterized.Here,we describe the gene discovery and functional characterization of a new flavonoid gene cluster(UDP-glucuronosyltransferases(Cg UGTs),1,2rhamnosyltransferase(Cg1,2Rha T),acyltransferases(Cg ATs))that is responsible for melitidin biosynthesis in pummelo(Citrus grandis(L.)Osbeck).Population variation analysis indicated that the tailoring of acyltransferases,specific for bitter substrates,mainly determine the natural abundance of melitidin.Moreover,3-hydroxy-3-methylglutaryl-Co A reductase enzyme inhibition assays showed that the product from this metabolic gene cluster,melitidin,may be an effective anti-cholesterol statin drug candidate.Co-expression of these clustered genes in Nicotiana benthamiana resulted in the formation of melitidin,demonstrating the potential for metabolic engineering of melitidin in a heterologous plant system.This study establishes a biosynthetic pathway for melitidin,which provides genetic resources for the breeding and genetic improvement of pummelo aimed at fortifying the content of biologically active metabolites.
基金Supported by National Research Foundation Grant No.UIRCA 2012-21832 for A.Amin
文摘AIM: To evaluate the qualitative and quantitativechanges in N-linked glycosylation, which occurredin association with diethyl nitrosamine-inducedhepatocellular carcinoma (HCC) in rodents.METHODS: Liver tissues of (1) normal (non-tumorbearing)rats; and (2) tumor-bearing rats; were collectedand were used for histological and GlycanMap? analyses.Briefly, GlycanMap? analysis is a high-throughputassay that provides a structural and quantitativereadout of protein-associated glycans using a unique,automated 96-well assay technology coupled tomatrix-assisted laser desorption/ionization time-offlightmass spectrometry and custom bioinformatics.Histopathological studies were carried out to ensure thedevelopment of HCC in the tested animals.RESULTS: The N-glycomic analysis revealed 5glycans; Glc1Man9GlcNAc2, Gal2Man3GlcNac4Fuc1Neu1,Man4G l c N a c 2, G a l 2Man3G l c N a c 4Neu3OAc 3, andMan3GlcNac5Fuc1, which showed significant changesin rat HCC tissues when compared with normal livertissues. Four glycans were increased (P 〈 0.05) andGlc1Man9GlcNAc2 was decreased (5.89 ± 0.45 vs 3.54± 0.21, P 〈 0.01) in HCC tissues compared to normal liver tissues. An increase (66.5 ± 1.05 vs 62.7 ± 1.1,P 〈 0.05) in high-mannose structures in HCC rats wasobserved compared to normal rats. Importantly, HCCrats showed an increase (P 〈 0.05) in both tumorassociatedcarbohydrates and in branched glycans. Thechanges in glycans correlated well with glycan flowchanges reported in the glycan biosynthetic pathway,which indicates the importance of enzyme activitiesinvolved in glycan synthesis at different subcellularlocalizations.CONCLUSION: The reported HCC-associated changesin glycan flow and subcellular localization explain theincrease in high mannose glycans and siayl Lewisglycans common in HCC liver tissues.
基金fellowships from the Israel Ministry of Absorption and the Dean of the Plant Science Department in the Weizmann Institute.We thank Prof.David Nelson(University of Tennessee,USA)for the systematic naming of the cytochrome P450 enzymes characterized in this studyShmuel Regev and The Regev Nursery(Beit Elazari,Israel)for help in differentiating among Lophophora species+2 种基金Dr.Ziv Spiegelman for providing several N.benthamiana plantsXINTEZA(https://xinteza.com/)for funding this researchand the Adelis Foundation,the Leona M.and Harry B.Helmsley Charitable Trust,the Jeanne and Joseph Nissim Foundation for Life Sciences,Tom and Sondra Rykoff Family Foundation Research,Ron Sklare and the Raymond Burton Plant Genome Research Fund for supporting the A.A.laboratory。
文摘Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy treatment.Nonetheless,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be identified.In this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine mescaline.We employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway elucidation.We identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in Peyote.Finally,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline production.Taken together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.
基金supported by the National Natural Science Foundation of China(32170349 to P.X.)the Chenshan Special Fund for the Shanghai Landscaping Administration Bureau Program(G232402 to P.X.)the Ministry of Science and Technology of the People's Republic of China(YDZX20223100001003 to Y.-H.H.).
文摘The Lamiaceae family is renowned for its terpenoid-based medicinal components,but Leonurus,which has traditional medicinal uses,stands out for its alkaloid-rich composition.Leonurine,the principal active compound found in Leonurus,has demonstrated promising effects in reducing blood lipids and treating strokes.However,the biosynthetic pathway of leonurine remains largely unexplored.Here,we present the chromosome-level genome sequence assemblies of Leonurus japonicus,known for its high leonurine production,and Leonurus sibiricus,characterized by very limited leonurine production.By integrating genomics,RNA sequencing,metabolomics,and enzyme activity assay data,we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase(ADC),uridine diphosphate glucosyltransferase(UGT),and serine carboxypeptidase-like(SCPL)acyltransferase enzymes that catalyze key reactions in this pathway.Further analyses revealed that the UGT–SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in L.japonicus,which contributed to the accumulation of leonurine specifically in L.japonicus.Collectively,our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.