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PubMed1976

Formation of 5alpha-reduced C19-steroids from progesterone in vitro by a pathway through 5alpha-reduced C21-steroids in ovaries of late prepubertal rats.

Ovarian homogenates from 10-150-day-old rats were incubated with [3H]progesterone and NADPH. Also, ovarian homogenates from 28-day-old rats were incubated for 5-180 min with either [14C]progesterone, [3H]5alpha-pregnane-3,20-dione or [14C]progesterone plus [3H]5alpha-pregnane-3,20-dione. Following incubation, radioactive metabolites were isolated, identified, and measured by column and paper chromatography, with derivative formation and recrystallizations to constant specific activity. Prepubertal ovaries (10, 20, and 28 days of age) converted 15-60% of progesterone to C21-17-hydroxysteroids and C19-steroids. At 40 and 150 days of age (postpubertal), the formation of these steroids decreased to less than 2%. At 10 and 150 days of age, the major C19-steroids formed from progesterone were androstenedione and testosterone. At 20 and 28 days of age, however, no accumulation of these C19-delta4-3ketosteroids was found (less than 0.1% of each), at which time the conversion of progesterone to 5alpha-reduced C19-steriods, such as androsterone and 5alpha-androstane-3alpha,17beta-diol, reached 30%. In ovaries of 28-day-old rats, the results from incubation studies for the detection of metabolic pathways indicated two biosynthetic pathways leading to 5alpha-reduced C19-steroids, one from progesterone via 5alpha-reduced C21 steroids, such as 3alpha-hydroxy-5alpha-pregnan-20-one and 3alpha,17alpha-dihydroxy-5alpha-pregnan-20-one, and a second via 17-hydroxyprogesterone, androstenedione, and testosterone. It seems that the active 5alpha-reduction of C19-delta4-3-ketosteroids and the formation of 5alpha-reduced C19-steroids by the pathway through 5alpha-reduced C21-steroids, are present in the ovaries of older prepubertal rats and may be the biological significance.

Androgens↗

PubMed2003

Plasma leptin and exercise: recent findings.

It is established that plasma leptin is associated with satiety and that leptin stimulates lipid metabolism, and increases energy expenditure. These effects implicate leptin as a major regulator of energy homeostasis, which may serve to limit excess energy storage. As plasma leptin concentrations are tightly coupled with fat mass in humans, decreases in adipose mass with weight loss coincide with decreased concentrations of circulating leptin. However, due to many confounding factors, the effects of exercise on circulating leptin are less clear. The data from investigations examining single exercise bouts suggest that serum leptin concentrations are unaltered by short duration (41 minutes or less), non-exhaustive exercise, but may be affected by short duration, exhaustive exercise. More convincingly, studies investigating long duration exercise bouts indicate that serum leptin concentrations are reduced with exercise durations ranging from one to multiple hours. These findings raise speculation that exercise-associated reductions in leptin may be due to alterations in nutrient availability or nutrient flux at the level of the adipocytes, the primary site of leptin production and secretion. Thus, one purpose of this review is to discuss the effects of exercise on circulating leptin concentrations with special emphasis on studies that have examined single exercise bouts that are associated with high levels of energy expenditure and energy deficit. In addition, a 'nutrient sensing pathway' (the hexosamine biosynthetic pathway), which regulates leptin gene expression, will be discussed as a possible mechanism by which exercise-induced energy deficit may modulate serum leptin concentrations.

Adipose Tissue↗

PubMed1992

Siblings of 21-hydroxylase deficiency (non-salt-losing) with aldosterone hypersecretion.

We describe siblings with the non-salt-losing form of 21-hydroxylase deficiency who had hypersecretion of aldosterone and plasma renin activity (PRA). Blood pressure and serum electrolytes in both cases were normal despite the aldosterone hypersecretion. Aldosterone secretion was elevated markedly with ACTH administration and with sodium deprivation and/or volume depletion during ACTH suppression by dexamethasone. With suppression by dexamethasone, aldosterone hypersecretion was decreased with lowering of the steroids proximal to the block in the biosynthetic pathway. However, urinary sodium excretion was decreased. These results suggest that the biosynthetic pathway for aldosterone production was preserved. Furthermore, aldosterone hypersecretion and high PRA may serve to compensate for the sodium loss which results in turn from the overproduction of the sodium-losing steroids, such as progesterone and 17 alpha-hydroxyprogesterone which are aldosterone antagonists.

Adolescent↗

PubMed1998

The panE gene, encoding ketopantoate reductase, maps at 10 minutes and is allelic to apbA in Salmonella typhimurium.

In Salmonella typhimurium, precursors to the pyrimidine moiety of thiamine are synthesized de novo by the purine biosynthetic pathway or the alternative pyrimidine biosynthetic (APB) pathway. The apbA gene was the first locus defined as required for function of the APB pathway (D. M. Downs and L. Petersen, J. Bacteriol. 176:4858-4864, 1994). Recent work showed the ApbA protein catalyzes the NADPH-specific reduction of ketopantoic acid to pantoic acid. This activity had previously been associated with the pantothenate biosynthetic gene panE. Although previous reports placed panE at 87 min on the Escherichia coli chromosome, we show herein that apbA and panE are allelic and map to 10 min on both the S. typhimurium and E. coli chromosomes. Results presented here suggest that the role of ApbA in thiamine synthesis is indirect since in vivo labeling studies showed that pantoic acid, the product of the ApbA-catalyzed reaction, is not a direct precursor to thiamine via the APB pathway.

Alcohol Oxidoreductases↗

PubMed2004

Marine toxins and nonmarine toxins: convergence or symbiotic organisms?

Bioactive marine natural products occur only rarely in nonmarine sources. The converse also is true. Divergent evolutionary pathways for the biosynthesis of bioactive secondary metabolites seem to be the rule. Marine biosynthetic pathways lead to a wide variety of different structural classes, among which polyethers, macrolides, terpenes, unusual amino acids/peptides, and alkaloids are notable. Nonmarine biosynthetic pathways also lead to a similar wide variety of structural classes. However, the structures are usually quite different from the marine analogues. The alkaloids of plants are notable, but again there appears little convergence between the marine and nonmarine alkaloids. However, tetrodotoxin, a remarkable, highly polar, marine alkaloid, does occur in various amphibians. The occurrence and possible origin of tetrodotoxin and congeners, including chiriquitoxin, and of the saxitoxin analogue zetekitoxin in amphibians are reviewed.

Alkaloids↗

PubMedDate not supplied

Evidence for a common precursor for alpha MSH and beta-endorphin in the intermediate lobe of the pituitary of the reptile Anolis carolinensis.

In order to investigate the biosynthesis of alpha MSH and beta-endorphin in a non-mammalian vertebrate, individual lizard intermediate pituitaries were incubated in complete medium containing a radioactive amino acid, using either a steady label or a pulse/chase protocol. Following incubation, acid extracts of the tissue were immunoprecipitated with either an NH2-terminal ACTH antiserum or a beta-endorphin antiserum and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. After a 24 hr steady label in medium containing [3H]tyrosine, multiple molecular weight forms of beta-endorphin-related and NH2-terminal ACTH-related radioactivity were detected. The major peak of beta-endorphin-related radioactivity co-migrated with synthetic beta-endorphin(1-31); minor peaks of beta LPH-sized material and precursor-sized material were also detected. The major peak of NH2-terminal ACTH-related material co-migrated with synthetic alpha MSH; in addition, smaller amounts of material designated ACTH biosynthetic intermediate 1, ACTH biosynthetic intermediate 2, and precursor-sized material were detected. Sequential immunoprecipitation experiments revealed that the precursor-sized material had antigenic determinants for both alpha MSH and beta-endorphin. Pulse/chase experiments established that this material is the common precursor for alpha MSH and beta-endorphin. Based on gel filtration chromatography in 6 M guanidine HCl, the molecular weights of these various peptides are: common precursor, 23,300 daltons; ACTH biosynthetic intermediate 1, 12,200 daltons; ACTH biosynthetic intermediate 2, 4,200 daltons; alpha MSH, 1,500 daltons; beta LPH, 8000 daltons; beta-endorphin, 3,400 daltons. None of the peptides precipitated with either antiserum incorporated [3H]glucosamine; thus glycosylation does not appear to be involved in this biosynthetic pathway in the lizard. The results of the kinetic experiments and molecular weight determinations indicate that the major biosynthetic pathway involves the following events: common precursor is first cleaved to yield ACTH biosynthetic intermediate 1 plus beta LPH; subsequently, beta LPH is cleaved to produce beta-endorphin; ACTH biosynthetic intermediate 1 is cleaved to produce ACTH biosynthetic intermediate 2 which is subsequently cleaved to produce alpha MSH. The pulse/chase experiments indicate minor pathways exist for cleaving beta-endorphin directly from the common precursor or via a high molecular weight form intermediate in size between the common precursor and beta LPH.

Adrenocorticotropic Hormone↗

PubMed2006

Genetic diseases of sphingolipid metabolism: pathological mechanisms and therapeutic options.

Although diseases in the pathway of sphingolipid degradation have been known for decades, the first disease in the biosynthetic pathway was only reported in 2004, when a form of infantile-onset symptomatic epilepsy was described as a genetic defect in GM3 synthase. Presumably other diseases in the sphingolipid biosynthetic pathway will yet be discovered, although many may remain undetected due to their putative lethal phenotypes. In contrast, diseases are known for essentially every step in the pathway of SL degradation, caused by the defective activity of one or other of the lysosomal hydrolases in this pathway. Despite the fact that some of these storage disorders were first discovered in the 19th century, the cellular and biochemical events that cause pathology are still poorly delineated. In this review, we focus on recent advances in our understanding of how defects in the pathways of sphingolipid metabolism may lead to pathology. In addition, we discuss currently-available and emerging therapeutic options.

Animals↗

PubMed2002

Phospholipase C inhibitors and prostaglandins differentially regulate phosphatidylcholine synthesis in rat renal papilla. Evidence of compartmental regulation of CTP:phosphocholine cytidylyltransferase and CDP-choline:1,2-diacylglycerol cholinephosphotransferase.

Phosphatidylcholine (PC) is the most abundant phospholipid in mammalian cell membranes. Several lines of evidence support that PC homeostasis is preserved by the equilibrium between PC biosynthetic enzymes and phospholipases catabolic activities. We have previously shown that papillary synthesis of PC depends on prostaglandins (PGs) that modulate biosynthetic enzymes. In papillary tissue, under bradikynin stimulus, arachidonic acid (AA) mobilization (the substrate for PG synthesis) requires a previous phospholipase C (PLC) activation. Thus, in the present work, we study the possible involvement of PLC in PC biosynthesis and its relationship with PG biosynthetic pathway on the maintenance of phospholipid renewal in papillary membranes; we also evaluated the relevance of CDP-choline pathway enzymes compartmentalization. To this end, neomycin, U-73122 and dibutiryl cyclic AMP, reported as PLC inhibitors, were used to study PC synthesis in rat renal papilla. All the PLC inhibitors assayed impaired PC synthesis. PG synthesis was also blocked by PLC inhibitors without affecting cyclooxygenase activity, indicating a metabolic connection between both pathways. However, we found that PC biosynthesis decrease in the presence of PLC inhibitors was not a consequence of PG decreased synthesis, suggesting that basal PLC activity and PGs exert their effect on different targets of PC biosynthetic pathway. The study of PC biosynthetic enzymes showed that PLC inhibitors affect CTP:phosphocholine cytidylyltransferase (CCT) activity while PGD(2) operates on CDP-choline:1,2-diacylglycerol cholinephosphotransferase (CPT), both activities associated to papillary enriched-nuclei fraction. The present results suggest that renal papillary PC synthesis is a highly regulated process under basal conditions. Such regulation might occur at least at two different levels of the CDP-choline pathway: on the one hand, PLC operates on CCT activity; on the other, while PGs regulate CPT activity.

Animals↗

PubMed1985

A model for the origin of photosynthesis--III. The ultraviolet photochemistry of uroporphyrinogen.

The photochemical ramifications of the high ultraviolet flux on the primordial earth prior to the formation of the ozone layer have been considered in a study of the ultraviolet photochemistry of uroporphyrinogen (urohexahydroporphyrin), a colorless compound which absorbs strongly at wavelengths less than 220 nanometers. Urohexahydroporphyrin was investigated since it is the first macrocycle formed on the biosynthetic pathway of chlorophyll and can be used to test the hypothesis that the biosynthetic pathway to chlorophyll recapitulates the evolutionary history of photosynthesis. When urohexahydroporphyrin is illuminated in aqueous anaerobic solution, hydrogen gas is produced. More hydrogen gas is produced in the presence of a colloidal platinum catalyst. The products of the photooxidation of urohexahydroporphyrin are urotetrahydroporphyrin (uroporphomethene) and uroporphyrin. This research shows how the oxidation of uroporphyrinogen to uroporphyrin, the first biogenetic porphyrin, could have occurred anaerobically and abiotically on the primordial earth.

Atmosphere↗

PubMed2006

Directed biosynthesis of alkaloid analogs in the medicinal plant Catharanthus roseus.

Terpene indole alkaloids are plant natural products with diverse structures and biological activities. A highly branched biosynthetic pathway is responsible for the production of approximately 130 different alkaloids in Madagascar periwinkle (C. roseus) from a common biosynthetic intermediate derived from tryptamine. Although numerous biosynthetic pathways can incorporate unnatural starting materials to yield novel natural products, it was not clear how efficiently the complex, eukaryotic TIA pathway could utilize unnatural substrates to make new alkaloids. This work demonstrates that the TIA biosynthetic machinery can be used to produce novel alkaloid structures and also highlights the potential of this pathway for future metabolic engineering efforts.

Alkaloids↗

PubMed2004

Evolution of vitamin B6 (pyridoxine) metabolism by gain and loss of genes.

Vitamin B(6) (VB6) functions as a cofactor of many diverse enzymes in amino acid metabolism. Three metabolic pathways for pyridoxal 5'-phosphate (PLP; the active form of VB6) are known: the de novo pathway, the salvage pathway, and the fungal type pathway. Most unicellular organisms and plants biosynthesize VB6 using one or two of these three biosynthetic pathways. However, animals such as insects and mammals do not possess any of the pathways and, thus, need to intake VB6 in their diet to survive. It is conceivable that breakdowns of these pathways occurred in the evolutionary lineages of insects and mammals, and one of the major reasons for this would be the loss of pertinent genes. We studied the evolution of VB6 biosynthesis from the view of the gain and loss of 10 pertinent genes in 122 species whose genome sequences were completely determined. The results revealed that each gene in the pathways was lost more than once in the entire evolutionary lineages of the 122 species. We also found the following three points regarding the evolution of PLP biosynthesis: (1) the breakdown of the PLP biosynthetic pathways occurred independently at least three times in animal lineages, (2) the de novo pathway was formed by the generation of pdxB in gamma-proteobacteria, and (3) the order of the gene loss in VB6 metabolism was conserved among different evolutionary lineages. These results suggest that the evolution of VB6 metabolism was subject to gains and frequent losses of related genes in the 122 species examined. This dynamic nature of the evolutionary changes must have been responsible for the breakdowns of the pathways, resulting in profound differentiation of heterotrophy among the species.

Animals↗

PubMed2006

Biosynthesis of heme in mammals.

Most iron in mammalian systems is routed to mitochondria to serve as a substrate for ferrochelatase. Ferrochelatase inserts iron into protoporphyrin IX to form heme which is incorporated into hemoglobin and cytochromes, the dominant hemoproteins in mammals. Tissue-specific regulatory features characterize the heme biosynthetic pathway. In erythroid cells, regulation is mediated by erythroid-specific transcription factors and the availability of iron as Fe/S clusters. In non-erythroid cells the pathway is regulated by heme-mediated feedback inhibition. All of the enzymes in the heme biosynthetic pathway have been crystallized and the crystal structures have permitted detailed analyses of enzyme mechanisms. All of the genes encoding the heme biosynthetic enzymes have been cloned and mutations of these genes are responsible for a group of human disorders designated the porphyrias and for X-linked sideroblastic anemia. The biochemistry, structural biology and the mechanisms of tissue-specific regulation are presented in this review along with the key features of the porphyric disorders.

Animals↗

PubMed1997

Relationships between phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin metabolism in cultured oligodendrocytes.

In most cell types the major pathway of sphingomyelin synthesis is the direct transfer of the phosphocholine head group from phosphatidylcholine to ceramide catalyzed by the enzyme L-acylsphingosine:phosphatidylcholine phosphocholinetransferase (SM synthase; EC 2.7.8.-). Although this pathway has been demonstrated in brain tissue, its quantitative importance has been questioned. An alternative biosynthetic pathway for sphingomyelin synthesis in brain tissue has been proposed, viz., the direct transfer of phosphoethanolamine from phosphatidylethanolamine to ceramide, followed by methylation of the ethanolamine moiety to a choline group. We have evaluated various possible biosynthetic pathways of sphingomyelin synthesis in rat spinal cord oligodendrocytes, the myelin-forming cells of the CNS, by labeling cells in culture with radiolabeled choline, ethanolamine, or serine. Our results indicate that, in oligodendrocytes, most of the phosphocholine for the biosynthesis of sphingomyelin is provided by phosphatidylcholine, which is predominantly derived from de novo synthesis. No evidence was found for the operation of the alternative pathway via ceramide-phosphoethanolamine. Furthermore, our results indicate that a small pool of phosphatidylcholine is provided by methylation of phosphatidylethanolamine, which in turn is formed preferentially by decarboxylation of phosphatidylserine.

Animals↗

PubMed2026

Complete biosynthesis of the anticancer cephalotaxinone and homoerythratine.

Cephalotaxine-type and homoerythrina-type alkaloids are structurally unique and biologically important natural products isolated from endangered species that belong to the genus Cephalotaxus. Among them, homoharringtonine (HHT [1]) is a marketed drug used to treat leukemia. However, the scalable production of HHT is significantly hindered by limited natural resources. Despite intensive investigation over half a century, the complete biosynthetic pathways of these alkaloids remain unknown. Here, we applied a comprehensive multi-omics analysis and used a set of chemically synthesized standard compounds to identify the missing enzymes required for the biosynthesis of cephalotaxinone and homoerythratine. We also uncovered a rare case of divergent oxidation catalyzed by two highly homologous cytochrome P450 enzymes, CfCYP2 and CfCYP3, in the biosynthesis of two structurally distinct alkaloids. We further identified the key residues that significantly affect the divergent oxidation outcomes and ultimately reconstituted the complete biosynthetic pathways for producing these two alkaloids in N. benthamiana.

Cephalotaxus↗

PubMed1998

Biosynthesis of triacylglycerols containing ricinoleate in castor microsomes using 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine as the substrate of oleoyl-12-hydroxylase.

We have examined the biosynthetic pathway of triacylglycerols containing ricinoleate to determine the steps in the pathway that lead to the high levels of ricinoleate incorporation in castor oil. The biosynthetic pathway was studied by analysis of products resulting from castor microsomal incubation of 1-palmitoyl-2-[14C]oleoyl-sn-glycero-3-phosphocholine, the substrate of oleoyl-12-hydroxylase, using high-performance liquid chromatography, gas chromatography, mass spectrometry, and/or thin-layer chromatography. In addition to formation of the immediate and major metabolite, 1-palmitoyl-2-[14C]ricinoleoyl-sn-glycero-3-phosphocholine, 14C-labeled 2-linoleoyl-phosphatidylcholine (PC), and 14C-labeled phosphatidylethanolamine were also identified as the metabolites. In addition, the four triacylglycerols that constitute castor oil, triricinolein, 1,2-diricinoleoyl-3-oleoyl-sn-glycerol, 1,2-diricinoleoyl-3-linoleoyl-sn-glycerol, 1,2-diricinoleoyl-3-linolenoyl-sn-glycerol, were also identified as labeled metabolites in the incubation along with labeled fatty acids: ricinoleate, oleate, and linoleate. The conversion of PC to free fatty acids by phospholipase A2 strongly favored ricinoleate among the fatty acids on the sn-2 position of PC. A major metabolite, 1-palmitoyl-2-oleoyl-sn-glycerol, was identified as the phospholipase C hydrolyte of the substrate; however, its conversion to triacylglycerols was blocked. In the separate incubations of 2-[14C]ricinoleoyl-PC and [14C]ricinoleate plus CoA, the metabolites were free ricinoleate and the same triacylglycerols that result from incubation with 2-oleoyl-PC. Our results demonstrate the proposed pathway: 2-oleoyl-PC-->2-ricinoleoyl-PC-->ricinoleate-->triacylglycerols. The first two steps as well as the step of diacylglycerol acyltransferase show preference for producing ricinoleate and incorporating it in triacylglycerols over oleate and linoleate. Thus, the productions of these triacylglycerols in this relatively short incubation (30 min), as well as the availability of 2-oleoyl-PC in vivo, reflect the in vivo drive to produce triricinolein in castor bean.

Ricinus communis↗

PubMed2006

The bifunctional glyceryl transferase/phosphatase OzmB belonging to the HAD superfamily that diverts 1,3-bisphosphoglycerate into polyketide biosynthesis.

The HAD superfamily protein OzmB from the oxazolomycin biosynthetic pathway is shown to divert the primary metabolite 1,3-diphosphoglycerate into the polyketide biosynthetic pathway as glycerate via loading of a carrier protein. Each of the steps-activation of d-3-phosphoglycerate, dephosphorylation while attached to a cysteine on OzmB, and subsequent transfer of glycerate to the phosphopantetheinyl thiol of an acyl carrier protein-was monitored by nanospray Fourier transform mass spectrometry. This activation of phosphoglycerate represents a general mechanism of diverting glycolytic metabolites into glyceryl-derived polyketides.

Amino Acid Sequence↗

PubMed2001

The role of the yeast plasma membrane SPS nutrient sensor in the metabolic response to extracellular amino acids.

In response to discrete environmental cues, Saccharomyces cerevisiae cells adjust patterns of gene expression and protein activity to optimize metabolism. Nutrient-sensing systems situated in the plasma membrane (PM) of yeast have only recently been discovered. Ssy1p is one of three identified components of the Ssy1p-Ptr3p-Ssy5 (SPS) sensor of extracellular amino acids. SPS sensor-initiated signals are known to modulate the expression of a number of amino acid and peptide transporter genes (i.e. AGP1, BAP2, BAP3, DIP5, GAP1, GNP1, TAT1, TAT2 and PTR2) and arginase (CAR1). To obtain a better understanding of how cells adjust metabolism in response to extracellular amino acids in the environment and to assess the consequences of loss of amino acid sensor function, we investigated the effects of leucine addition to wild-type and ssy1 null mutant cells using genome-wide transcription profile analysis. Our results indicate that the previously identified genes represent only a subset of the full spectrum of Ssy1p-dependent genes. The expression of several genes encoding enzymes in amino acid biosynthetic pathways, including the branched-chain, lysine and arginine, and the sulphur amino acid biosynthetic pathways, are modulated by Ssy1p. Additionally, the proper transcription of several nitrogen-regulated genes, including NIL1 and DAL80, encoding well-studied GATA transcription factors, is dependent upon Ssy1p. Finally, several genes were identified that require Ssy1p for wild-type expression independently of amino acid addition. These findings demonstrate that yeast cells require the SPS amino acid sensor component, Ssy1p, to adjust diverse cellular metabolic processes properly.

Amino Acids↗

PubMed2026

Integrated Metabolomic and Transcriptomic Analysis Reveals Tissue-Specific Secondary Metabolic Differentiation and Indole Alkaloid Accumulation in Evodia rutaecarpa.

Evodia rutaecarpa is a valuable medicinal plant, yet its non-medicinal tissues remain largely underexplored. Here, we integrated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based widely targeted metabolomics and RNA sequencing (RNA-seq) transcriptomics to systematically profile the metabolic and transcriptional landscapes of roots, stems, leaves, and flowers of Evodia rutaecarpa (Juss.) Benth. Our aim was to characterize tissue-specific metabolic differentiation and its underlying transcriptional regulatory mechanisms. Metabolomic analysis, employing principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) with robust model parameters (R2Y > 0.9, Q2 > 0.5), identified 3090 differential metabolite features (variable importance in projection, VIP > 1.0; p < 0.05) across the four tissues, which exhibited distinct tissue-specific clustering patterns. Integrated Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and weighted gene co-expression network analysis (WGCNA) revealed that roots specifically accumulated quinolone alkaloids and flavonoid glycosides, accompanied by the coordinated upregulation of genes involved in flavonoid and phenylpropanoid biosynthetic pathways. In contrast, stems, leaves, and flowers were enriched in indole alkaloids (evodiamine and rutaecarpine) and volatile oil precursors, with concurrent upregulation of genes involved in tryptophan metabolism and indole alkaloid biosynthesis (e.g., tryptophan decarboxylase, TDC; s N-methyltransferase, NMT). Notably, leaves and flowers displayed particularly high accumulation levels of these bioactive alkaloids, suggesting their potential as alternative sources for industrial and pharmaceutical applications. WGCNA further identified multiple transcription factors and structural gene modules tightly correlated with evodiamine accumulation, offering promising candidate regulators for future biosynthetic pathway engineering. Collectively, this multi-omics integration study systematically elucidates the tissue-partitioned secondary metabolism of Evodia rutaecarpa (Juss.) Benth. and provides a solid scientific foundation for full-plant resource utilization, targeted development of non-medicinal tissues, and future metabolic engineering of indole alkaloid production.

Evodia rutaecarpa↗