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In this overview, naturally occurring resorcylic lactones biosynthetically derived from alternariol and almost exclusively produced by fungi, are discussed with view on their isolation, structure, biological activities, biosynthesis, and total syntheses. This class of compounds consists until now of 127 naturally occurring compounds, with very divers structural motifs. Although only a handful of these toxins (i.e., alternariol and its 9-O-methyl ether, altenusin, dehydroaltenusin, altertenuol, and altenuene) were frequently found and isolated as fungal contaminants in food and feed and have been investigated in significant detail, further metabolites, which were much more rarely found as natural products, similarly show interesting biological activities.
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Plant growth-promoting microorganisms (PGPMs), such as Pantoea sp. YSD J2, promote plant development and stress resistance, while their role in flavonoids accumulation still needs to be further understood. To investigate the complex flavonoid biosynthesis pathway of Cyperus esculentus L. var. sativus (tigernut), we compared Pantoea sp. YSD J2 inoculation (YSD J2) and water inoculation (CK) groups. YSD J2 significantly elevated the content of indole-3-acetic acid (IAA) and orientin. Furthermore, when analyzing flavonoid metabolome, YSD J2 caused increased levels of uralenol, petunidin-3-O-glucoside-5-O-arabinoside, luteolin-7-O-glucuronide-(2 â 1)-glucuronide, kaempferol-3-O-neohesperidoside, cyanidin-3-O-(2â³-O-glucosyl)glucoside, kaempferol-3-O-glucuronide-7-O-glucoside, quercetin-3-O-glucoside, luteolin-7-O-glucuronide-(2 â 1)-(2â³-sinapoyl)glucuronide, and quercetin-4'-O-glucoside, which further enhanced antioxidant activity. We then performed RNA-seq and LC-MS/MS, aiming to validate key genes and related flavonoid metabolites under YSD J2 inoculation, and rebuild the gene-metabolites regulatory subnetworks. Furthermore, the expression patterns of the trans cinnamate 4-monooxygenase (CYP73A), flavonol-3-O-L-rhamnoside-7-O-glucosyltransferase (UGT73C6), shikimate O-hydroxycinnamoyltransferase (HCT), chalcone isomerase (CHI), flavonol synthase (FLS), and anthocyanidin synthase (ANS) genes were confirmed by qRT-PCR. Additionally, 4 transcription factors (TF) (especially bHLH34, Cluster-37505.3) under YSD J2 inoculation are also engaged in regulating flavonoid accumulation. Moreover, the current work sheds new light on studying the regulatory effect of Pantoea sp. YSD J2 on tigernut development and flavonoid biosynthesis.
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Houttuynia cordata Thunb., also known as Yuxingcao in Chinese, is a perennial herb in the Saururaceae family. It is highly regarded for its medicinal properties, particularly in treating respiratory infections and inflammatory conditions, as well as boosting the human immune system. However, the lack of genomic information has hindered research on the functional genomics and potential improvements of H. cordata. In this study, we present the assembly of a near-complete genome of H. cordata and investigate the biosynthesis pathway of flavonoids, specifically quercetin, using genomics, transcriptomics, and metabolomics analysis. The genome of H. cordata diverged from Saururus chinensis around 33.4 million years ago and consists of 2.24 Gb with 76 chromosomes (4n = 76), which underwent three whole-genome duplication (WGD) events. These WGDs played a crucial role in shaping H. cordata's genome and influencing gene families associated with its medicinal properties. Through metabolomics and transcriptomics analysis, we identified key genes involved in the ß-oxidation process for houttuynin biosynthesis, one of the volatile oils responsible for its fishy-smell. Additionally, utilizing the reference genome, we effectively identified genes involved in flavonoid biosynthesis, particularly quercetin metabolism in H. cordata. This discovery has paramount implications for understanding the regulatory mechanisms of active pharmaceutical ingredient production in traditional Chinese medicine. Overall, the high-quality genome of H. cordata serves as a crucial resource for future functional genomics research and provides a solid foundation for genetic improvement of H. cordata for the benefit of human health.
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The modern nanomedicine incorporates the multimodal treatments into a single formulation, offering innovative cancer therapy options. Nanosheets function as carriers, altering the solubility, biodistribution, and effectiveness of medicinal compounds, resulting in more efficient cancer treatments and reduced side effects. The non-toxic nature of fluorinated graphene oxide (FGO) nanosheets and their potential applications in medication delivery, medical diagnostics, and biomedicine distinguish them from others. Leveraging the unique properties of Lissachatina fulica snail mucus (LfSM), FGO nanosheets were developed to reveal the novel characteristics. Consequently, LfSM was utilized to create non-toxic, environmentally friendly, and long-lasting FGO nanosheets. Ultraviolet-visible (UV-vis) spectroscopy revealed a prominent absorbance peak at 235 nm. The characterization of the synthesized FGO nanosheets involved X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HR-TEM), and atomic force microscopy (AFM) analyses. The antimicrobial activity data demonstrated a broad spectrum of antibacterial effects against Escherichia coli, Bacillus subtilis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The cytotoxicity efficacy of LfSM-FGO nanosheets against pancreatic cancer cell line (PANC1) showed promising results at low concentrations. The study suggests that FGO nanosheets made from LfSM could serve as alternate factors for in biomedical applications in the future.
Subject(s)
Graphite , Nanostructures , Snails , Graphite/chemistry , Graphite/pharmacology , Animals , Snails/chemistry , Humans , Nanostructures/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Microbial Sensitivity Tests , Mucus/chemistry , Mucus/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Halogenation , Cell Survival/drug effects , Escherichia coli/drug effects , Cell Line, Tumor , Particle SizeABSTRACT
Among nearly a hundred known bioluminescent systems, only about a dozen have been studied to some extent, and the structures of only a few luciferins have been established. Moreover, the biosynthesis pathway is known only for two of them - the fungal and bacterial ones. Marine polychaetes of the Odontosyllis genus possess bright bioluminescence. The structures of its bioluminescence system key components were recently elucidated, and a possible pathway of the luciferin biosynthesis was proposed. Here we report the transaminase enzyme from Odontosyllis undecimdonta, the first potential participant of the cascade. We demonstrate that the discovered ferment catalyzes the transamination of the cys2DOPA, one of the potential luciferin biosynthetic precursors. The results of the experiments support the hypothesis that the discovered enzyme might be the part of the Odontosyllis luciferin biosynthesis pathway.
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Trichomes are specialized epidermal outgrowths covering the aerial parts of most terrestrial plants. There is a large species variability in occurrence of different types of trichomes such that the molecular regulatory mechanism underlying the formation and the biological function of trichomes in most plant species remain unexplored. Here, we used Chrysanthemum morifolium as a model plant to explore the regulatory network in trichome formation and terpenoid synthesis and unravel the physical and chemical roles of trichomes in constitutive defense against herbivore feeding. By analyzing the trichome-related genes from transcriptome database of the trichomes-removed leaves and intact leaves, we identified CmMYC2 to positively regulate both development of T-shaped and glandular trichomes as well as the content of terpenoids stored in glandular trichomes. Furthermore, we found that the role of CmMYC2 in trichome formation and terpene synthesis was mediated by interaction with CmMYBML1. Our results reveal a sophisticated molecular mechanism wherein the CmMYC2-CmMYBML1 feedback inhibition loop regulates the formation of trichomes (non-glandular and glandular) and terpene biosynthesis, collectively contributing to the enhanced resistance to Spodoptera litura larvae feeding. Our findings provide new insights into the novel regulatory network by which the plant synchronously regulates trichome density for the physical and chemical defense against herbivory.
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The only known pathway for biosynthesis of the polyamine norspermidine starts from aspartate ß-semialdehyde to form the diamine 1,3-diaminopropane, which is then converted to norspermidine via a carboxynorspermidine intermediate. This pathway is found primarily in the Vibrionales order of the γ-Proteobacteria. However, norspermidine is also found in other species of bacteria and archaea, and in diverse single-celled eukaryotes, chlorophyte algae and plants that do not encode the known norspermidine biosynthetic pathway. We reasoned that products of polyamine catabolism could be an alternative route to norspermidine production. 1,3-diaminopropane is formed from terminal catabolism of spermine and spermidine, and norspermidine can be formed from catabolism of thermospermine. We found that the single-celled chlorophyte alga Chlamydomonas reinhardtii thermospermine synthase (CrACL5) did not aminopropylate exogenously-derived 1,3-diaminopropane efficiently when expressed in E. coli. In contrast, it completely converted all E. coli native spermidine to thermospermine. Co-expression in E. coli of the polyamine oxidase 5 from lycophyte plant Selaginella lepidophylla (SelPAO5), together with the CrACL5 thermospermine synthase, converted almost all thermospermine to norspermidine. Although CrACL5 was efficient at aminopropylating norspermidine to form tetraamine norspermine, SelPAO5 oxidizes norspermine back to norspermidine, with the balance of flux being inclined fully to norspermine oxidation. The steady-state polyamine content of E. coli co-expressing thermospermine synthase CrACL5 and polyamine oxidase SelPAO5 was an almost total replacement of spermidine by norspermidine. We have recapitulated a potential hybrid biosynthetic-catabolic pathway for norspermidine production in E. coli, which could explain norspermidine accumulation in species that do not encode the known aspartate ß-semialdehyde-dependent pathway.
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Potato tubers accumulate substantial quantities of starch, which serves as their primary energy reserve. As the predominant component of potato tubers, starch strongly influences tuber yield, processing quality, and nutritional attributes. Potato starch is distinguished from other food starches by its unique granule morphology and compositional attributes. It possesses large, oval granules with amylose content ranging from 20 to 33 % and high phosphorus levels, which collectively determine the unique physicochemical characteristics. These physicochemical properties direct the utility of potato starch across diverse food and industrial applications. This review synthesizes current knowledge on the molecular factors controlling potato starch biosynthesis and structure-function relationships. Key topics covered are starch granule morphology, the roles and regulation of major biosynthetic enzymes, transcriptional and hormonal control, genetic engineering strategies, and opportunities to tailor starch functionality. Elucidating the contributions of different enzymes in starch biosynthesis has enabled targeted modification of potato starch composition and properties. However, realizing the full potential of this knowledge faces challenges in optimizing starch quality without compromising plant vigor and yield. Overall, integrating multi-omics datasets with advanced genetic and metabolic engineering tools can facilitate the development of elite cultivars with enhanced starch yield and tailored functionalities.
Subject(s)
Metabolic Engineering , Solanum tuberosum , Starch , Solanum tuberosum/metabolism , Solanum tuberosum/genetics , Solanum tuberosum/chemistry , Starch/chemistry , Starch/metabolism , Starch/biosynthesis , Metabolic Engineering/methods , Plant Tubers/metabolism , Plant Tubers/chemistry , Amylose/biosynthesis , Amylose/metabolism , Amylose/chemistry , Gene Expression Regulation, Plant , Plant Proteins/metabolism , Plant Proteins/geneticsABSTRACT
The rapid expansion of multi-omics data has transformed biological research, offering unprecedented opportunities to explore complex genomic relationships across diverse organisms. However, the vast volume and heterogeneity of these datasets presents significant challenges for analyses. Here we introduce SocialGene, a comprehensive software suite designed to collect, analyze, and organize multi-omics data into structured knowledge graphs, with the ability to handle small projects to repository-scale analyses. Originally developed to enhance genome mining for natural product drug discovery, SocialGene has been effective across various applications, including functional genomics, evolutionary studies, and systems biology. SocialGene's concerted Python and Nextflow libraries streamline data ingestion, manipulation, aggregation, and analysis, culminating in a custom Neo4j database. The software not only facilitates the exploration of genomic synteny but also provides a foundational knowledge graph supporting the integration of additional diverse datasets and the development of advanced search engines and analyses. This manuscript introduces some of SocialGene's capabilities through brief case studies including targeted genome mining for drug discovery, accelerated searches for similar and distantly related biosynthetic gene clusters in biobank-available organisms, integration of chemical and analytical data, and more. SocialGene is free, open-source, MIT-licensed, designed for adaptability and extension, and available from github.com/socialgene.
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Starch is a primary source of food energy for human beings. Its chain-length distribution (CLD) is a major structural feature influencing physiologically-important properties, such as digestibility and palatability, of starch-containing foods. Diabetes, which is of epidemic proportions in many countries, is related to the rate of starch digestion in foods. Isoforms of three biosynthesis enzymes, starch synthase, starch branching enzymes and debranching enzymes, control the CLDs of starch, which can be measured by methods such as size-exclusion chromatography and fluorophore-assisted carbohydrate electrophoresis. Fitting observed CLDs to biosynthesis-based models based on the ratios of the activities of those isoforms yields biosynthesis-related parameters describing CLD features. This review examines CLD measurement, fitting CLDs to models, relations between CLDs, the occurrence and management of diabetes, and how plant breeders can develop varieties to optimize digestibility and palatability together, to develop starch-based foods with both a lower risk of diabetes and acceptable taste.
Subject(s)
Diabetes Mellitus , Starch , Starch/chemistry , Starch/metabolism , Humans , Diabetes Mellitus/metabolism , Starch Synthase/metabolism , Digestion , Molecular Structure , AnimalsABSTRACT
Lasso peptides are a large and sequence-diverse class of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products characterized by their slip knot-like shape. These unique, highly stable peptides are produced by bacteria for various purposes. Their stability and sequence diversity make them a potentially useful scaffold for biomedically relevant folded peptides. However, many questions remain about lasso peptide biosynthesis, ecological function, and diversification potential for biomedical and agricultural applications. This review discusses new insights and open questions about lasso peptide biosynthesis and biological function. The role that genome mining has played in the development of new methodologies for discovering and diversifying lasso peptides is also discussed.
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Objective: The aim of this study is to comprehensively investigate the temporal dynamics of faecal gut microbiota and metabonomics in early postnatal with a focus on very low or extremely low birth weight (VLBW/ELBW) infants. Methods: We collected faecal samples from 157 VLBW/ELBW infants at three time points: days 1, 14, and 28 in a prospective cohort study. The faecal microbial diversity, abundance, composition, and metabolomic analyses were determined using 16S rRNA sequencing and liquid chromatography tandem mass spectrometry (LC-MS/MS). Microbiome functional analyses were conducted utilizing PICRUSt2. The ecological association networks were employed to investigate the interactions between gut microbiota and identify the core genus within 28 days of birth, as well as to unveil correlations between taxa and metabolites. Result: (1) The alpha diversity of gut microbiota significantly decreased from D1 to D28, accompanied by an interrupted trajectory lacking obligate anaerobes. At the phylum level, the 16S RNA sequencing results showed an increase in Proteobacteria and a decrease in Firmicutes and Bacteroidota from D1 to D28. At the genus level, there was a decrease in the relative abundance of Staphylococcus, Acinetobacter and Ureaplasma, with Klebsiella and Enterococcus emerging as the most abundant genera. (2) The analysis revealed a total of 561 metabolic markers that exhibited significant and distinct alterations between D1 and D14. (3) Ecological association networks revealed that the gut microbiota in D1 exhibited a significantly higher degree of microbial interactions compared to those in D14 and D28. Additionally, Enterococcus, Klebsiella, and Enterobacter were major contributors to the co-occurring network at these three time points. (4) Steroid hormone biosynthesis, including tetrahydrocortisone, androsterone glucuronide, androstenedione and etiocholanolone glucuronide, decreased within 28 days after birth. Conclusion: We have successfully demonstrated a significant dysbiosis in the gut microbiota and a subsequent decrease in its diversity within 4 weeks postpartum in VLBW/ELBW infants. Monitoring the gut microbiota of VLBW/ELBW infants and promptly rectifying dysbiosis in the early stages may represent a potential therapeutic strategy.
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Coumarins, derived from the phenylpropanoid pathway, represent one of the primary metabolites found in angiosperms. The alignment of the tetrahydropyran (THP) and tetrahydrofuran (THF) rings with the lactone structure results in the formation of at least four types of complex coumarins. However, the mechanisms underlying the structural diversity of coumarin remain poorly understood. Here, we report the chromosome-level genome assembly of Notopterygium incisum, spanning 1.64 Gb, with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding genes. Additionally, we identified the key enzymes responsible for shaping the structural diversity of coumarins, including two p-coumaroyl CoA 2'-hydroxylases crucial for simple coumarins basic skeleton architecture, two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis, and five CYP736 cyclases involved in THP and THF ring formation. Notably, two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first time. Evolutionary analysis implies that tandem and ectopic duplications of the CYP736 subfamily, specifically arising in the Apiaceae, contributed to the structural diversity of coumarins in N. incisum. Conclusively, this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.
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Biosynthesis and biodegradation of microorganisms critically underpin the development of biotechnology, new drugs and therapies, and environmental remediation. However, most uncultured microbial species along with their metabolic capacities in extreme environments, remain obscured. Here we unravel the metabolic potential of microbial dark matters (MDMs) in four deep-inland hypersaline lakes in Xinjiang, China. Utilizing metagenomic binning, we uncovered a rich diversity of 3030 metagenome-assembled genomes (MAGs) across 82 phyla, revealing a substantial portion, 2363 MAGs, as previously unclassified at the genus level. These unknown MAGs displayed unique distribution patterns across different lakes, indicating a strong correlation with varied physicochemical conditions. Our analysis revealed an extensive array of 9635 biosynthesis gene clusters (BGCs), with a remarkable 9403 being novel, suggesting untapped biotechnological potential. Notably, some MAGs from potentially new phyla exhibited a high density of these BGCs. Beyond biosynthesis, our study also identified novel biodegradation pathways, including dehalogenation, anaerobic ammonium oxidation (Anammox), and degradation of polycyclic aromatic hydrocarbons (PAHs) and plastics, in previously unknown microbial clades. These findings significantly enrich our understanding of biosynthesis and biodegradation processes and open new avenues for biotechnological innovation, emphasizing the untapped potential of microbial diversity in hypersaline environments.
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The synthesis of fatty acids plays a critical role in shaping milk production characteristics in dairy cattle. Thus, identifying effective haplotypes within the fatty acid metabolism pathway will provide novel and robust insights into the genetics of dairy cattle. This study aimed to comprehensively examine the individual and combined impacts of fundamental genes within the fatty acid metabolic process pathway in Jersey cows. A comprehensive phenotypic dataset was compiled, considering milk production traits, to summarize a cow's productivity across three lactations. Genotyping was conducted through PCR-RFLP and Sanger sequencing, while the association between genotype and phenotype was quantified using linear mixed models. Moderate biodiversity and abundant variation suitable for haplotype analysis were observed across all examined markers. The individual effects of the FABP3, LTF and ANXA9 genes significantly influenced both milk yield and milk fat production. Additionally, this study reveals novel two-way interactions between genes in the fatty acid metabolism pathway that directly affect milk fat properties. Notably, we identified that the GGAAGG haplotype in FABP3×LTF×ANXA9 interaction may be a robust genetic marker concerning both milk fat yield and percentage. Consequently, the genotype combinations highlighted in this study serve as novel and efficient markers for assessing the fat content in cow's milk.
Subject(s)
Fatty Acids , Lactation , Milk , Animals , Cattle/genetics , Cattle/physiology , Fatty Acids/metabolism , Milk/chemistry , Milk/metabolism , Female , Lactation/genetics , Haplotypes , Genetic Variation , Genotype , Phenotype , Fatty Acid Binding Protein 3/genetics , Fatty Acid Binding Protein 3/metabolism , Annexins/genetics , Annexins/metabolismABSTRACT
In an effort to pursue a green synthesis approach, the biosynthesis of nano-silver (nAg) using plant extracts has garnered significant attention, particularly for its antimicrobial resistance and medical applications, which have been the focus of numerous studies. However, there remains a gap in surface catalytic studies, especially regarding the hydrogenation of 4-nitrophenol. While some studies have addressed catalytic kinetics, thermodynamic aspects have been largely overlooked, leaving the catalytic mechanisms of biosynthesized nAg unclear. In this context, the present work offers a straightforward, eco-friendly, and efficient protocol to obtain nano-silver inspired by Musa paradisiaca L. peel extract. This nAg serves multiple purposes, including antimicrobial resistance and as an eco-catalyst for hydrogenation. Predominantly consisting of zero-valent silver with anisotropic polyhedral shapes, mainly decahedra with an edge length of 50 nm, this nAg demonstrated effective antimicrobial action against both S. aureus and E. coli bacteria. More importantly, both kinetic and thermodynamic studies on the hydrogenation of 4-nitrophenol to 4-aminophenol catalyzed by this bio-inspired nAg revealed that the rate-limiting step is not diffusion-limited. Instead, the adsorbed hydrogen and 4-nitrophenolate react together via electron transfer on the surface of the nAg. The activation energy of 26.24 kJ mol-1 indicates a highly efficient eco-catalyst for such hydrogenation processes.
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The recombinant adeno-associated virus (rAAV) vector is among the most promising viral vectors in gene therapy. However, the limited manufacturing capacity in human embryonic kidney (HEK) cells is a barrier to rAAV commercialization. We investigated the impact of endoplasmic reticulum (ER) protein processing and apoptotic genes on transient rAAV production in HEK293 cells. We selected four candidate genes based on prior transcriptomic studies: XBP1, GADD34 / PPP1R15A, HSPA6, and BCL2. These genes were stably integrated into HEK293 host cells. Traditional triple-plasmid transient transfection was used to assess the vector production capability and the quality of both the overexpressed stable pools and the parental cells. We show that the overexpression of XBP1, HSPA6, and GADD34 increases rAAV productivity by up to 100% and increases specific rAAV productivity by up to 78% in HEK293T cells. Additionally, more prominent improvement associated with ER protein processing gene overexpression was observed when parental cell productivity was high, but no substantial variation was detected under low-producing conditions. We also confirmed genome titer improvement across different serotypes (AAV2 and AAV8) and different cell lines (HEK293T and HEK293); however, the extent of improvement may vary. This study unveiled the importance of ER protein processing pathways in viral particle synthesis, capsid assembly, and vector production. KEY POINTS: ⢠Upregulation of endoplasmic reticulum (ER) protein processing (XBP1, HSPA6, and GADD34) leads to a maximum 100% increase in rAAV productivity and a maximum 78% boost in specific rAAV productivity in HEK293T cells ⢠The enhancement in productivity can be validated across different HEK293 cell lines and can be used for the production of various AAV serotypes, although the extent of the enhancement might vary slightly ⢠The more pronounced improvements linked to overexpressing ER protein processing genes were observed when parental cell productivity was high, with minimal variation noted under low-producing conditions.
Subject(s)
Dependovirus , Endoplasmic Reticulum , Genetic Vectors , X-Box Binding Protein 1 , Humans , HEK293 Cells , Dependovirus/genetics , X-Box Binding Protein 1/genetics , X-Box Binding Protein 1/metabolism , Endoplasmic Reticulum/metabolism , Genetic Vectors/genetics , Gene Expression , Protein Phosphatase 1/genetics , Protein Phosphatase 1/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Capsid/metabolismABSTRACT
Photosynthetic biohybrid systems (PBSs) composed of semiconductor-microbial hybrids provide a novel approach for converting light into chemical energy. However, comprehending the intricate interactions between materials and microbes that lead to PBSs with high apparent quantum yields (AQY) is challenging. Machine learning holds promise in predicting these interactions. To address this issue, this study employs ensemble learning (ESL) based on Random Forest, Gradient Boosting Decision Tree, and eXtreme Gradient Boosting to predict AQY of PBSs utilizing a dataset comprising 15 influential factors. The ESL model demonstrates exceptional accuracy and interpretability (R2 value of 0.927), offering insights into the impact of these factors on AQY while facilitating the selection of efficient semiconductors. Furthermore, this research propose that efficient charge carrier separation and transfer at the bio-abiotic interface are crucial for achieving high AQY levels. This research provides guidance for selecting semiconductors suitable for productive PBSs while elucidating mechanisms underlying their enhanced efficiency.
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BACKGROUND: Walnut is an oilseed tree species and an ecologically important woody tree species that is rich in oil and nutrients. In light of differences in the lipid content, fatty acid composition and key genes expression patterns in different walnut varieties, the key gene regulatory networks for lipid biosynthesis in different varieties of walnuts were intensively investigated. RESULTS: The kernels of two walnut varieties, 'Xilin 3' (X3) and 'Xiangling' (XL) were sampled at 60, 90, and 120 days post-anthesis (DPA) to construct 18 cDNA libraries, and the candidate genes related to oil synthesis were identified via sequencing and expression analysis. A total of 106 differentially expressed genes associated with fatty acid biosynthesis, fatty acid elongation, unsaturated fatty acid biosynthesis, triglyceride assembly, and oil body storage were selected from the transcriptomes. Weighted gene co-expression network analysis (WGCNA), correlation analysis and quantitative validation confirmed the key role of the FAD3 (109002248) gene in lipid synthesis in different varieties. CONCLUSIONS: These results provide valuable resources for future investigations and new insights into genes related to oil accumulation and lipid metabolism in walnut seed kernels. The findings will also aid future molecular studies and ongoing efforts to genetically improve walnut.
Subject(s)
Gene Expression Profiling , Juglans , Seeds , Juglans/genetics , Juglans/metabolism , Juglans/growth & development , Seeds/genetics , Seeds/metabolism , Seeds/growth & development , Transcriptome , Gene Expression Regulation, Plant , Lipids/biosynthesis , Plant Proteins/genetics , Plant Proteins/metabolism , Nuts/genetics , Nuts/growth & development , Nuts/metabolism , Genes, Plant , Lipid Metabolism/genetics , Gene Regulatory NetworksABSTRACT
Inosine 5'-monophosphate dehydrogenase (IMPDH), known as GuaB in bacteria, catalyzes the rate-limiting step in de novo guanine biosynthesis and is conserved from humans to bacteria. We developed a series of potent inhibitors that selectively target GuaB over its human homolog. Here, we show that these GuaB inhibitors are bactericidal, generate phenotypic signatures that are distinct from other antibiotics, and elicit different time-kill kinetics and regulatory responses in two important Gram-negative pathogens: Acinetobacter baumannii and Escherichia coli. Specifically, the GuaB inhibitor G6 rapidly kills A. baumannii but only kills E. coli after 24 h. After exposure to G6, the expression of genes involved in purine biosynthesis and stress responses change in opposite directions while siderophore biosynthesis is downregulated in both species. Our results suggest that different species respond to GuaB inhibition using distinct regulatory programs and possibly explain the different bactericidal kinetics upon GuaB inhibition. The comparison highlights opportunities for developing GuaB inhibitors as novel antibiotics.IMPORTANCEA. baumannii is a priority bacterial pathogen for which development of new antibiotics is urgently needed due to the emergence of multidrug resistance. We recently developed a series of specific inhibitors against GuaB, a bacterial inosine 5'-monophosphate dehydrogenase, and achieved sub-micromolar minimum inhibitory concentrations against A. baumannii. GuaB catalyzes the rate-limiting step of de novo guanine biosynthesis and is highly conserved across bacterial pathogens. This study shows that inhibition of GuaB induced a bacterial morphological profile distinct from that of other classes of antibiotics, highlighting a novel mechanism of action. Moreover, our transcriptomic analysis showed that regulation of de novo purine biosynthesis and stress responses of A. baumannii upon GuaB inhibition differed significantly from that of E. coli.