Acid Biosynthesis Research Articles

Transcriptomics-guided rational engineering in Bacillus licheniformis for enhancing poly-γ-glutamic acid biosynthesis using untreated molasses

The utilization of non-food raw materials for microbial synthesis of poly-γ-glutamic acid (γ-PGA) presents a promising alternative to conventional food-based biosynthesis. However, the complex carbon source and composition of molasses, a prevalent non-food raw material, may impose constraints on its conversion and utilization by microorganisms. This study aimed to enhance the capacity of Bacillus licheniformis to convert untreated molasses into γ-PGA through transcriptomic analysis to guide metabolic modifications. Initial results from the transcriptomic analysis indicated that the strain utilizing molasses exhibited decreased expression of genes associated with substrate utilization (Module 1) and by-product synthesis (Module 2), while upregulating genes related to precursor synthesis (Module 3). Furthermore, we performed a knockout of the acetolactate synthase (AlsS) to reduce the synthesis of metabolic by-products and a knockout of the global regulator (CcpA) to alleviate carbon catabolite repression (CCR) and then promote substrate utilization. Ultimately, following the tandem overexpression of precursor supplying key genes, the titer of γ-PGA reached 48.26 g/L with a productivity of 1.15 g/L/h, using untreated molasses as the sole carbon source, which was 3.12-fold of the starting strain. These findings offer significant insights into the cost-effective synthesis of γ-PGA by bioconversion of untreated molasses during fermentation.

Triphasic Development of the Genetic Code.

The genetic code contains an alphabet of genetically encoded amino acids. The ten Phase 1 amino acids, including Gly, Ala, Ser, Asp, Glu, Val, Leu, Ile, Pro and Thr, were available from the prebiotic environment, whereas the ten Phase 2 amino acids, including Phe, Tyr, Arg, His, Trp, Asn, Gln, Lys, Cys, and Met, became available only later from amino acid biosyntheses. In the archaeon Methanopyrus kandleri, the oldest organism known, the standard alphabet of 20 amino acids was "frozen" and no additional amino acid was encoded in the subsequent 3 Gyrs. Four decades ago, it was discovered that the code was frozen because all the organisms were so well adapted to the standard amino acids that oligogenic barriers, consisting of genes that are thoroughly dependent on the standard code, would cause loss of viability upon the deletion of any one amino acid from the code. Once the reason for the freezing of the code was ascertained, procedures were devised by scientists worldwide to enable the encoding of novel noncanonical amino acids (ncAAs). These encoded Phase 3 ncAAs now surpass the 20 canonical Phase 2 amino acids in the code.

Integrated genomic and functional analysis of Streptomyces sp. UP1A-1 for bacterial wilt control and solanaceae yield increase

Ralstonia solanacearum is one of the most destructive soil-borne pathogen, causing bacterial wilt to the solanaceae vegetables. Streptomyces sp. UP1A-1 isolated from healthy solanaceae rhizosphere soil, exhibited the lowest disease incidence and increased fruit yield of solanaceae vegetables. However, the genomic and functional properties of UP1A-1 are unclear. Therefore, we conducted the present study to elucidate the genomic characteristics of UP1A-1 by whole genome sequencing. The results indicate that the genome of Streptomyces sp. UP1A-1 consists of 8,252,902 bp and contains 72.42 % G + C. We identified the genes that confer plant growth promoting (PGP) function, which include those involved in siderophore production, indole-3-acetic acid biosynthesis, phosphate solubilization, nitrogen metabolism, and potassium metabolism. We also identified several other genes, such as chitinase, peroxidase, superoxide dismutase, catalase, proline biosynthesis, and glucose dehydrogenase, which are believed to be involved in the control of wilt disease. These genes revealed that the strain UP1A-1 has physiologically adapted to varied environmental conditions and could potentially control both abiotic and biotic stresses.

Soil microbial communities and degradation of pesticides in greenhouse effluent through a woodchip bioreactor

Pesticides, including insecticides and fungicides, are major contaminants in the effluent from intensive agricultural systems, such as greenhouses. Because of their constant use and persistence, some pesticides can accumulate in soil and/or run off into adjacent waterways. Microbial communities in soil can degrade some pesticides, and bioreactors with enhanced microbial communities have the potential to facilitate decontamination before the effluent is released into the environment. In this study, we sampled the soil along a gradient from immediately below greenhouses, into, through and below a bioreactor. Multi-analyte pesticide screening was undertaken along with shotgun metagenomic sequencing, to assess microbial community taxonomic profiles and metabolic pathway responses for functional analysis. Two insecticides (imidacloprid and fipronil) and nine fungicides were identified in the soil samples, with a general decrease in most pesticides with increasing distance from the greenhouses. Diversity indexes of taxonomic profiles show changes in the microbial community along the gradient. In particular, microbial communities were significantly different in the bioreactor, with lower Shannon diversity compared to immediately below the greenhouses, in the channels leading into the bioreactor and further downstream. Metabolic pathway analysis revealed significant changes in a wide range of core housekeeping genes such as protein/amino acid synthesis and lipid/fatty acid biosynthesis among the sampling sites. The result demonstrates that the composition and potential functional pathways of the microbial community shifted towards an increased tendency for phytol and contaminant degradation in the bioreactor, facilitated by high organic matter content. This highlights the potential to use enhanced microbial communities within bioreactors to reduce contamination by some pesticides in sediment receiving run-off from greenhouses.

Comparative genomics reveals insights into the potential of Lysinibacillus irui as a plant growth promoter

Members of the genus Lysinibacillus attract attention for their mosquitocidal, bioremediation, and plant growth-promoting abilities. Despite this interest, comprehensive studies focusing on genomic traits governing plant growth and stress resilience in this genus using whole-genome sequencing are still scarce. Therefore, we sequenced and compared the genomes of three endophytic Lysinibacillus irui strains isolated from Canary Island date palms with the ex-type strain IRB4-01. Overall, the genomes of these strains consist of a circular chromosome with an average size of 4.6 Mb and a GC content of 37.2%. Comparative analysis identified conserved gene clusters within the core genome involved in iron acquisition, phosphate solubilization, indole-3-acetic acid biosynthesis, and volatile compounds. In addition, genome analysis revealed the presence of genes encoding carbohydrate-active enzymes, and proteins that confer resistance to oxidative, osmotic, and salinity stresses. Furthermore, pathways of putative novel bacteriocins were identified in all genomes. This illustrates possible common plant growth-promoting traits shared among all strains of L. irui. Our findings highlight a rich repertoire of genes associated with plant lifestyles, suggesting significant potential for developing inoculants to enhance plant growth and resilience. This study is the first to provide insights into the overall genomic signatures and mechanisms of plant growth promotion and biocontrol in the genus Lysinibacillus.Key points• Pioneer study in elucidating plant growth promoting in L. irui through comparative genomics.• Genome mining identified biosynthetic pathways of putative novel bacteriocins.• Future research directions to develop L. irui-based biofertilizers for sustainable agriculture.

Trichoderma-secreted anthranilic acid promotes lateral root development via auxin signaling and RBOHF-induced endodermal cell wall remodeling

Trichoderma spp. have evolved the capacity to communicate with plants by producing various secondary metabolites (SMs). Nonhormonal SMs play important roles in plant root development, while specific SMs from rhizosphere microbes and their underlying mechanisms to control plant root branching are still largely unknown. In this study, a compound, anthranilic acid (2-AA), is identified from T.guizhouense NJAU4742 to promote lateral root development. Further studies demonstrate that 2-AA positively regulates auxin signaling and transport in the canonical auxin pathway. 2-AA also partly rescues the lateral root numbers of CASP1pro:shy2-2, which regulates endodermal cell wall remodeling via an RBOHF-induced reactive oxygen species burst. In addition, our work reports another role for microbial 2-AA in the regulation of lateral root development, which is different from its better-known role in plant indole-3-acetic acid biosynthesis. In summary, this study identifies 2-AA from T.guizhouense NJAU4742, which plays versatile roles in regulating plant root development.

An auxin research odyssey: 1989-2023.

The phytohormone auxin is at times called the master regulator of plant processes and has been shown to be a central player in embryo development, the establishment of the polar axis, early aspects of seedling growth, as well as growth and organ formation during later stages of plant development. The Plant Cell has been key, since the inception of the journal, to developing an understanding of auxin biology. Auxin-regulated plant growth control is accomplished by both changes in the levels of active hormones and the sensitivity of plant tissues to these concentration changes. In this historical review, we chart auxin research as it has progressed in key areas and highlight the role The Plant Cell played in these scientific developments. We focus on understanding auxin-responsive genes, transcription factors, reporter constructs, perception, and signal transduction processes. Auxin metabolism is discussed from the development of tryptophan auxotrophic mutants, the molecular biology of conjugate formation and hydrolysis, indole-3-butyric acid metabolism and transport, and key steps in indole-3-acetic acid biosynthesis, catabolism, and transport. This progress leads to an expectation of a more comprehensive understanding of the systems biology of auxin and the spatial and temporal regulation of cellular growth and development.

Comparative transcriptome analysis revealed that auxin and cell wall biosynthesis play important roles in the formation of hollow hearts in cucumber

BackgroundHollow heart is a kind of physiological defect that seriously affects the yield, quality, and economic value of cucumber. However, the formation of hollow hearts may relate to multiple factors in cucumber, and it is necessary to conduct analysis.ResultsIn this study, hollow and non-hollow fruits of cucumber K07 were used for comparative transcriptome sequencing and analysis. 253 differentially expressed genes and 139 transcription factors were identified as being associated with the formation of hollow hearts. Hormone (auxin) signaling and cell wall biosynthesis were mainly enriched in GO and KEGG pathways. Expression levels of key genes involved in indole-3-acetic acid biosynthesis in carpel were lower in the hollow fruits than non-hollow fruits, while there was no difference in the flesh. The concentration of indole-3-acetic also showed lower in the carpel than flesh. The biosynthetic pathway and content analysis of the main components of the cell wall found that lignin biosynthesis had obvious regularity with hollow heart, followed by hemicellulose and cellulose. Correlation analysis showed that there may be an interaction between auxin and cell wall biosynthesis, and they collectively participate in the formation of hollow hearts in cucumber. Among the differentially expressed transcription factors, MYB members were the most abundant, followed by NAC, ERF, and bHLH.ConclusionsThe results and analyses showed that the low content of auxin in the carpel affected the activity of enzymes related to cell wall biosynthesis at the early stage of fruit development, resulting in incomplete development of carpel cells, thus forming a hollow heart in cucumber. Some transcription factors may play regulatory roles in this progress. The results may enrich the theory of the formation of hollow hearts and provide a basis for future research.

High prevalence of heteroresistance in Staphylococcus aureus is caused by a multitude of mutations in core genes.

Heteroresistance (HR) is an enigmatic phenotype where, in a main population of susceptible cells, small subpopulations of resistant cells exist. This is a cause for concern, as this small subpopulation is difficult to detect by standard antibiotic susceptibility tests, and upon antibiotic exposure the resistant subpopulation may increase in frequency and potentially lead to treatment complications or failure. Here, we determined the prevalence and mechanisms of HR for 40 clinical Staphylococcus aureus isolates, against 6 clinically important antibiotics: daptomycin, gentamicin, linezolid, oxacillin, teicoplanin, and vancomycin. High frequencies of HR were observed for gentamicin (69.2%), oxacillin (27%), daptomycin (25.6%), and teicoplanin (15.4%) while none of the isolates showed HR toward linezolid or vancomycin. Point mutations in various chromosomal core genes, including those involved in membrane and peptidoglycan/teichoic acid biosynthesis and transport, tRNA charging, menaquinone and chorismite biosynthesis and cyclic-di-AMP biosynthesis, were the mechanisms responsible for generating the resistant subpopulations. This finding is in contrast to gram-negative bacteria, where increased copy number of bona fide resistance genes via tandem gene amplification is the most prevalent mechanism. This difference can be explained by the observation that S. aureus has a low content of resistance genes and absence of the repeat sequences that allow tandem gene amplification of these genes as compared to gram-negative species.

The maize transcription factor CCT regulates drought tolerance by interacting with Fra a 1, E3 ligase WIPF2, and auxin response factor Aux/IAA8.

Plants are commonly exposed to abiotic stressors, which can affect their growth, productivity, and quality. Previously, the maize transcription factor ZmCCT was shown to be involved in the photoperiod response, delayed flowering, and quantitative resistance to Gibberella stalk rot. In this study, we demonstrate that ZmCCT can regulate plant responses to drought. ZmCCT physically interacted with ZmFra a 1, ZmWIPF2, and ZmAux/IAA8, which localized to the cell membrane, cytoplasm, and nucleus, respectively, both in vitro and in vivo in a yeast two-hybrid screen in response to abiotic stress. Notably, ZmCCT recruits ZmWIPF2 to the nucleus, which has strong E3 self-ubiquitination activity dependent on its RING-H2 finger domain in vitro. When treated with higher indole-3-acetic acid/abscisic acid ratios, the height and root length of Y331-ΔTE maize plants increased. Y331-ΔTE plants exhibited increased responses to exogenously applied auxin or ABA compared to Y331 plants, indicating that ZmCCT may be a negative regulator of ABA signalling in maize. In vivo, ZmCCT promoted indole-3-acetic acid biosynthesis in ZmCCT-overexpressing Arabidopsis. RNA-sequencing and DNA affinity purification-sequencing analyses showed that ZmCCT can regulate the expression of ZmRD17, ZmAFP3, ZmPP2C, and ZmARR16 under drought. Our findings provide a detailed overview of the molecular mechanism controlling ZmCCT functions and highlight that ZmCCT has multiple roles in promoting abiotic stress tolerance.

Regulation of indole-3-acetic acid biosynthesis and consequences of auxin production deficiency in Serratia plymuthica.

Indole-3-acetic acid (IAA) is emerging as a key intra- and inter-kingdom signal molecule that modulates a wide range of processes of importance during plant-microorganism interaction. However, the mechanisms by which IAA carries out its functions in bacteria as well as the regulatory processes by which bacteria modulate auxin production are largely unknown. Here, we found that IAA synthesis deficiency results in important global transcriptional changes in the broad-range antibiotic-producing rhizobacterium Serratia plymuthica A153. Most pronounced transcriptional changes were observed in various gene clusters for aromatic acid metabolism, including auxin catabolism. To delve into the corresponding molecular mechanisms, different regulatory proteins were biochemically characterized. Among them, a TyrR orthologue was essential for IAA production through the activation of the ipdc gene encoding a key enzyme for IAA biosynthesis. We showed that TyrR specifically recognizes different aromatic amino acids which, in turn, alters the interactions of TyrR with the ipdc promoter. Screening of mutants defective in various transcriptional and post-transcriptional regulators allowed the identification of additional regulators of IAA production, including PigP and quorum sensing-related genes. Advancing our knowledge on the mechanisms that control the IAA biosynthesis in beneficial phytobacteria is of biotechnological interest for improving agricultural productivity and sustainable agricultural development.

Taxonomic Study of Three Novel Paenibacillus Species with Cold-Adapted Plant Growth-Promoting Capacities Isolated from Root of Larix gmelinii.

Exploration of the novel species of the genus Paenibacillus with plant-growth promoting characteristics at the low-temperature environment is of great significance for the development of psychrotolerant biofertilizer in forestry and agriculture. During the course of isolation of root endophytes of Larix gmelinii in the island frozen soil, three strains designated as T3-5-0-4, N1-5-1-14 and N5-1-1-5 were isolated. The three strains showed plant growth-promoting properties at the low temperature, such as phosphate solubilization, indole-3-acetic acid biosynthesis and siderophore production. According to pairwise sequence analyses of the 16S rRNA genes, the three strains represent putatively novel taxa within the genus Paenibacillus. The strains have typical chemotaxonomic characteristics of the genus Paenibacillus by having meso-diaminopimelic acid as diagnostic diamino acid, anteiso-C15:0 as the predominant fatty acid and MK-7 as the predominant menaquinone. The polar lipid profiles of all strains contained diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. The sizes of the genomes of the stains ranged from 5.66 to 9.07 Mb and the associated G+C contents ranged from 37.9% to 44.7%. Polyphasic taxonomic study including determination of genome relatedness indices revealed that the strains are representatives of three novel species in the genus Paenibacillus. Consequently, isolates T3-5-0-4, N1-5-1-14 and N5-1-1-5 are proposed as novel species for which the names of Paenibacillus endoradicis sp. nov. (CFCC15691T = KCTC43441T), Paenibacillus radicibacter sp. nov, (CFCC15694T = KCTC43442T) and Paenibacillus radicis sp. nov. (CFCC15710T = KCTC43173T), respectively. Moreover, analysis for biosynthetic genes showed that the strains have potential for plant growth-promoting characteristics, plant rhizospheres colonization and low-temperature adaption, most of which are consistent with the results of the bioactivity test.

Mechanism of S-Adenosyl-l-methionine C-Methylation by Cobalamin-dependent Radical S-Adenosyl-l-methionine Methylase in 1-Amino-2-methylcyclopropanecarboxylic Acid Biosynthesis.

The radical S-adenosyl-l-methionine (SAM) methylase Orf29 catalyzes the C-methylation of SAM in the biosynthesis of 1-amino-2-methylcyclopropanecarboxylic acid. Here, we determined that the methylation product is (4″R)-4″-methyl-SAM. Furthermore, we found that the 5'-deoxyadenosyl radical generated by Orf29 abstracts the pro-R hydrogen atom from the C-4″ position of SAM to generate the radical intermediate, which reacts with methylcobalamin to give (4″R)-4″-methyl-SAM. Consequently, the Orf29-catalyzed C-methylation was confirmed to proceed with retention of configuration.

Improving berry quality and antioxidant ability in 'Ruidu Hongyu' grapevine through preharvest exogenous 2,4-epibrassinolide, jasmonic acid and their signaling inhibitors by regulating endogenous phytohormones.

Grape berries contain a variety of metabolites, such as anthocyanins, sugars, fatty acids, and antioxidants. Endogenous phytohormones strongly influence these metabolites, which regulate berry quality improvement. In this study, we evaluated the effects of 2,4-epibrassinolide (EBR, brassinolide (BR)-like growth regulator), jasmonic acid (JA), and their signaling inhibitors brassinazole (Brz), and sodium diethyldithiocarbamate (DIECA) on berry quality and antioxidant ability. Overall, the pre-harvest application of 0.5 mg L-1 EBR and 100 μmol L-1 JA significantly influences the quality of the grape berry. Results showed that EBR was superior to other treatments at enhancing the content of different metabolites, including anthocyanins, fructose, glucose, and a variety of fatty acids, in grapes. EBR and JA also enhanced the synthesis of gibberellin3 (GA3), cytokinin (CTK), salicylic acid (SA), JA, methyl jasmonate (MeJA), BR, and abscisic acid (ABA), while inhibiting the synthesis of auxin (IAA). Most genes related to BR/JA and anthocyanins/sugars/fatty acids biosynthesis were up-regulated. The effects of Brz and DIECA on the grape berry quality were totally reversed throughout the study, as shown by EBR and JA. According to correlation analysis, EBR and JA have a beneficial positive interaction that promotes the formation of strong coherences in grape berries between ABA/IAA/ZT-fruit expansion, BR/JA/MeJA/GA3/ZR-biochemical characteristics development, JA/MeJA/ABA/GA3/SA/ZR-antioxidant capacity enhancement, and JA/MeJA/IAA/GA3/ZT/ZR-fatty acids accumulation. In this regard, we concluded that preharvest exogenous 0.5 mg L-1 EBR and 100 μmol L-1 JA is a successful way to improve grape berry quality.

The key role of indole-3-acetic acid biosynthesis by Bacillus thuringiensis RZ2MS9 in promoting maize growth revealed by the ipdC gene knockout mediated by the CRISPR-Cas9 system

The bacterial biosynthesis of indole-3-acetic acid (IAA) is often related to the beneficial effects of plant growth-promoting rhizobacteria (PGPR) on plant development. In PGPR belonging to the Bacillus genus, the synthesis of IAA may occur through different metabolic pathways that are still poorly understood. B. thuringiensis (Bt) is well known for its insecticidal properties; however, its beneficial features are not limited to pest control. Our group has been studed the beneficial effects of Bt strain RZ2MS9 as growth promoter in a range of plant crops, including soybean, tomato, and maize. We recently demonstrated that bacterial IAA biosynthesis plays an important role in the ability of RZ2MS9 to benefit plant development. However, the molecular involved mechanisms in the IAA biosynthesis by this bacterium in the beneficial interaction with plants remain unclear. Here, we investigated the genetic basis of IAA biosynthesis by RZ2MS9. We knocked out the ipdC gene, involved in IAA biosynthesis via the tryptophan-dependent IPyA pathway, using the CRISPR-Cas9 system. Our results showed that, by disrupting the IPyA pathway, the amount of IAA synthesized by the mutant RZ2MS9 (ΔipdC) in the presence of tryptophan drops 57%. The gene knockout did not affect the bacterial growth, but it did affect its ability to colonize maize. Moreover, deactivating the ipdC gene in RZ2MS9 significantly reduces its ability to promote maize growth. ΔipdC performed worse than RZ2MS9 in almost all evaluated plant parameters, including total root length, projected root area, lateral roots, aerial part dry matter, and germination speed index. Therefore, we demonstrated that tryptophan-dependent IAA biosynthesis via the IPyA pathway by RZ2MS9 is strongly influenced by the ipdC gene. Furthermore, IAA biosynthesis by RZ2MS9 is a major mechanism used by this PGPR to promote maize growth.

Non-aflatoxigenic kojic acid-producing Aspergillus flavus NJC04 reduces the symptoms of Sclerotinia sclerotiorum in soybean

Although non-aflatoxigenic Aspergillus flavus strains have been thoroughly used to reduce aflatoxin contaminations in maize and nuts, the biocontrol potential of these strains for the management of fungal pathogens remains almost unexplored. This study aimed to evaluate the biocontrol mechanisms and efficacy of A. flavus NJC04, which was previously isolated from kiwifruit, for the control of soybean pathogen Sclerotinia sclerotiorum. Non-aflatoxigenic NJC04 was shown to contain important deletions in the aflatoxin and cyclopiazonic acid biosyntheses. Interestingly, this strain inhibited mycelial growth and sclerotia formation of soybean pathogen Sclerotinia sclerotiorum. NJC04 showed various antifungal mechanisms against S. sclerotiorum, including competition for space and nutrients, and the production of antifungal kojic acid, which was detected at 87 ± 4 mg/L in the culture medium. NJC04 colonized soybean plants during long periods and did not cause necrotic lesions. Preventive application of 1 × 107 and 1 × 108 NJC04 spores/mL reduced Sclerotinia rot symptoms by 83.2 % and 100 %, respectively. Collectively, the biocontrol efficacy of non-aflatoxigenic NJC04 for the control of S. sclerotiorum was examined for the first time revealing new insights into the mechanisms used by A. flavus strains to compete with plant fungal pathogens.

OsPP65 Negatively Regulates Osmotic and Salt Stress Responses Through Regulating Phytohormone and Raffinose Family Oligosaccharide Metabolic Pathways in Rice

Although type 2C protein phosphatases (PP2Cs) have been demonstrated to play important roles in regulating plant development and various stress responses, their specific roles in rice abiotic stress tolerance are still largely unknown. In this study, the functions of OsPP65 in rice osmotic and salt stress tolerance were investigated. Here, we report that OsPP65 is responsive to multiple stresses and is remarkably induced by osmotic and salt stress treatments. OsPP65 was highly expressed in rice seedlings and leaves and localized in the nucleus and cytoplasm. OsPP65 knockout rice plants showed enhanced tolerance to osmotic and salt stresses. Significantly higher induction of genes involved in jasmonic acid (JA) and abscisic acid (ABA) biosynthesis or signaling, as well as higher contents of endogenous JA and ABA, were observed in the OsPP65 knockout plants compared with the wild-type plants after osmotic stress treatment. Further analysis indicated that JA and ABA function independently in osmotic stress tolerance conferred by loss of OsPP65. Moreover, metabolomics analysis revealed higher endogenous levels of galactose and galactinol but a lower content of raffinose in the OsPP65 knockout plants than in the wild-type plants after osmotic stress treatment. These results together suggest that OsPP65 negatively regulates osmotic and salt stress tolerance through regulation of the JA and ABA signaling pathways and modulation of the raffinose family oligosaccharide metabolism pathway in rice. OsPP65 is a promising target for improvement of rice stress tolerance using gene editing.

Differential regulation of mRNAs and lncRNAs related to lipid metabolism in Duolang and Small Tail Han sheep

The function of long non-coding RNA (lncRNA) can be achieved through the regulation of target genes, and the deposition of fat is regulated by lncRNA. Fat has an important effect on meat quality. However, there are relatively few studies on lncRNAs in the subcutaneous adipose tissue of Duolang sheep and Small Tail Han sheep. In this study, RNA-Seq technology and bioinformatics methods were used to identify and analyze the lncRNA and mRNA in the subcutaneous adipose tissue of the two breeds of sheep. The results showed that 107 lnRNAs and 1329 mRNAs were differentially expressed. The differentially expressed genes and lncRNA target genes were significantly enriched in the biosynthesis of unsaturated fatty acids signaling pathway, fatty acid metabolism, adipocyte differentiation and other processes related to fat deposition. Among them, LOC105616076, LOC114118103, LOC105607837, LOC101116622, and LOC105603235 target FADS1, SCD, ELOVL6, HSD17B12 and HACD2, respectively. They play a key regulatory role in the biosynthesis of unsaturated fatty acids. This study lays a foundation for the study of the molecular mechanism of lncRNA on fat development, and has reference value for studying the differences in fat deposition between Duolang sheep and Small Tail Han sheep.

MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma

Neuroblastoma (NB) is a childhood cancer arising from sympatho-adrenal neural crest cells. MYCN amplification is found in half of high-risk NB patients; however, no available therapies directly target MYCN. Using multi-dimensional metabolic profiling in MYCN expression systems and primary patient tumors, we comprehensively characterized the metabolic landscape driven by MYCN in NB. MYCN amplification leads to glycerolipid accumulation by promoting fatty acid (FA) uptake and biosynthesis. We found that cells expressing amplified MYCN depend highly on FA uptake for survival. Mechanistically, MYCN directly upregulates FA transport protein 2 (FATP2), encoded by SLC27A2. Genetic depletion of SLC27A2 impairs NB survival, and pharmacological SLC27A2 inhibition selectively suppresses tumor growth, prolongs animal survival, and exerts synergistic anti-tumor effects when combined with conventional chemotherapies in multiple preclinical NB models. This study identifies FA uptake as a critical metabolic dependency for MYCN-amplified tumors. Inhibiting FA uptake is an effective approach for improving current treatment regimens.

Comparative physiological and metabolomic analyses reveal that Fe3O4 and ZnO nanoparticles alleviate Cd toxicity in tobacco

BackgroundHeavy metals repress tobacco growth and quality, and engineered nanomaterials have been used for sustainable agriculture. However, the underlying mechanism of nanoparticle-mediated cadmium (Cd) toxicity in tobacco remains elusive.ResultsHerein, we investigated the effects of Fe3O4 and ZnO nanoparticles (NPs) on Cd stress in tobacco cultivar ‘Yunyan 87’ (Nicotianatabacum). Cd severely repressed tobacco growth, whereas foliar spraying with Fe3O4 and ZnO NPs promoted plant growth, as indicated by enhancing plant height, root length, shoot and root fresh weight under Cd toxicity. Moreover, Fe3O4 and ZnO NPs increased, including Zn, K and Mn contents, in the roots and/or leaves and facilitated seedling growth under Cd stress. Metabolomics analysis showed that 150 and 76 metabolites were differentially accumulated in roots and leaves under Cd stress, respectively. These metabolites were significantly enriched in the biosynthesis of amino acids, nicotinate and nicotinamide metabolism, arginine and proline metabolism, and flavone and flavonol biosynthesis. Interestingly, Fe3O4 and ZnO NPs restored 50% and 47% in the roots, while they restored 70% and 63% in the leaves to normal levels, thereby facilitating plant growth. Correlation analysis further indicated that these metabolites, including proline, 6-hydroxynicotinic acid, farrerol and quercetin-3-O-sophoroside, were significantly correlated with plant growth.ConclusionsThese results collectively indicate that metal nanoparticles can serve as plant growth regulators and provide insights into using them for improving crops in heavy metal-contaminated areas.Graphical