Search

Due to their vital physiological functions, nutritional fatty acids have great potential as nutraceutical food supplements for preventing an array of diseases such as inflammation, depression, arthritis, osteoporosis, diabetes and cancer. Microbial biosynthesis of fatty acids follows the trend of sustainable development, as it enables green, environmentally friendly and efficient production. As a natural oleaginous yeast, Yarrowia lipolytica is especially well-suited for the production of fatty acids. Moreover, it has a variety of genetic engineering tools and novel metabolic engineering strategies that make it a robust workhorse for the production of an array of value-added products. In this review, we summarize recent advances in metabolic engineering strategies for accumulating nutritional fatty acids in Y. lipolytica, including conjugated fatty acids and polyunsaturated fatty acids. In addition, the future prospects of nutritional fatty acid production using the Y. lipolytica platform are discussed in light of the current progress, challenges, and trends in this field. Finally, guidelines for future studies are also emphasized.

The sesquiterpene α-humulene is an important plant natural product, which has been used in the pharmaceutical industry due to its anti-inflammatory and anticancer activities. Although phytoextraction and chemical synthesis have previously been applied in α-humulene production, the low efficiency and high costs limit the development. In this study, Yarrowia lipolytica was engineered as the robust cell factory for sustainable α-humulene production. First, a chassis with high α-humulene output in the cytoplasm was constructed by integrating α-humulene synthases with high catalytic activity, optimizing the flux of mevalonate and acetyl-CoA pathways. Subsequently, the strategy of dual cytoplasmic-peroxisomal engineering was adopted in Y. lipolytica; the best strain GQ3006 generated by introducing 31 copies of 12 different genes could produce 2280.3± 38.2 mg/l (98.7 ± 4.2 mg/g dry cell weight) α-humulene, a 100-fold improvement relative to the baseline strain. To further improve the titer, a novel strategy for downregulation of squalene biosynthesis based on Cu

Terpenes are a large class of secondary metabolites with diverse structures and functions that are commonly used as valuable raw materials in food, cosmetics, and medicine. With the development of metabolic engineering and emerging synthetic biology tools, these important terpene compounds can be sustainably produced using different microbial chassis. Currently, yeasts such as

We used mechanism-informed phenotypic screening to identify and optimize compounds that phenocopy the genetic depletion of the mitotic aurora kinase B (AURKB) kinase. After assaying nine aryl fused seven-membered lactam compounds, we identified a hit compound

Trehalose is important in activity, development, and environmental-stress response, especially in invertebrates. It is mainly synthesized by trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP), and degraded by trehalase (TRE). In the present study, the tps, tpp, and tre were identified from various crustacean species and their phylogeny, structure, network, and transcriptome were analyzed. The tps and tpp are fused in crustaceans, accompanied with multi-copies of genes to improve the synthesis capacity of trehalose, and they may be formed by whole-genome duplication (WGD) and/or segmental duplications. Phylogenetic subgroups of enzymes in the same species may be due to the different lengths and distribution positions of domains. The protein with single TPP domain in the salmon louse, the copepod Lepeophtheirus salmonis (Krøyer, 1837), probably has a depoisoning effect. Structure analyses and location predictions showed that crustacean TRE possess an α-helix-rich structure with barrel core, and are membrane-bound, cytoplasmic, and secreted. Additionally, the non-acid TRE might not be adjusted by Ca2+ because there is no binding domain in crustaceans. Expression profiles of different tissues, developmental periods, and environmental-challenge responses, as well as genes of co-expression networks suggested that TPS (including TPP) and TRE might play important roles in physiological activities including development and environmental adaptation in crustaceans. Multi-copies of tre may enhance survival ability of copepods in diverse and sometimes harsh environments. Branchiopods, copepods, and the marine shrimp Penaeus vannamei Boone, 1931 are suspected to adopt possible acid TRE as a supplementary strategy in response to stress.

Therapeutic targeting of MYC directly has proven difficult, but several means to target MYC indirectly using a synthetic lethal drug approach have been proposed. Synthetic lethal approaches for MYC have sought to take advantage of vulnerabilities MYC imposes related to either metabolic reprogramming, apoptotic signaling or the cycling of cancer cells. Here, we describe in detail the cell division phenotypes induced by a MYC synthetic lethal compound, dimethylfasudil (diMF). DiMF is a known ROCK inhibitor, but structurally related ROCK inhibitors are not synthetic lethal with MYC, so the activity of diMF is not related to blockade of this family of kinases. Instead, this compound induced multiple cell cycle-related liabilities. These included the early mitotic arrest of cycling cells followed by mitotic catastrophe-induced death and the induction of polyploidy in cells that do manage to pass through mitosis. As early as prometaphase, we noted diminished staining for BUB1 kinase, which binds to kinetochores and regulates the mitotic spindle checkpoint and chromosome congression. Kinetochore proteins, such as CENP-F, failed to localize at the metaphase plate, confirming a deficit in centromere assembly. This, presumably, contributed to the development of segregation anomalies in diMF-treated cells. In anaphase cells, the protein regulator of cytokinesis 1 (PRC1), failed to be recruited to the midzone, leading to a cascade of defects that included failed recruitment of the chromosomal passenger protein complex, the centralspindlin complex and polo-like-kinase 1 (PLK1). These observations correlate well with the cell death phenotypes induced by diMF, which may serve as a prototype MYC synthetic lethal compound to explore synthetic lethal therapy or as a scaffold upon which to build superior compounds. The phenotypes described here serve as examples of MYC synthetic lethal drug effects that can be used to explore and maximize drug discovery programs.

Supplementary Figure from Integrative Genomic Profiling Uncovers Therapeutic Targets of Acral Melanoma in Asian Populations

Supplementary Data from Synergistic Antitumor Effect of the Activated PPARγ and Retinoid Receptors on Human Osteosarcoma

Purpose: Osteosarcoma is the most common primary malignancy of bone. The long-term survival of osteosarcoma patients hinges on our ability to prevent and/or treat recurrent and metastatic lesions. Here, we investigated the activation of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid receptors as a means of differentiation therapy for human osteosarcoma.Experimental Design: We examined the endogenous expression of PPARγ and retinoid receptors in a panel of osteosarcoma cells. Ligands or adenovirus-mediated overexpression of these receptors were tested to inhibit proliferation and induce apoptosis of osteosarcoma cells. Osteosarcoma cells overexpressing the receptors were introduced into an orthotopic tumor model. The effect of these ligands on osteoblastic differentiation was further investigated.Results: Endogenous expression of PPARγ and isotypes of retinoic acid receptor (RAR) and retinoid X receptor (RXR) is detected in most osteosarcoma cells. Troglitazone, 9-cis retinoic acid (RA), and all-trans RA, as well as overexpression of PPARγ, RARα, and RXRα, inhibit osteosarcoma cell proliferation and induce apoptosis. A synergistic inhibitory effect on osteosarcoma cell proliferation is observed between troglitazone and retinoids, as well as with the overexpression pairs of PPARγ/RARα, or PPARγ/RXRα. Overexpression of PPARγ, RARα, RXRα, or in combinations inhibits osteosarcoma tumor growth and cell proliferation in vivo. Retinoids (and to a lesser extent, troglitazone) are shown to promote osteogenic differentiation of osteosarcoma cells and mesenchymal stem cells.Conclusions: Activation of PPARγ, RARα, and RXRα may act synergistically on inhibiting osteosarcoma cell proliferation and tumor growth, which is at least partially mediated by promoting osteoblastic differentiation of osteosarcoma cells. Clin Cancer Res; 16(8); 2235–45. ©2010 AACR.

Supplementary figures, tables and figure legends

Purpose:Enhanced lipogenesis and mitochondrial function are two critical metabolic characteristics in melanoma, but their crosstalk involved in tumor biology and targeted therapy remains unknown. ATP-citrate lyase (ACLY) is a crucial lipogenic enzyme that is greatly implicated in tumor development, but its role in mitochondrial function and melanoma pathogenesis has not been elucidated.Experimental Design:In vitro and in vivo functional experiments were performed to determine the effect of ACLY on melanoma growth. mRNA expression profile analysis and a panel of biochemical assays were used to investigate the role of ACLY in mitochondrial oxidative phosphorylation and the underlying mechanism. The effect of combined ACLY inhibition on the efficacy of MAPK inhibition therapy was also examined.Results:We first found that ACLY expression was increased in melanoma and facilitated cell proliferation and tumor growth both in vitro and in vivo. Subsequent mRNA expression profile analysis and functional studies unveiled that ACLY specifically activated MITF–PGC1α axis to promote mitochondrial biogenesis and melanoma growth. Mechanistically, ACLY enhanced the activity of acetyltransferase P300, increasing the histone acetylation at MITF locus to promote MITF–PGC1α axis transcription. More importantly, the combined inhibition of ACLY sensitized BRAF-mutant melanoma to MAPK inhibition by suppressing MITF–PGC1α axis.Conclusions:We demonstrate that ACLY epigenetically potentiates oxidative phosphorylation to promote melanoma growth and MAPK inhibition adaptive resistance. Our study discovers the novel crosstalk between lipogenesis and mitochondrial function in tumor biology and highlights targeting ACLY as a potent therapeutic approach via simultaneously impairing tumor growth and MAPK inhibition resistance in melanoma.

mRNA expression profile analysis

Purpose:Acral melanoma is the major subtype of melanoma seen in Asian patients with melanoma and is featured by its insidious onset and poor prognosis. The genomic study that elucidates driving mutational events is fundamental to the development of gene-targeted therapy. However, research on genomic profiles of acral melanoma in Asian patients is still sparse.Experimental Design:We carried out whole-exome sequencing (WES) on 60 acral melanoma lesions (with 55 primary samples involved), targeted deep sequencing in a validation cohort of 48 cases, RNA sequencing in 37 acral melanoma samples (all from the 60 undergoing WES), and FISH in 233 acral melanoma specimens (54 of the 60 undergoing WES included). All the specimens were derived from Asian populations.Results:BRAF, NRAS, and KIT were discerned as significantly mutated genes (SMG) in acral melanoma. The detected COSMIC signature 3 related to DNA damage repair, along with the high genomic instability score, implied corresponding pathogenesis of acral melanoma. Moreover, the copy number gains of EP300 were associated with the response of acral melanoma to targeted therapy of A485 (a p300 inhibitor) and immune checkpoint blockade treatment. In addition, the temporal order in mutational processes of the samples was reconstructed, and copy-number alterations were identified as early mutational events.Conclusions:Our study provided a detailed view of genomic instability, potential therapeutic targets, and intratumoral heterogeneity of acral melanoma, which might fuel the development of personalized strategies for treating acral melanoma in Asian populations.

Supplementary Data from Integrative Genomic Profiling Uncovers Therapeutic Targets of Acral Melanoma in Asian Populations

Supplementary Table 1 from Repression of 15-Hydroxyprostaglandin Dehydrogenase Involves Histone Deacetylase 2 and Snail in Colorectal Cancer

Supplementary Figure Legends 1-2 from Repression of 15-Hydroxyprostaglandin Dehydrogenase Involves Histone Deacetylase 2 and Snail in Colorectal Cancer

Supplementary Figure 2 from Repression of 15-Hydroxyprostaglandin Dehydrogenase Involves Histone Deacetylase 2 and Snail in Colorectal Cancer

Supplementary Figure 1 from Repression of 15-Hydroxyprostaglandin Dehydrogenase Involves Histone Deacetylase 2 and Snail in Colorectal Cancer

The purpose of this study is to use an integrated data mining approach, in which multi-omics, clinical information, and image information are considered together, and to develop a new prognosis prediction model for Lung Squamous Cell Carcinoma (LUSC). We analyzed Reverse Phase Protein Array (RPPA) data of LUSC samples (n = 328) from The Cancer Genome Atlas cohort (TCGA). Univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis followed by multivariate Cox analysis were performed to identify key protein candidates and constructed a robust multiprotein prognostic model on the training set. The optimal cut-off value was obtained by the receiver operating characteristic (ROC) curve, which was employed to divide patients into a high- and a low-risk group. The model was evaluated using multiple statistical methods, including principal components analysis (PCA), Kaplan-Meier survival analysis, independent prognostic analysis, ROC analysis, and immunohistochemistry (IHC) staining. The co-expression analysis and bioinformatics enrichment analysis of gene function was adapted to evaluate the prognostic effect and biological pathways of the model. Four-protein (Histone-H3, HSP27_pS82, CHK2, and PAXILLIN) prognostic signature was able to stratify patients into high- and low-risk groups with statistical significance. The signature estimates poor overall survival for high-risk patients in both training and testing sets. Histone-H3, HSP27_pS82, and CHK2 were found to be protective, while PAXILLIN was associated with poor prognosis. Univariate and multivariate Cox regression analysis showed that the risk model was an independent risk factor for overall survival (univariate: HR = 3.558, 95%CI = 2.451–5.169, p< 0.001, multivariate: HR = 2.515, 95%CI = 1.750–3.615, p < 0.001). The area under the curve (AUC) of the risk scores was 0.742. The correlation heatmap provided a landscape for 455 proteins. The gene set enrichment analysis (GSEA) results revealed that adhesion molecular and cancer pathways were enriched in the high-risk group and the cytochrome P450 pathway was enriched in the low-risk groups. Our finding discovered a set of novel 4-related prognostic signatures could serve as a sensitive independent prognostic factor for individualized survival predictions.

Endosymbionts live symbiotically with insect hosts and play important roles in the evolution, growth, development, reproduction, and environmental fitness of hosts. Weevils are one of the most abundant insect groups that can be infected by various endosymbionts, such as Sodalis, Nardonella, and Wolbachia. The sweet potato weevil, Cylas formicarius (Coleoptera: Brentidae), is a notorious pest in sweet potato (Ipomoea batatas L.) cultivation. Currently, little is known about the presence of endosymbionts in C. formicarius. Herein, we assessed the endosymbiont load of a single geographic population of C. formicarius. The results showed that Nardonella and Rickettsia could infect C. formicarius at different rates, which also varied according to the developmental stages of C. formicarius. The relative titer of Nardonella was significantly related to C. formicarius developmental stages. The Nardonella-infecting sweet potato weevils were most closely related to the Nardonella in Sphenophorus levis (Coleoptera, Curculionidae). The Rickettsia be identified in bellii group. These results preliminarily revealed the endosymbionts in C. formicarius and helped to explore the diversity of endosymbionts in weevils and uncover the physiological roles of endosymbionts in weevils.

Purpose: Acral melanoma is the major subtype of melanoma seen in Asian patients with melanoma and is featured by its insidious onset and poor prognosis. The genomic study that elucidates driving mutational events is fundamental to the development of gene-targeted therapy. However, research on genomic profiles of acral melanoma in Asian patients is still sparse. Experimental Design: We carried out whole-exome sequencing (WES) on 60 acral melanoma lesions (with 55 primary samples involved), targeted deep sequencing in a validation cohort of 48 cases, RNA sequencing in 37 acral melanoma samples (all from the 60 undergoing WES), and FISH in 233 acral melanoma specimens (54 of the 60 undergoing WES included). All the specimens were derived from Asian populations. Results: BRAF, NRAS, and KIT were discerned as significantly mutated genes (SMG) in acral melanoma. The detected COSMIC signature 3 related to DNA damage repair, along with the high genomic instability score, implied corresponding pathogenesis of acral melanoma. Moreover, the copy number gains of EP300 were associated with the response of acral melanoma to targeted therapy of A485 (a p300 inhibitor) and immune checkpoint blockade treatment. In addition, the temporal order in mutational processes of the samples was reconstructed, and copy-number alterations were identified as early mutational events. Conclusions: Our study provided a detailed view of genomic instability, potential therapeutic targets, and intratumoral heterogeneity of acral melanoma, which might fuel the development of personalized strategies for treating acral melanoma in Asian populations.

BACKGROUND The COVID-19 outbreak has gradually become more normal. College students, one of the groups most affected by the epidemic, often suffer from varying degrees of psychological problems. The prevention and improvement of college students' psychological problems are particularly important for both individuals and society. OBJECTIVE The purpose of this study was to explore (1) the changes in college students’ negative emotions during the epidemic containment period, (2) the correlation between negative emotions and healthy behaviors, and (3) the main factors that can affect negative emotions in healthy behaviors. METHODS A total of 5872 Chinese college students was selected as subjects in this study. The negative emotion Scale (DASS-21) and the health Behavior Scale (HPLP-Ⅱ) were used to investigate the level of negative emotions and health behaviors on November 12, 2021, and June 17, 2022, respectively. RESULTS The results obtained in this study have shown the significant differences between negative emotions and health behavior scores at two-time points. And there was a negative correlation between negative emotions and health behaviors. The former negative emotions can predict later health behaviors, and the former health behaviors can predict later negative emotions. In addition, stress management, spiritual growth, and responsibility for health in health behaviors have a strong correlation with negative emotions, which are the main influencing factors to reduce negative emotions in college students. CONCLUSIONS The results of this study suggest that the psychological problems of college students have become particularly serious under the dual influence of campus lockdown and academic pressure during the epidemic. Positive health behaviors may be beneficial to reduce the negative emotions of college students. Therefore, we should pay more attention to their mental health problems by reminding and guiding them to adopt a healthy lifestyle, to prevent and improve the mental health problems that they may have been accumulating, and for supporting them when necessary.

We investigated a novel 4-phenoxy-quinoline-based scaffold that mislocalizes the essential mitotic kinase, AURKB. Here, we evaluated the impact of halogen substitutions (F, Cl, Br, I) on this scaffold with respect to various drug parameters. Br-substitutedLXY18was found to be a potent and orally bioavailable disruptor of cell division, at sub-nanomolar concentrations.LXY18prevents cytokinesis by blocking AURKB relocalization in mitosis and exhibits broad-spectrum antimitotic activityin vitro. With a favorable PK profile, it shows widespread tissue distribution including the blood-brain barrier penetrance and effective accumulation in tumor tissues. More importantly, it markedly suppresses tumor growth. The novel mode of action ofLXY18may eliminate some drawbacks of direct catalytic inhibition of AURKs. Successful development ofLXY18as a clinical candidate for cancer treatment could enable a new, less toxic means of antimitotic attack that avoids drug resistance mechanisms.

As a major mediator of cellular response to viral infection in mammals, Toll-like receptor 3 (TLR3) was proved to respond to double-stranded RNA (dsRNA). However, the molecular mechanism by which TLR3 functions in the viral infection response in teleosts remains to be investigated. In this study, the Toll-like receptor 3 gene of the hybrid yellow catfish was identified and characterized by comparative genomics. Furthermore, multiple sequence alignment, genomic synteny and phylogenetic analysis suggested that the homologous TLR3 genes were unique to teleosts. Gene structure analysis showed that five exons and four introns were common components of TLR3s in the 12 examined species, and interestingly the third exon in teleosts was the same length of 194 bp. Genomic synteny analysis indicated that TLR3s were highly conserved in various teleosts, with similar organizations of gene arrangement. De novo predictions showed that TLR3s were horseshoe-shaped in multiple taxa except for avian (with a round-shaped structure). Phylogenetic topology showed that the evolution of TLR3 was consistent with the evolution of the studied species. Selection analysis showed that the evolution rates of TLR3 proteins were usually higher than those of TLR3-TIR domains, indicating that the latter were more conserved. Tissue distribution analysis showed that TLR3s were widely distributed in the 12 tested tissues, with the highest transcriptions in liver and intestine. In addition, the transcription levels of TLR3 were significantly increased in immune-related tissues after infection of exogenous Aeromonas hydrophila and poly (I:C). Molecular docking showed that TLR3 in teleosts forms a complex with poly (I:C). In summary, our present results suggest that TLR3 is a pattern recognition receptor (PRR) gene in the immune response to pathogen infections in hybrid yellow catfish.

Silver arowana, Osteoglossum bicirrhosum, is sexually monomorphic, and its sex determination mechanism is poorly understood, which has been a major hurdle in its captive breeding. To this end, we assembled two high-quality chromosome-level genomes for each sex of silver arowana, with chromosome N50 of 10.6 Mb and 10.4 Mb in female and male, respectively. Combing re-sequencing data of 109 individuals, we identified two sex-specific SNPs and confirmed a ZW model of sex-determination in this species. Both sex-specific SNPs are located in about 26Kb upstream of foxl2 gene. Since foxl2 has been confirmed to be differentially expressed in the gonads of silver arowana, it probably plays an important role in sex determination via the cross-regulation with auxiliary genes significantly correlated to it, such as dmrt1, sox8a and cyp11a1, etc. The sex chromosomes are homomorphic with a potentially recent origin, as linkage disequilibrium analysis showed minor recombination suppression. Overall, we developed accurate molecular markers for sex identification of silver arowana in each developmental stage, subsequently improving the reproductive efficiency and further promoting the industrial development.

Diseases caused by Vibrio harveyi in shrimps have gradually become one group of the most serious threats to shrimp production, while related molecular mechanisms of infections with Vibrio harveyi are still not known well in shrimps. Here, we performed proteomic sequencing of hepatopancreas in whiteleg shrimps (Litopenaeus vannamei) infected with exogenous Vibrio harveyi, and subsequent functional annotation and calculation of differentially expressed proteins (DEPs) in this study. A total of 145 DEPs were obtained, among them 36 were up-regulated and 109 were down-regulated after the infection. Meanwhile, our results showed that after the infection of Vibrio harveyi, expression levels of a variety of C-type lectins (CTLs) were changed significantly. In-depth functional domain analysis and spatial structure prediction of these CTLs revealed that amino acid sequences and spatial structures of the C-type lectin domain (CTLD) shared by the CTL-S and IML proteins were variant, suggesting differential functions between the two CTLs. In summary, various members of the CTL family have different epidemic responses to Vibrio harveyi infection, which provides a theoretical guidance for deep-going investigations on practical immunity reactions and pathogen infections in shrimps.

The sesquiterpene α-humulene has been shown to have anti-inflammatory and anticancer activities, which has led to its vast application potential in medicine. However, α-humulene production methods including phytoextraction and chemical synthesis currently were limited to low yield, high costs, and expensive catalysts, which cannot meet the increasing market demand. In this study, Yarrowia lipolytica was developed as a robust cell factory for α-humulene production. The peroxisome in Y. lipolytica was first engineered to boost the synthesis of the sesquiterpene α-humulene. By compartmentalization of the α-humulene biosynthesis pathway, improving ATP and acetyl-CoA supply, and optimizing the gene copy numbers of rate-limiting enzymes, the engineered strain GQ2012 could produce 3.2 g/L α-humulene in a 5 L bioreactor, the highest α-humulene titer reported so far. Our study provides a valuable reference for highly sustainable production of terpenoids by peroxisome engineering in Y. lipolytica.

Striped catfish (Pangasianodon hypophthalmus ), belonging to the Pangasiidae family, has become an economically important fish with wide cultivation in Southeast Asia. Owing to the high-fat trait, it is always considered as an oily fish. In our present study, a high-quality genome assembly of the striped catfish was generated by integration of Illumina short reads, Nanopore long reads and Hi-C data. A 731.7-Mb genome assembly was finally obtained, with a contig N50 of 3.5 Mb, a scaffold N50 of 29.5 Mb, and anchoring of 98.46% of the assembly onto 30 pseudochromosomes. The genome contained 36.9% repeat sequences, and a total 18,895 protein-coding genes were predicted. Interestingly, we identified a tandem triplication of fatty acid binding protein 1 gene ( fabp1; thereby named as fabp1-1, fabp1-2 and fabp1-3 respectively), which may be related to the high fat content in striped catfish. Meanwhile, the FABP1-2 and -3 isoforms differed from FABP1-1 by several missense mutations including R126T, which may affect the fatty acid binding properties. In summary, we report a high-quality chromosome-level genome assembly of the striped catfish, which provides a valuable genetic resource for biomedical studies on the high-fat trait, and lays a solid foundation for practical aquaculture and molecular breeding of this international teleost species.

Largemouth bass (大口黑鲈(

Background α-Humulene is an important biologically active sesquiterpene, whose heterologous production in microorganisms is a promising alternative biotechnological process to plant extraction and chemical synthesis. In addition, the reduction of production expenses is also an extremely critical factor in the sustainable and industrial production of α-humulene. In order to meet the requirements of industrialization, finding renewable substitute feedstocks such as low cost or waste substrates for terpenoids production remains an area of active research. Results In this study, we investigated the feasibility of peroxisome-engineering strain to utilize waste cooking oil (WCO) for high production of α-humulene while reducing the cost. Subsequently, transcriptome analysis revealed differences in gene expression levels with different carbon sources. The results showed that single or combination regulations of target genes identified by transcriptome were effective to enhance the α-humulene titer. Finally, the engineered strain could produce 5.9 g/L α‐humulene in a 5‐L bioreactor. Conclusion To the best of our knowledge, this is the first report that converted WCO to α-humulene in peroxisome-engineering strain. These findings provide valuable insights into the high-level production of α-humulene in Y. lipolytica and its utilization in WCO bioconversion. Graphical Abstract

Arachidonic acid is an essential ω-6 polyunsaturated fatty acid, which plays a significant role in cardiovascular health and neurological development, leading to its wide use in the food and pharmaceutical industries. Traditionally, ARA is obtained from deep-sea fish oil. However, this source is limited by season and is depleting the already threatened global fish stocks. With the rapid development of synthetic biology in recent years, oleaginous fungi have gradually attracted increasing attention as promising microbial sources for large-scale ARA production. Numerous advanced technologies including metabolic engineering, dynamic regulation of fermentation conditions, and multiomics analysis were successfully adapted to increase ARA synthesis. This review summarizes recent advances in the bioengineering of oleaginous fungi for ARA production. Finally, perspectives for future engineering approaches are proposed to further improve the titer yield and productivity of ARA.

The succession of dominant species always occurs during cyanobacterial blooms because there are certain conditions for cyanobacterial blooms formed by different cyanobacteria; this results in more uncertain and complex effects in cyanobacterial blooms. However, the succession pattern and consequences of dominant species and its driving factors have not received enough attention during cyanobacteria blooms. In this study, the phytoplankton community characteristics and water environment factors of Nanpeng Reservoir, a drinking water source in Chongqing, were monitored and analyzed from April to September 2018. The results showed that:① a total of 108 species of phytoplankton belonging to 59 genera and 8 phyla were identified in Nanpeng Reservoir. Of this, 13 species of 4 phyla were identified as dominant species, among which the dominance index of

Gibberellic acid (GA3) is a plant growth hormone that plays an important role in the production of crops, fruits, and vegetables with a wide market share. Due to intrinsic advantages, liquid fermentation of Fusarium fujikuroi has become the sole method for industrial GA3 production, but the broader application of GA3 is hindered by low titer. In this study, we combined atmospheric and room-temperature plasma (ARTP) with ketoconazole-based screening to obtain the mutant strain 3-6-1 with high yield of GA3. Subsequently, the medium composition and fermentation parameters were systematically optimized to increase the titer of GA3, resulting in a 2.5-fold increase compared with the titer obtained under the initial conditions. Finally, considering that the strain is prone to substrate inhibition and glucose repression, a new strategy of fed-batch fermentation was adopted to increase the titer of GA3 to 575.13 mg/L, which was 13.86% higher than the control. The strategy of random mutagenesis combined with selection and fermentation optimization developed in this study provides a basis for subsequent research on the industrial production of GA3. Graphical Abstract

A simple and sensitive colorimetric assay for detecting organophosphorus pesticides (OPs) was developed based on 3,3',5,5'-tetramethylbenzidine (TMB)/hydrogen peroxide (H