{"title":"Generation of citric acid-hyperproducers independent of methanol effect by high-level expression of cexA encoding citrate exporter in Aspergillus tubingensis.","authors":"Isato Yoshioka, Kohtaro Kirimura","doi":"10.1093/bbb/zbae099","DOIUrl":"10.1093/bbb/zbae099","url":null,"abstract":"<p><p>Methanol reportedly stimulates citric acid (CA) production by Aspergillus niger and A. tubingensis; however, the underlying mechanisms remain unclear. Here, we elucidated the molecular functions of the citrate exporter gene cexA in relation to CA production by A. tubingensis WU-2223L. Methanol addition to the medium containing glucose as a carbon source markedly increased CA production by strain WU-2223L by 3.38-fold, resulting in a maximum yield of 65.5 g/L, with enhanced cexA expression. Conversely, the cexA-complementing strain with the constitutive expression promoter Ptef1 (strain LhC-1) produced 68.3 or 66.7 g/L of CA when cultivated without or with methanol, respectively. Additionally, strain LhC-2 harboring two copies of the cexA expression cassette produced 80.7 g/L of CA without methanol addition. Overall, we showed that cexA is a target gene for methanol in CA hyperproduction by A. tubingensis WU-2223L. Based on these findings, methanol-independent CA-hyperproducing strains, LhC-1 and LhC-2, were successfully generated.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of antifungal activity of cerium oxide nanoparticles and associated cellular responses.","authors":"Shunsuke Nishino, Sayoko Oiki, Yoshimasa Yamana, Daisuke Hagiwara","doi":"10.1093/bbb/zbae101","DOIUrl":"10.1093/bbb/zbae101","url":null,"abstract":"<p><p>Cerium oxide (CeO2) nanoparticles, as a metal oxide nanomaterial, are increasingly used for various industrial and biomedical applications. Although their cytotoxicity to bacteria and the associated mechanisms have attracted particular attention, the mechanisms behind their antifungal effects have remained unclear. This study investigated the antifungal properties of CeO2, focusing on Aspergillus oryzae. CeO2 inhibited fungal spore germination on solid substrates, and the effect was fungistatic rather than fungicidal. CeO2 inhibited fungal growth, especially under UV irradiation, and induced reactive oxygen species (ROS) production. Tocopherol reduced the intracellular ROS levels and the growth-inhibitory effects of CeO2, suggesting that ROS are involved in these growth-inhibitory effects. Transcriptomic analysis revealed upregulated expression of genes related to phospholipases and phosphate metabolism. CeO2 affected phosphate ion concentration in the medium, potentially influencing cellular responses. This research provided valuable insights into the antifungal effects of CeO2 application, which differ from those of conventional photocatalysts like TiO2.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of an engineered salt-inducible proline biosynthetic operon in a glutamic acid over-producing mutant, Halomonas elongata GOP, confers increased proline yield due to enhanced growth under high-salinity conditions.","authors":"Huynh Cong Khanh, Pulla Kaothien-Nakayama, Ziyan Zou, Hideki Nakayama","doi":"10.1093/bbb/zbae102","DOIUrl":"10.1093/bbb/zbae102","url":null,"abstract":"<p><p>L-Proline (Pro) is an essential amino acid additive in livestock and aquaculture feeds. Previously, we created a Pro overproducing Halomonas elongata HN6 by introducing an engineered salt-inducible Pro biosynthetic mCherry-proBm1AC operon and deleting a putA gene that encoded a Pro catabolic enzyme in the genome of H. elongata OUT30018. Here, we report a generation of a novel Pro overproducing H. elongata HN10 strain with improved salt tolerance and higher Pro yield by expressing the mCherry-proBm1AC operon and deleting the putA gene in the genome of a spontaneous mutant H. elongata Glutamic acid Over-Producing, which overproduces glutamic acid (Glu) that is a precursor for Pro biosynthesis. The optimal salt concentration for growth of H. elongata HN10 was found to be 7% to 8% w/v NaCl, and the average Pro yield of 166 mg/L was achieved when H. elongata HN10 was cultivated in M63 minimal medium containing 4% w/v glucose and 8% w/v NaCl.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anti-inflammatory effect of covalent PPARγ ligands that have a hybrid structure of GW9662 and a food-derived cinnamic acid derivative.","authors":"Shinano Miyazawa, Misa Sakai, Yuma Omae, Yusuke Ogawa, Hideyuki Shigemori, Yusaku Miyamae","doi":"10.1093/bbb/zbae094","DOIUrl":"10.1093/bbb/zbae094","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptor γ (PPARγ) belongs to the nuclear receptor superfamily and is involved in the inflammatory process. Previously, we synthesized the ligands of PPARγ that possess the hybrid structure of a food-derived cinnamic acid derivative (CA) and GW9662, an irreversible PPARγ antagonist. These ligands activate the transcription of PPARγ through the covalent bond formation with the Cys285 residue of PPARγ, whereas their anti-inflammatory effect has not been examined yet. Here, we show the anti-inflammatory effect of the covalent PPARγ ligands in RAW264 cells, murine macrophage-like cells. GW9662 suppressed the production of nitric oxide (NO) stimulated by lipopolysaccharide and exerted a synergistic effect in combination with CA. The compounds bearing their hybrid structure dramatically inhibited NO production and transcription of proinflammatory cytokines. A comparison study suggested that the 2-chloro-5-nitrobenzoyl group of the ligands is important for anti-inflammation. Furthermore, we synthesized an alkyne-tagged analogue that becomes an activity-based probe for future mechanistic study.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovery of an antimalarial compound, burnettiene A, with a multidrug-sensitive Saccharomyces cerevisiae screening system based on mitochondrial function inhibitory activity.","authors":"Aoi Kimishima, Atsuka Nishitomi, Iori Tsuruoka, Katsuyuki Sakai, Rei Hokari, Masako Honsho, Sota Honma, Yuki Ono, Naozumi Kondo, Hayama Tsutsumi, Yuta Kikuchi, Toshiyuki Tokiwa, Hiroki Kojima, Mayuka Higo, Kenichi Nonaka, Yuki Inahashi, Masato Iwatsuki, Shin-Ichi Fuji, Jun-Pil Jang, Jae-Hyuk Jang, Takumi Chinen, Takeo Usui, Yukihiro Asami","doi":"10.1093/bbb/zbae098","DOIUrl":"10.1093/bbb/zbae098","url":null,"abstract":"<p><p>In this paper, we describe our discovery of burnettiene A (1) as an antimalarial compound from the culture broth of Lecanicillium primulinum (current name: Flavocillium primulinum) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated as an antifungal active compound from Aspergillus burnettii. However, the antifungal activity of 1 has been revealed in only one fungal species, and the mechanism of action of 1 remains unknown. After the validation of mitochondrial function inhibitory of 1, we envisioned a new antimalarial drug discovery platform based on mitochondrial function inhibitory activity. We evaluated antimalarial activity and 1 showed antimalarial activity against Plasmodium falciparum FCR3 (chloroquine sensitive) and the K1 strain (chloroquine resistant). Our study revealed the utility of our original screening system based on a multidrug-sensitive yeast and mitochondrial function inhibitory activity for the discovery of new antimalarial drug candidates.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cocoa extract induces browning of white adipocytes and improves glucose intolerance in mice fed a high-fat diet.","authors":"Eito Yonemoto, Risa Ihara, Emi Tanaka, Takakazu Mitani","doi":"10.1093/bbb/zbae105","DOIUrl":"10.1093/bbb/zbae105","url":null,"abstract":"<p><p>Cocoa extract (CE) offers several health benefits, such as antiobesity and improved glucose intolerance. However, the mechanisms remain unclear. Adipose tissue includes white adipose tissue (WAT) and brown adipose tissue. Brown adipose tissue leads to body fat reduction by metabolizing lipids to heat via uncoupling protein 1 (UCP1). The conversion of white adipocytes into brown-like adipocytes (beige adipocytes) is called browning, and it contributes to the anti-obesity effect and improved glucose tolerance. This study aimed to evaluate the effect of CE on glucose tolerance in terms of browning. We found that dietary supplementation with CE improved glucose intolerance in mice fed a high-fat diet, and it increased the expression levels of Ucp1 and browning-associated gene in inguinal WAT. Furthermore, in primary adipocytes of mice, CE induced Ucp1 expression through β3-adrenergic receptor stimulation. These results suggest that dietary CE improves glucose intolerance by inducing browning in WAT.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isolation of microorganisms from the feces of Kitasato Yakumo beef cattle as bioactive natural product producers.","authors":"Aoi Kimishima, Atsuka Nishitomi, Naozumi Kondo, Sota Honma, Masako Honsho, Sota Negami, Serino Maruyama, Kazuki Taguchi, Hidehito Matsui, Hideaki Hanaki, Takumi Chinen, Takeo Usui, Hideki Ogasawara, Yukihiro Asami","doi":"10.1093/bbb/zbae103","DOIUrl":"10.1093/bbb/zbae103","url":null,"abstract":"<p><p>We envisioned that the rumen of Kitasato Yakumo beef cattle would contain unique microorganisms which produce bioactive compounds as their defense response to the external environment. The variety of microorganisms were collected from the feces of Kitasato Yakumo beef cattle. We evaluated the biological activity of the culture broth of the isolated strains, proving the utility of our approach.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synergistic xylan decomposition by a reducing-end xylose-releasing exo-oligoxylanase with other xylanolytic enzymes derived from Paenibacillus xylaniclasticus strain TW1.","authors":"Koki Taniguchi,Shuichi Karita,Midori Umekawa","doi":"10.1093/bbb/zbae130","DOIUrl":"https://doi.org/10.1093/bbb/zbae130","url":null,"abstract":"Paenibacillus xylaniclasticus strain TW1 is a promising tool for decomposing xylan-containing lignocellulosic biomass, since this strain possesses various genes encoding cellulolytic/hemicellulolytic enzymes. In this study, PxRex8A from the TW1 strain was found to be a reducing-end xylose-releasing exo-oligoxylanase of glycoside hydrolase family 8, which cleaves xylose from xylooligosacchrides of corn core xylan. In synergistic assay, the efficient decomposition of oat spelt xylan (OSX) and beech wood xylan was exemplified in the combination of endo β-1,4-xylanase (PxXyn11A) and PxRex8A from the TW1 strain in a molar ratio of 4:1. Furthermore, it was found that the addition of β-d-xylosidase/α-l-arabinofuranosidase (PxXyl43A) from this strain with PxXyn11A and PxRex8A achieved twice the amount of reducing sugars (1.1 mg/mL) against OSX after 24 hours compared to PxXyn11A alone (0.5 mg/mL). These results present that synergy effect of PxRex8A and PxXyl43A with PxXyn11A promotes xylan degradation into xylose.","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"β-Caryophyllene, a dietary phytocannabinoid, alleviates high-fat diet-induced hepatic steatosis in mice via AMPK activation.","authors":"Ryosuke Kamikubo,Hiroki Yoshida,Taiki Fushimi,Yuki Kamei,Mitsugu Akagawa","doi":"10.1093/bbb/zbae129","DOIUrl":"https://doi.org/10.1093/bbb/zbae129","url":null,"abstract":"β-Caryophyllene (BCP), a dietary phytocannabinoid, significantly suppresses palmitate-induced lipid accumulation in human HepG2 hepatocytes via activation of AMP-activated protein kinase (AMPK) signaling. The objective of the preset research was to assess whether oral administration of BCP alleviates obesity-induced hepatic steatosis in mice through AMPK activation. We examined the protective action of supplementation of 0.3% BCP (w/w) in a high-fat diet (HFD) on C57BL/6 J mice for 12 weeks. BCP supplementation evidently ameliorated histological hepatic steatosis features, and significantly reduced triglycerides and cholesterol levels in liver, and serum levels of aspartate aminotransferase and alanine aminotransferase as compared with non-supplemented HFD-fed mice. Immunoblotting revealed that BCP supplementation in HFD-fed mice also caused hepatic AMPK activation. Furthermore, treatment with BCP in HFD-fed mice significantly suppressed body weight gain and attenuated obesity-related phenotypes relative to the HFD mice. Our results suggest the usefulness of BCP in the prevention of obesity-related liver steatosis and liver injury.","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aurantiochytrium mutant strains exhibiting different colony colors altered the contents of squalene.","authors":"Tianjing Yang,Shohei Kubo,Darryl Joy Juntila,Yasushi Iwata,Kanako Tomita,Yoshihiro Hase,Yutaka Oono,Hiroya Araie,Kohei Yoneda,Yoshiaki Maeda,Iwane Suzuki","doi":"10.1093/bbb/zbae128","DOIUrl":"https://doi.org/10.1093/bbb/zbae128","url":null,"abstract":"Aurantiochytrium sp. 18W-13a, a marine heterotrophic protist belonging to the genus thraustochytrid, is known to accumulate high levels of squalene and carotenoids. Nowadays, the mutagenesis breeding of microorganisms is still widely practiced because the induced mutations of DNA do not involve the permanent integration of heterologous DNA sequences. Therefore, in this study, we focused on the improvement of squalene yield by mutagenesis breeding using Aurantiochytrium sp. 18W-13a. To bypass the massively laborious screening, we propose to use colony colors as the first criterion to screen mutants with high squalene accumulation, since the carotenoid and squalene synthetic pathways share an intermediate. We selected pale (white)-colored mutants after carbon ion irradiation. The white mutants exhibited larger squalene yields than twice as much of the original strain. The results clearly indicate that the present screening method with colony colors promises to obtain productive strains of squalene.","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}