cerulenin / Fermentek - LARVOL DELTA

FAS2-1280F mutation in the fatty acid synthase gene, FAS2, of Saccharomyces cerevisiae enhances caprylic acid production. (PubMed, J Gen Appl Microbiol) - "To produce new types of sake with a fruity aroma, imparted mainly by ethyl caprylate, a novel cerulenin-resistant strain, NSYC8, was isolated...Ethyl caprylate was detected in sake produced by the mutant, but not in sake produced by Kyokai S-2. The mutation enhanced production of caprylic acid and ethyl caprylate, facilitating the improvement of sake yeast strains."

Journal • FASN

Targeting Fatty Acid Synthase With Berberine Promotes IL-10 Production in Macrophages and Prevents Relapse in a Murine Colitis Model. (PubMed, FASEB J) - "The FASN inhibitor cerulenin and Fasn knockdown both attenuated berberine-induced IL-10 production, suggesting a FASN-dependent augmentation pathway. These findings indicate that berberine suppresses colitis relapse by enhancing IL-10 production in macrophages via FASN binding. Our study highlights the increase in IL-10 levels through FASN as a promising strategy for maintaining remission in patients with IBD."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • FASN • IL10

FASN for diffuse malignant peritoneal mesothelioma: a prognostic biomarker after CRS+HIPEC and a therapeutic target. (PubMed, J Transl Med) - "FASN represents a novel independent prognostic biomarker in DMPM patients undergoing CRS+HIPEC and a promising therapeutic target. Given the limited treatment options for DMPM, combination strategies incorporating FASN inhibitors with selinexor or TEAD-pathway-targeting agents, supported by existing clinical trial data, may offer a rapidly translatable therapeutic approach."

Biomarker • IO biomarker • Journal • Mesothelioma • Metabolic Disorders • Oncology • Peritoneal Mesothelioma • Solid Tumor • FASN

Pre-mRNA splicing regulates cellular dedifferentiation via lipid metabolism in a cytokinin-dependent manner in Arabidopsis. (PubMed, Plant Physiol) - "Kinetin enhanced the inhibitory effect of the lipid synthesis inhibitor cerulenin on callus formation, and rrd4-1 was hypersensitive to cerulenin. Together, our data suggest that pre-mRNA splicing regulates cytokinin-mediated cellular dedifferentiation through the regulation of lipid metabolism gene splicing."

Journal • Metabolic Disorders • SPHK2

Combination of adaptive laboratory evolution and metabolic engineering on Vibrio natriegens for efficient production of 3-hydroxypropionic acid from ethanol. (PubMed, Bioresour Technol) - "Subsequently, by optimization of promoters in the 3-HP biosynthetic pathways, rational design of background strain, and adding appropriate concentrations of cerulenin, the 3-HP biosynthesis of engineered strain was significantly improved...The concentration of 3-HP in 1 L bioreactor fermentation reached 9.94 g/L, achieving a yield of 0.258 g/g. The findings suggest that ethanol derived from synthesis gas shows tremendous promise as an excellent carbon feedstock for producing high-value biochemicals using engineered Vibrio natriegens in integrated carbon-based industrial biotechnology."

Journal

Fatty acid synthase as a novel prognostic biomarker and a potential therapeutic target in diffuse malignant peritoneal mesothelioma (AACR 2024) - "To validate FASN as a therapeutic target, we investigated the cytotoxic effects of non-selective (orlistat) and selective (cerulenin and C75) FASN inhibitors on patient-derived DMPM cell lines, both as single agents and in combination with selinexor -a selective inhibitor of the exportin chromosome maintenance protein. Compared to single agents, the combined treatments resulted in increased apoptosis response and cell cycle impairment, as indicated by caspase-dependent apoptosis activation and cell accumulation in the G2-phase. Overall, our results support the relevance of FASN as a prognostic biomarker for DMPM patients and underscore its potential as a novel therapeutic target."

Biomarker • Mesothelioma • Oncology • Peritoneal Mesothelioma • Solid Tumor • FASN

Understanding lipogenesis in bladder cancer (AACR 2024) - "CPT1 was inhibited with etomoxir, thiolase with trimetazidine, FASN with cerulenin, and ACC1 with 5-(Tetradecyloxy)-2-furoic acid (TOFA). In conclusion, inhibition of lipogenesis in BCa cell lines reduces cell viability by reducing proliferation and inducing apoptosis whereas inhibitors of ß-oxidation did not produce the same effect at relevant concentrations. These data indicate lipogenesis is a key metabolic pathway for BCa cell growth."

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • ACACA • CASP3 • FASN

Targeting fatty acid synthase suppresses tumor development in NF2/CDKN2A-deficient pleural mesothelioma. (PubMed, Cell Death Dis) - "Our drug screening assay showed that the fatty acid synthase (FASN) inhibitor cerulenin demonstrates strong and selective antiproliferative properties against NF2/CDKN2A(p16)-deficient PM cells, surpassing the effects of C75, cisplatin or pemetrexed. These findings suggest that FASN might play a role in the tumorigenesis of PM cells through the regulation of mitochondrial dynamics. This research offers a novel perspective on the potential development of precision medicine for PM."

Journal • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • Targeted Protein Degradation • CDKN2A • FASN

Spindle biochemistry responds to compressive force from the nuclear envelope to tune spindle dynamics during closed mitosis. (PubMed, bioRxiv) - "Here, we investigate how force reprograms the spindle with two approaches: chronically increasing nuclear envelope tension via the lipid synthesis inhibitor cerulenin, and acutely applying force through an optical trap...We find that while motor proteins Klp5 and Klp6 only minimally affect the spindle's response to increased nuclear envelope force, the combination of removing Ase1 and increasing nuclear envelope force together rescue spindle stability. Together, our findings reveal that nuclear force on the spindle does not merely alter its shape, but is key in regulating its biochemistry to maintain force balance."

Journal

Modulating stilbenes in peanut cells: a novel approach with metabolic modulators. (PubMed, Plant Cell Rep) - "This effect was more significant than that observed with phenylalanine and cerulenin. This research provided valuable insights into metabolic pathway regulation within peanut cells and established a novel host system as a viable platform for future stilbene production."

Journal

Fatty acid synthase may facilitate the trafficking of bovine alpha herpesvirus 1 out of the Golgi apparatus, potentially promoting viral infection. (PubMed, Microbiol Spectr) - "Knockdown of FASN protein expression using siRNAs or chemical inhibition of FASN by Cerulenin leads to reduced viral replication...Therefore, we propose that a portion of the FASN protein in the Golgi apparatus plays an important role in viral trafficking out of the Golgi, which is essential for the completion of the viral replication cycle. This represents a novel mechanism of virus infection regulation, which has not been reported in other viruses, although the FASN protein is involved in the regulation of multiple viruses through distinct mechanisms."

Journal • Infectious Disease • FASN

Synergistic targeting of FASN and HMGCS1 by cerulenin enhances tumor cell ferroptosis sensitivity through rewiring lipid metabolism and blocking GPX4 biosynthesis. (PubMed, Cancer Lett) - "In vivo, cerulenin synergized with classic ferroptosis inducer erastin to suppress xenograft tumor growth without observable toxicity. Collectively, this study revealed that cerulenin dual-targets FASN/HMGCS1 and obtained with remarkable pro-ferroptosis properties, providing a mechanistically distinct therapeutic paradigm for precision cancer therapy."

Journal • Metabolic Disorders • Oncology • FASN • GPX4 • HMGCS1 • SLC7A11

Unique metabolic regulation of micromeres contributes to gastrulation in the sea urchin embryo. (PubMed, Nat Commun) - "The specific metabolic inhibitors for sugar metabolism (2-DG), fatty acid synthesis (cerulenin), and N-linked glycosylation (tunicamycin) compromise micromeres' regulatory capacity, altering the downstream germ layer patterning in the resultant embryos...We propose that the micromere ER is sensitive to specific metabolic regulation, contributing to the inductive signaling activity. This study provides a paradigm of how ER and metabolic regulation contribute to the inductive capability of the cells."

Journal • Metabolic Disorders

Enhancing 3-hydroxypropionic acid production from recombinant Saccharomyces cerevisiae for using rice straw hydrolysate and sugar cane industrial waste as substrate. (PubMed, Synth Syst Biotechnol) - "The addition of cerulenin and acetate to the fermented medium enhanced 3-HP yield by 8 times, in which recombinant yeast produced 3-HP up to 10 g/L (0.201 gproduct/gsubstrate). The results of using rice straw hydrolysate as a carbon source indicated that Saccharomyces cerevisiae S2 produced 3-HP of 4.02 g/L, which was 0.074 gproduct/gglucose in the diluted hydrolysate. These findings provide an alternative and sustainable strategy for utilizing lignocellulosic biomass for future 3-HP production at an industrial scale."

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Vibrio cholerae can Recycle Fatty Acids Via an Acyl-Acyl Carrier Protein Synthetase. (PubMed, Curr Microbiol) - "In vitro characterization shows that the enzyme can load diverse fatty acids on the FAS acyl carrier protein as well as on coenzyme A. We show that three different FAS-targeted antibiotics can arrest growth of wild type V. cholerae and that fatty acid supplementation can rescue this inhibition. In an AasS deletion strain, supplementation with cerulenin and fatty acids allows for growth showcasing the redundancy of environmental fatty acid utilization in V. cholerae."

Journal • Cholera • FASN

Changes in microbial and metabolic profiles of mice fed with long-term high salt diet. (PubMed, BMC Gastroenterol) - "Long-term HSD affects physiological traits, alters gut metabolites profiles, and impacts the composition and function of gut microbiota, thus causes a certain impact on lipid metabolism."

Journal • Preclinical • Metabolic Disorders • FGF21

Cerulenin Partially Corrects the Disrupted Developmental Transcriptomic Signature in Huntington's Disease Striatal Medium Spiny Neurons. (PubMed, Stem Cells) - "We pinpointed numerous small molecules with known benefits in HD models and previously untested novel molecules. A top candidate, Cerulenin, partially restored the DARPP-32 levels and electrical activity in HD MSNs, and also modulated genes involved in multiple HD-related pathways."

Journal • CNS Disorders • Huntington's Disease • Movement Disorders

High-Throughput Screening to Identify Novel Compounds Affecting the Genome Editing Efficiency of CRISPR System. (PubMed, Molecules) - "After two rounds of screening, we identified that CP-724714, a ErbB2 (HER2) tyrosine kinase inhibitor, decreased the CRISPR/Cas9 efficiency and reduced the off-target effects by suppressing the efficiency of CRISPR/Cas9, and was thus named a CRISPR decelerator (or inhibitor), while Clofarabine, a DNA synthesis inhibitor, increased the efficiency of CRISPR/Cas9, and was named a CRISPR accelerator. Among them, Tranilast, Cerulenin and Rosolic acid are potential SSA decelerators, while Resveratrol is a potential SSA accelerator. These identified compounds may be useful in optimizing mammalian genetic manipulation techniques."

Journal • Gene Therapies • Genetic Disorders • HER-2

Fatty acid synthase inhibitor cerulenin attenuates glioblastoma progression by reducing EMT and stemness phenotypes, inducing oxidative and ER stress response, and targeting PI3K/AKT/NF-κB axis. (PubMed, Med Oncol) - "The results demonstrated for the first time that inhibiting FA production and FASN function induces cell death through ROS generation and ER stress while simultaneously reducing the motility and aggressiveness of U-87MG human glioblastoma cells by attenuating EMT and stemness phenotypes. Therefore, blocking lipid metabolism using CER may be considered as a good candidate for GB therapeutic option."

Journal • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Metabolic Disorders • Oncology • Solid Tumor • FASN • HSF1

Breeding High-Yield Ethyl Caproate-Producing Saccharomyces cerevisiae in Sake: Flux Regulation from Glycolytic Fermentation to the FAS Pathway and Alcohol Acyltransferase Overexpression. (PubMed, J Agric Food Chem) - "Subsequently, the cerulenin-resistant mutant strain YH-2-34, after 15 passages of adaptive domestication, produced 4.13 times more caproic acid than the wild type...By regulating the flux from glycolytic fermentation to the FAS pathway and overexpressing AAT, we constructed a high-yield ethyl-caproate-producing Saccharomyces cerevisiae strain. This may bring practical transformations to traditional brewing industries."

Journal

A Genetically Encoded Fluorescent Biosensor for Intracellular Measurement of Malonyl-CoA. (PubMed, ACS Bio Med Chem Au) - "In HeLa cells, we used Malibu to monitor the impact of fatty acid biosynthesis inhibition on malonyl-CoA dynamics in single cells, finding that two inhibitors of fatty acid biosynthesis, cerulenin and orlistat, which inhibit different steps of fatty acid biosynthesis, increase malonyl-CoA levels. Altogether, we have developed a new genetically encoded biosensor for malonyl-CoA, which can be used to study malonyl-CoA dynamics in single cells, providing an unparalleled view into fatty acid biosynthesis."

Journal

Oral Fusobacterium nucleatum resists the acidic pH of the stomach due to membrane erucic acid synthesized via enoyl-CoA hydratase-related protein FnFabM. (PubMed, J Oral Microbiol) - "Inhibition of FnFabM expression by cerulenin reduced the C22:1(n9) content and decreased the colonization efficiency of F. nucleatum in the stomach and jejunum of mice. Oral F. nucleatum translocate to the intestine by resisting the acidic environment owing to the presence of erucic acid in its cell membrane, which is regulated by FnFabM. These results provide novel insights into the mechanisms underlying the oral bacteria survival in acidic environments and their potential to colonize the intestine; thus, shedding light on the oral-gut axis and its implications on human health."

Journal • Gastrointestinal Disorder

Fatty Acid Synthase (FASN) Inhibitors Suppress Metformin-Induced Fat Accumulation and Apoptosis in H4IIE Hepatocellular Carcinoma Cells. (PubMed, Dev Reprod) - "However, the degree of suppressive effect of metformin on TG synthesis, apoptosis, and cell migration was much more prominent by the inhibition of AMPK by compound C than cerulenin. In conclusion, our study found that excess fat accumulation is responsible for the apoptosis of H4IIE HCC cells and is informative for designing anti-tumor reagents, especially in HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • AMPK • FASN

DOWN-REGULATION OF FATTY ACID SYNTHASE (FASN) AND UPREGULATION OF CHOLESTEROL 25-HYDROXYLASE AS A MEANS OF IMPEDING MPOX INFECTION. (WRMC 2025) - "To identify the potential cytotoxic effect of the compounds used to block infection with MPXV, the 50% cytotoxic concentration (CC50) was evaluated by treating Huh 7.5 or Hela cells with increasing doses of C75, Cerulenin, and 25HC for 24 hours...The expression of FASN began declining at 1 HPI and this trend became more significant at 3 and 6 HPI. On the other hand, CH25H was significantly increased during MPXV infection."

Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases • DDX58 • FAS • FASN • IFIT1 • IL6 • IRF1

Engineering an Escherichia coli strain for enhanced production of flavonoids derived from pinocembrin. (PubMed, Microb Cell Fact) - "Through the integration of microbial chassis engineering and screening of enzyme candidates, we considerably increased the production levels of microbially synthesised pinocembrin, chrysin, pinostrobin, pinobanksin, and galangin. With the introduction of additional chassis modifications geared towards improving cofactor supply and regeneration, as well as alleviating potential toxic effects of intermediates and end products, we anticipate further enhancements in the yields of these pinocembrin derivatives, potentially enabling greater diversification in microbial hosts."

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