cerulenin / Fermentek - LARVOL DELTA

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."

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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."

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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."

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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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A Genetically Encoded Fluorescent Biosensor for Intracellular Measurement of Malonyl-CoA. (PubMed, bioRxiv) - "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 sensitively study malonyl-CoA dynamics in single cells, providing an unparalleled view into fatty acid biosynthesis."

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Self-Resistance Gene-Guided Discovery of the Molecular Basis for Biosynthesis of the Fatty Acid Synthase Inhibitor Cerulenin. (PubMed, Angew Chem Int Ed Engl) - "Using in vitro assays, we further validated the roles of amidotransferase CerD in amidation, and oxidase CerF and reductase CerE in the final two-electron oxidation and enone reduction steps towards 1. These findings expand our understanding of complex tailoring modifications in highly reducing PKS pathways and pave the way for the engineered biosynthesis of cerulenin analogues."

Journal • Genetic Disorders • Obesity • Oncology • FASN

Fatty Acid Synthase Inhibitor Cerulenin Hinders Liver Cancer Stem Cell Properties through FASN/APP Axis as Novel Therapeutic Strategies. (PubMed, J Lipid Res) - "In addition, sorafenib, a multikinase inhibitor used as targeted therapy for advanced HCC, was employed in combination with cerulenin, demonstrating a great synergistic effect, particularly in CSCs. We found that APP plays a crucial role in CSCs' characteristics that can be inhibited by cerulenin. By focusing on FA metabolism, this study identified the FASN/APP axis as a viable target to develop a more potent therapy strategy for advanced HCC."

Cancer stem • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • FASN

Calcineurin activation improves cell survival during amino acid starvation in lipid droplet-deficient yeasts. (PubMed, Biochem Biophys Res Commun) - "This activation was inhibited by treatments that restore a normal endomembrane organization, i.e. inhibition of FA synthesis with cerulenin or deletion of the inhibitory transcription factor Opi1...An increase in intracellular calcium was observed in LD-deficient cells during AA starvation, but its inhibition by genetic deletion of MID1 or YVC1 did not affect calcineurin activity. In contrast, calcineurin activation required the direct regulator of calcineurin Rcn1 and its activating (GSK-3)-related protein kinase Mck1."

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The Inhibitory Effects of Maclurin on Fatty Acid Synthase and Adipocyte Differentiation. (PubMed, Int J Mol Sci) - "Using SwissDock software (ChEMBL version 23), we predicted protein interactions and demonstrated a high probability (95.6%) of maclurin targeting FAS, surpassing the interaction rates of established inhibitors like cerulenin...Furthermore, maclurin treatment resulted in significant reductions in lipid accumulation and the downregulated expression of critical adipogenic genes such as PPARγ, C/EBPα, and FAS, indicating the suppression of adipocyte differentiation. Maclurin shows potential as a novel FAS inhibitor with significant anti-adipogenic effects, offering a promising therapeutic avenue for the treatment and prevention of obesity."

Journal • Cardiovascular • Genetic Disorders • Metabolic Disorders • Obesity • FASN • PPARG

Optimizing Archaeal Lipid Biosynthesis in Escherichia coli. (PubMed, ACS Synth Biol) - "The archaeal phospholipids also served as a substrate for the E. coli cardiolipin synthase, resulting in archaeal and novel hybrid archaeal/bacterial cardiolipin species not seen in living organisms before. Growth of the E. coli strain with the mixed membrane shows an enhanced sensitivity to the inhibitor of fatty acid biosynthesis, cerulenin, indicating a critical dependence of the engineered E. coli strain on its native phospholipids."

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FAS Inhibited Proteomics and Phosphoproteomics Profiling of Colorectal Cancer Spheroids Shows Activation of Ferroptotic Death Mechanism. (PubMed, J Proteome Res) - "These results show that HT-29 spheroids exposed to cerulenin or TVB-2640 are undergoing a ferroptotic death mechanism. The data were deposited to the ProteomeXchange Consortium via the PRIDE repository with the identifier PXD050987."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Metabolic Disorders • Oncology • Solid Tumor • FASN

An inhibitory mechanism of AasS, an exogenous fatty acid scavenger: Implications for re-sensitization of FAS II antimicrobials. (PubMed, PLoS Pathog) - "A growing body of bacterial AasS-type isoenzymes compromises the clinical efficacy of FAS II-directed antimicrobials, like cerulenin...This facilitates the development of next-generation of anti-bacterial therapeutics, esp. the dual therapy consisting of C10-AMS scaffold derivatives combined with certain FAS II inhibitors."

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Cryptic Cerulenin Rearrangement in Ketosynthase Covalent Inhibition. (PubMed, J Am Chem Soc) - "Herein, we describe the use of stable isotopic tracking with NMR and MS methods to unravel the covalent mechanism of cerulenin against type II fatty acid ketosynthases. We detail the discovery of a unique C2-C3 retro-aldol bond cleavage and a structural rearrangement upon covalent inhibition of cerulenin at the active cysteine residue in E. coli type II fatty acid ketosynthases FabB and FabF."

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