Ochratoxin A (OTA) is a well-known mycotoxin with wide distribution in food and feed. Fungal genome sequencing has great utility for identifying secondary metabolites gene clusters for known and novel compounds. A comparative analysis of the OTA-biosynthetic cluster in , and has revealed a high synteny in OTA cluster organization in five structural genes (, , , and ). Moreover, a recent detailed comparative genome analysis of Aspergilli OTA producers led to the identification of a cyclase gene, , located in the OTA cluster between the and genes, encoding for a predicted protein with high similarity to SnoaLs domain. These proteins have been shown to catalyze ring closure steps in the biosynthesis of polyketide antibiotics produced in . In the present study, we demonstrated an upregulation of the cyclase gene in under OTA permissive conditions, consistent with the expression trends of the other OTA cluster genes and their role in OTA biosynthesis by complete gene deletion. Our results pointed out the involvement of a cyclase gene in OTA biosynthetic pathway for the first time. They represent a step forward in the understanding of the molecular basis of OTA biosynthesis in .
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http://dx.doi.org/10.3390/toxins13120892 | DOI Listing |
Elife
January 2025
Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, United States.
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.
View Article and Find Full Text PDFCommun Chem
January 2025
Graduate School of Engineering, Hokkaido University, N13-W8, Kita-ku, Sapporo, Hokkaido, 060-8628, Japan.
Lactacystin is an irreversible proteasome inhibitor isolated from Streptomyces lactacystinicus. Despite its importance for its biological activity, the biosynthesis of lactacystin remains unknown. In this study, we identified the lactacystin biosynthetic gene cluster by gene disruption and heterologous expression experiments.
View Article and Find Full Text PDFBiofilm
June 2025
State Key Laboratory of Marine Resource Utilization in the South China Sea, Hainan University, Haikou, 570228, Hainan Province, China.
is a prevalent pathogen in both humans and marine species, exhibiting high adaptability to various adverse environmental conditions. Our previous studies have shown that Δ formed three enhanced biofilm types, including spectacular surface-attached biofilm (SB), scattered pellicle biofilm (PB), and colony rugosity. However, the precise mechanism through which regulates biofilm formation has remained unclear.
View Article and Find Full Text PDFBMC Cancer
January 2025
Department of Gynecology, East China Normal University Wuhu Affiliated Hospital (The Second People's Hospital of Wuhu City), Wuhu, 241000, China.
Objective: Neuroendocrine cervical carcinoma (NECC) is a rare but highly aggressive tumor. The clinical management of NECC follows neuroendocrine neoplasms and cervical cancer in general. However, the diagnosis and prognosis of NECC remain dismal.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
State Key Laboratory of Southwestern Chinese Medicine Resources, and Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, P. R. China.
A prolific multi-product sesterterpene synthase CbTPS1 is characterized from the medicinal Brassicaceae plant Capsella bursa-pastoris. Twenty different sesterterpenes including 16 undescribed compounds, possessing 10 different mono-/di-/tri-/tetra-/penta-carbocyclic skeletons, including the unique 15-membered macrocyclic and 24(15→14)-abeo-capbuane scaffolds, are isolated and structurally elucidated from engineered Escherichia coli strains expressing CbTPS1. Site-directed mutagenesis assisted by molecular dynamics simulations resulted in the variant L354M with up to 13.
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