MAPSI (Management and Analysis for Polyketide Synthase Type I) has been developed to offer computational analysis methods to detect type I PKS (polyketide synthase) gene clusters in genome sequences. MAPSI provides a genome analysis component, which detects PKS gene clusters by identifying domains in proteins of a genome. MAPSI also contains databases on polyketides and genome annotation data, as well as analytic components such as new PKS assembly and domain analysis. The polyketide data and analysis component are accessible through Web interfaces and are displayed with diverse information. MAPSI, which was developed to aid researchers studying type I polyketides, provides diverse components to access and analyze polyketide information and should become a very powerful computational tool for polyketide research. The system can be extended through further studies of factors related to the biological activities of polyketides.
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http://dx.doi.org/10.4014/jmb.0809.554 | DOI Listing |
While engineering modular polyketide synthases (PKSs) using the recently updated module boundary has yielded libraries of triketide-pentaketides, this strategy has not yet been applied to the combinatorial biosynthesis of macrolactones or macrolide antibiotics. We developed a 2-plasmid system for the construction and expression of PKSs and employed it to obtain a refactored pikromycin synthase in that produces 85 mg of narbonolide per liter of culture. The replacement, insertion, deletion, and mutagenesis of modules enabled access to hexaketide, heptaketide, and octaketide derivatives.
View Article and Find Full Text PDFFEBS Lett
January 2025
Department of Chemistry, Tokyo Institute of Technology (Institute of Science Tokyo), Japan.
Modular polyketide synthases (PKSs) are multi-domain enzymes involved in the biosynthesis of polyketide natural products. The dehydratase (DH) domain catalyzes the dehydration of the β-hydroxyacyl unit attached to the acyl carrier protein (ACP) domain in modular PKS. Although the DH domain likely recognizes the cognate ACP domain during the dehydration reaction, the molecular basis of DH-ACP interactions remains elusive.
View Article and Find Full Text PDFMicroorganisms
January 2025
Department of Molecular Biology, Faculty of Biology, University of Plovdiv, Tzar Assen 24, 4000 Plovdiv, Bulgaria.
Lactobacillus is a key genus of probiotics commonly utilized for the treatment of oral infections The primary aim of our research was to investigate the probiotic potential of the newly isolated DPL5 strain from human breast milk, focusing on its ability to combat biofilm-forming pathogens such as . Employing in vitro approaches, we demonstrate DPL5's ability to endure at pH 3 with survival rates above 30%, and withstand the osmotic stress often found during industrial processes like fermentation and freeze drying, retaining over 90% viability. The lyophilized cell-free supernatant of DPL5 had a significant antagonistic effect against biofilm-producing nasal strains of , and it completely eradicated biofilms at subinhibitory concentrations of 20 mg·mL.
View Article and Find Full Text PDFClin Transl Med
February 2025
Synthetic Biology of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), PharmaScienceHub (PSH), Saarbrücken, Germany.
The eXchange Unit between Thiolation domains approach and artificial intelligence (AI)-driven tools like Synthetic Intelligence are transforming nonribosomal peptide synthetase and polyketide synthase engineering, enabling the creation of novel bioactive compounds that address critical challenges like antibiotic resistance and cancer. These innovations expand chemical space and optimize biosynthetic pathways, offering precise and scalable therapeutic solutions. Collaboration across synthetic biology, AI, and clinical research is essential to translating these breakthroughs into next-generation treatments and revolutionizing drug discovery and patient care.
View Article and Find Full Text PDFMar Drugs
January 2025
Key Laboratory of Chemical Biology (Ministry of Education), Shandong Basic Science Research Center (Pharmacy), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation and identification of four classes of secondary metabolites from wild-type SDU050, alongside five additional metabolite classes, including three novel cytochalasins (-), obtained from a mutant strain through the metabolic blockade strategy.
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