A cDNA clone (named ), which shows high homology to the known chalcone synthase (CHS)-like type III PKS, was obtained from the leaves of . The PnPKS protein with ferulic acid catalyzed lactonization instead of chalcone or stilbene formation. The new product was characterized as a styrylpyrone, 11-methoxy-bisnoryangonin, which is the lactonization compound of a linear triketide formed as the reaction product of PnPKS protein with ferulic acid. These results show that encodes a styrylpyrone synthase (SPS)-like PKS that catalyzes two-chain elongation with feruloyl CoA-linked starter substrates. Although these styrylpyrone compounds are promising for use in human healthcare, they are mainly obtained by extraction from raw plant or mushroom sources. For synthesis of 11-methoxy-bisnoryangonin in the heterologous host from a simple sugar as a starter, the artificial biosynthetic pathway contained five genes: , , , and , along with the gene. The engineered -tyrosine overproducing ∆COS1 strain, in which five biosynthetic genes were cloned into two vectors, pET-opT5M and pET22-4P, was cultured for 24 h in a minimal glucose medium containing ampicillin and kanamycin. As a result, 11-methoxy-bisnoryangonin production of up to 52.8 mg/L was achieved, which is approximately 8.5-fold higher than that in the parental strain harboring a plasmid for 11-methoxy-bisnoryangonin biosynthesis. As a potential styrylpyrone compound, 11-methoxy-bisnoryangonin, was successfully produced in from a simple glucose medium, and its production titer was also increased using engineered strains. This study provides a useful reference for establishing the biological manufacture of styrylpyrone compounds.
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http://dx.doi.org/10.3389/fmicb.2021.714335 | DOI Listing |
J Comput Chem
January 2025
Department of Organic Chemistry, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.
Lipophilicity and acidity/basicity are fundamental physical properties that profoundly affect the compound's pharmacological activity, bioavailability, metabolism, and toxicity. Predicting lipophilicity, measured by (1-octanol-water distribution coefficient logarithm), and acidity/basicity, measured by (negative of acid ionization constant logarithm), is essential for early drug discovery success. However, the limited availability of experimental data and poor accuracy of standard and assessment methods for saturated fluorine-containing derivatives pose a significant challenge to achieving satisfactory results for this compound class.
View Article and Find Full Text PDFJ Drug Deliv Sci Technol
February 2025
Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY, 40202.
Whether it be due to genetic variances, lack of patient adherence, or sub-optimal drug metabolism, the risk of antibiotic resistance from medications administered systemically continues to pose significant challenges to fighting infectious diseases. Ideally, infections would be treated locally for maximal efficacy while minimizing off-target effects. The electrospinning of biomaterials has recently facilitated the creation of electrospun nanofibers as an alternative delivery vehicle for local treatment.
View Article and Find Full Text PDFBrief Bioinform
November 2024
College of Computer Science and Electronic Engineering, Hunan University, Changsha 410082, China.
The role of cell-cell communications (CCCs) is increasingly recognized as being important to differentiation, invasion, metastasis, and drug resistance in tumoral tissues. Developing CCC inference methods using traditional experimental methods are time-consuming, labor-intensive, cannot handle large amounts of data. To facilitate inference of CCCs, we proposed a computational framework, called CellMsg, which involves two primary steps: identifying ligand-receptor interactions (LRIs) and measuring the strength of LRIs-mediated CCCs.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Center for Advanced Innate Cell Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15).
View Article and Find Full Text PDFJ Inorg Biochem
January 2025
Yusuf Hamied Department of Chemistry, Lensfield Rd, Cambridge CB2 1EW, UK.
By introducing new-to-nature transformations, artificial metalloenzymes hold great potential for expanding the biosynthetic toolbox. The chemistry of an active cofactor in these enzymes is highly dependent on how the holoprotein is assembled, potentially limiting the choice of organometallic complexes amenable to incorporation and ability of the protein structure to influence the metal centre. We have previously reported a method utilising ligand exchange as a means to introduce ruthenium-arene fragments into a four-helix bundle protein.
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