Major Facilitator Superfamily Transporter Participates in the Formation of Dimeric Sorbicillinoids Pigments

Ren, Shuya; Zeng, Yuping; Wang, Qiang; Lin, Qifeng; Yin, Xinjian; Chen, Senhua; Wang, Muhua; Liu, Lan; Gao, Zhizeng

doi:10.1021/acs.jafc.3c03004

Cited by 6 publications

(1 citation statement)

References 34 publications

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“…A recent study uncovered that the endoplasmic reticulum-located MFS StaE ( Stagonospora sp.) is involved in the formation of dimeric sorbicillinoids within sorD -lacking sor -like BGCs . Therefore, we conducted a bioinformatics comparison between StaE and our MFS, PciSorT, encoded by pcisor BGC.…”

Section: Resultsmentioning

confidence: 99%

Sorbremnoids A and B: NLRP3 Inflammasome Inhibitors Discovered from Spatially Restricted Crosstalk of Biosynthetic Pathways

Zhang,

Liu,

Jiang

et al. 2024

J. Am. Chem. Soc.

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Crosstalk-oriented chemical evolution of natural products (NPs) is an efficacious strategy for generating novel skeletons through coupling reactions between NP fragments. In this study, two NOD-like receptor protein 3 (NLRP3) inflammasome inhibitors, sorbremnoids A and B (1 and 2), with unprecedented chemical architectures were identified from a fungus Penicillium citrinum. Compounds 1 and 2 exemplify rare instances of hybrid NPs formed via a major facilitator superfamily (MFS)-like enzyme by coupling reactive intermediates from two separate biosynthetic gene clusters (BGCs), pcisor and pci56. Both sorbremnoids A and B are NLRP3 inflammasome inhibitors. Sorbremnoid A demonstrated strong inhibition of IL-1β by directly binding to the NLRP3 protein, inhibiting the assembly and activation of the NLRP3 inflammasome in vitro, with potential application in diabetic refractory wound healing through the suppression of excessive inflammatory responses. This research will inspire the development of anti-NLRP3 inflammasome agents as lead treatments and enhance knowledge pertaining to NPs derived from biosynthetic crosstalk.

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Section: Resultsmentioning

confidence: 99%

Sorbremnoids A and B: NLRP3 Inflammasome Inhibitors Discovered from Spatially Restricted Crosstalk of Biosynthetic Pathways

Zhang,

Liu,

Jiang

et al. 2024

J. Am. Chem. Soc.

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OSMAC Investigation Directed by Genome Information Led to the Discovery of Additional Five Types of Secondary Metabolites From Deep‐Sea Derived Penicillium Sp. SCSIO sof101

Wang,

Chen,

Yang

et al. 2024

Chemistry & Biodiversity

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Marine fungi are considered important resources for new lead compounds in One Strain Many Compounds (OSMAC) strategy. In particular, deep‐sea derived fungi have been deemed potent for novel bioactive structures due to their extreme living environment and evolution of special biosynthetic gene clusters (BGCs) for secondary metabolites. Chemical investigations of the deep‐sea derived Penicillium sp. SCSIO sof101 led to the discovery of 5 types of 21 bioactive compounds, including the significant anti‐Gram‐negative bacterial compound sulfoxanthicillin. Bioinformatics analysis of the strain revealed 56 BGCs for the secondary metabolites. This information guided the further culture optimization, which led to the discovery of another five types of secondary metabolites (1–11), including one non‐ribosomal peptide and polyketide (NRP–PK) type compounds (1–3), which included a new compound (1), one NRP type compounds (4–5), and three PK types compounds (6–11). The structure of compound 1 was elucidated by spectral analyses including HR‐ESI‐MS, 1D and 2D NMR, and chemical derivatization approaches. Compound 1 was inactive in the evaluation of antibacterial activity and cytotoxicity. Its biosynthetic pathway was proposed. This finding paves the way for further mining of OSMAC potent from the deep‐sea derived strain.

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Targeted isolation of sorbicilinoids from a deep-sea derived fungus with anti-neuroinflammatory activities

Wu,

Meng,

Liu

et al. 2024

Phytochemistry

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Major Facilitator Superfamily Transporter Participates in the Formation of Dimeric Sorbicillinoids Pigments

Cited by 6 publications

References 34 publications

Sorbremnoids A and B: NLRP3 Inflammasome Inhibitors Discovered from Spatially Restricted Crosstalk of Biosynthetic Pathways

Sorbremnoids A and B: NLRP3 Inflammasome Inhibitors Discovered from Spatially Restricted Crosstalk of Biosynthetic Pathways

OSMAC Investigation Directed by Genome Information Led to the Discovery of Additional Five Types of Secondary Metabolites From Deep‐Sea Derived Penicillium Sp. SCSIO sof101

Targeted isolation of sorbicilinoids from a deep-sea derived fungus with anti-neuroinflammatory activities

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