Targeted Discovery of Sorbicillinoid Pigments with Anti-Inflammatory Activity from the Sponge-Derived Fungus Stagonospora sp. SYSU-MS7888 Using the PMG Strategy

Abstract

An effective identification and discovery of fungal pigments is very important to illustrate the role of fungal pigments in the life process and conduce to the discovery of new bioactive and edible pigments. The phenotype combined with metabolomic and genomic (PMG) strategy led to the discovery and characterization of three new sorbicillinoid pigments, stasorbicillinoids A–C (1–3), and five known analogues (4–8) from the sponge-derived fungus Stagonospora sp. SYSU-MS7888. Their structures were elucidated by the application of spectroscopic methods (NMR, MS, UV, IR, and ECD) and modified Mosher’s method. Compounds 1 and 2 featured novel naphthone nuclei linked by two alkyl side chains possibly undergoing inter- and intramolecular Michael reactions. Compounds 1–8 exhibited potent anti-inflammatory activity with IC50 values in the range of 3.56–22.8 μM. Furthermore, compound 2 inhibited the production of IL-1β, IL-6, and TNF-α in a dose-dependent manner. This study provides an effective strategy to accelerate the discovery of new fungal pigments and further exploration of their potential applications in different fields such as medicine and food industries.

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

“….59,21.81, 19.79, 18.89. The NMR data of compound 5 were consistent with the literature data 9. Compound 6: UV λmax (MeOH) 197, 298, 383 nm; HR-ESIMS m/z: 495.2027 [M − H] − (calcd for C 28 H 31 O 8 , 495.2024); 1 H NMR (600 MHz, DMSO-d 6 ): δ 7.23 (dd, J…”

“…SYSU-MS7888 was sequenced by secondgeneration sequencing, and antiSMASH analysis of the sequenced genome suggested that cluster 320.1 encodes a BGC (sta cluster) that shares significant similarity with the sorbicillinoid BGCs from T. reesei QM6a and P. chrysogenum. 9,20,21 (Figure 2). Cluster 320.1 harbors a pair of PKSs, a hr-PKS (StaC) and a nr-PKS (StaB), which are presumably responsible for the formation of sorbicillin monomer (1).…”

“…SYSU-MS7888. 9 Due to the highly complex cyclic scaffold and unique biological activities, 3,10 much research regarding the total synthesis, 11−13 biosynthesis, 14,15 and biological activities 4 of sorbicillinoids has been conducted. 16,17 The biosynthetic gene cluster (BGC) of sorbicillinoids from Penicillium chrysogenum was first identified by the Cox group, 10 and they showed that a pair of multifunctional fungal polyketide synthases (PKSs), SorA and SorB, are responsible for constructing the sorbicillinoid backbone sorbicillin (1) (Figure 1).…”

“…Sorbicillinoids are common fungal pigments produced by many terrestrial − and marine fungi. − Recently, our group developed a PMG (phenotype combined with metabolomic and genomic) strategy to isolate novel fungal pigments and successfully identified several sorbicillinoid pigments from the sponge-derived fungus Stagonospora sp. SYSU-MS7888 . Due to the highly complex cyclic scaffold and unique biological activities, , much research regarding the total synthesis, − biosynthesis, , and biological activities of sorbicillinoids has been conducted. , The biosynthetic gene cluster (BGC) of sorbicillinoids from Penicillium chrysogenum was first identified by the Cox group, and they showed that a pair of multifunctional fungal polyketide synthases (PKSs), SorA and SorB, are responsible for constructing the sorbicillinoid backbone sorbicillin ( 1 ) (Figure ).…”

Integrating Genomics and Metabolomics for the Targeted Discovery of New Cyclopeptides with Antifungal Activity from a Marine-Derived Fungus Beauveria felina

“…Marine fungi are known to produce a wide range of active substances with biomedical and agricultural values. , As part of our ongoing search for bioactive molecules from marine fungi, − we obtained the fungus Beauveria felina SYSU-MS7908, which showed an antagonistic effect on G. citri-aurantii.…”