Sorbicillinoid Derivatives with the Radical Scavenging Activities from the Marine-Derived Fungus Acremonium chrysogenum C10

Abstract

Sorbicillinoids are a class of structurally diverse hexaketide metabolites with good biological activities. To explore new structural sorbicillinoids and their bioactivities, the marine-derived fungus Acremonium chrysogenum C10 was studied. Three new sorbicillinoid derivatives, acresorbicillinols A–C (1–3), along with five known ones, trichotetronine (4), trichodimerol (5), demethyltrichodimerol (6), trichopyrone (7) and oxosorbicillinol (8), were isolated. The structures of new sorbicillinoids were elucidated by analysis of nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS). The absolute configurations of compounds 1–3 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Compound 3 exhibited a strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, with the IC50 value ranging from 11.53 ± 1.53 to 60.29 ± 6.28 μM in 24 h. Additionally, compounds 2 and 3 showed moderate activities against Staphylococcus aureus and Cryptococcus neoformans, with IC50 values of 86.93 ± 1.72 and 69.06 ± 10.50 μM, respectively. The boundary of sorbicillinoid biosynthetic gene cluster in A. chrysogenum was confirmed by transcriptional analysis, and the biosynthetic pathway of compounds 1–8 was also proposed. In summary, our results indicated that A. chrysogenum is an important reservoir of sorbicillinoid derivatives, and compound 3 has the potential for new natural agents in DPPH radical scavenging.

Secondary Metabolites from Coral-Associated Fungi: Source, Chemistry and Bioactivities

“…A recent study indicated that sorbicillinoid derivatives from marine-derived fungus also possessed radical scavenging activities. In the last four years, 69 new sorbicillinoids were identified from fungi [ 155 , 156 ]. Dimethyl incisterol A3 ( 338 ) and (l7 R )-17-methylincisterol ( 339 ) were obtained from a soft coral-derived fungus Talaromyces sp.…”

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

“…Trichodimerol ( 5 ) is a unique cage-like dimeric sorbicillinoid with a bright yellow color. Trichodimerol has been frequently isolated from various fungi ,, and displays potent antitumor activities; , nevertheless, whether its formation is enzymatic or spontaneous is still subject to debate. We found that the sponge-derived fungus Stagonospora sp.…”

A Berberine Bridge Enzyme-like Oxidase Mediates the Cage-like Acresorbicillinol C Biosynthesis

“…14 Recently, three cage-like bisorbicillinoids, especially acresorbicillinol C (4) with strong DPPH radical scavenging activity, were isolated, and the sorbicillinoid biosynthetic gene cluster (Acsor BGC) was identified from Acremonium chrysogenum (Figure 2A). 18 Acsor BGC consists of two PKS genes (AcsorA and AcsorB) that are responsible for the backbone formation of sorbicillinoids. In addition, the cluster contains genes encoding an FMO (AcsorC), a BBE-like oxidase (AcsorD), a transporter (AcsorT), two regulators (AcsorR1 and AcsorR2), and one putative serine hydrolase (AcsorE).…”

“…To trace the origin of the oxygen atom in reactions catalyzed by AcsorC and AcsorD, we incubated 2a with AcsorC in 18 O 2saturated buffer, and the molecular weight of the generated 1 increased by 2 amu, indicating incorporation of 18 O into 1. When 1 was further incubated with AcsorD, the molecular weight of the generated 3 increased by 2 amu, suggesting no incorporation of 18 O into 3 from 1.…”

“…When 1 was further incubated with AcsorD, the molecular weight of the generated 3 increased by 2 amu, suggesting no incorporation of 18 O into 3 from 1. In contrast, almost no incorporation of 18 O into 1 was observed when 2a was incubated with AcsorC, and incorporation of 18 O into 3 when 1 was incubated with AcsorD in H 2 18O buffer (Figure S27). To identify the key amino acid residues and further reveal the catalytic mechanism of AcsorD, we developed a molecular docking model.…”