Aspergillolide, a new 12-membered macrolide from sea cucumber-derived fungus Aspergillus sp. S-3-75

Abstract A new 12-membered macrolide, aspergillolide (1), along with nine known compounds (2–10), were isolated from the fungus Aspergillus sp. S-3-75 associated with the sea cucumber Holothuria nobilis Selenka. The structure and absolute stereochemistry of 1 were elucidated on the basis of extensive spectroscopic methods and single crystal X-ray diffraction analysis. Graphical Abstract


Introduction
Marine-derived Aspergillus genus fungi are widely recognised as prolific sources of biologically active and structurally unique secondary metabolites. Up to mid-2010, over 500 new secondary metabolites were reported from marine Aspergillus fungi, and about 36% of the metabolites have various biological activities, such as cytotoxic, antibacterial, free radical scavenging, anti-parasitic, antiviral and antiproliferative activities, etc., (Chen et al. 2014;Rateb and Ebel 2011;Xu et al. 2017;Zhao et al. 2016).
The immunosuppressive effects of compounds 1-9 were examined on splenocyte proliferation induced by concanavalin A (ConA). The results showed that these compounds have no significant immunosuppressive effects at concentrations 10 lmol, 1.0 lmol and 0.1 lmol.

Fungal strain
The fungus was isolated from the intestine of sea cucumber at 44.42 W, 60.54 S in the Antarctic. It was isolated in glucose peptone yeast (GPY) medium with incubation at 28 C. Due to its 18S rDNA sequence, the strain was assigned to the genus Aspergillus. The strain was deposited in the PDA medium at the Naval Military University, 800 Xiangyin Road, 200433, Shanghai, China.

Antiproliferation assay
The immunosuppressive effects of compounds 1-9 were examined on splenocyte proliferation induced by concanavalin A (ConA) using a method described in the literature (Qiao et al. 2014;Zhang et al. 2015).

Conclusion
Ten metabolites including a new 12-membered macrolide aspergillolide (1) were firstly isolated from the fungus Aspergillus sp. S-3-75, which showed no immunosuppressive effects on splenocyte proliferation induced by ConA. Despite the lack of immunosuppressive effect for 1, some 12-membered macrolides structurally similar to 1 were reported to have phototoxic, cytotoxic, antifungal, antibacterial and antiviral activities (Sun et al. 2013). We believe that compound 1 and its potential derivatives in the fungus Aspergillus sp. S-3-75 deserve further study.