A gene cluster encoding a nonribosomal peptide synthetase-like enzyme catalyzes γ-aromatic butenolides

Abstract

Sea cucumber-derived fungi have attracted much attention due to their capacity to produce an incredible variety of secondary metabolites. Genome-wide information on Aspergillus micronesiensis H39 obtained using third-generation sequencing technology (PacBio-SMRT) showed that the strain contains nonribosomal peptide synthetase (NRPS)-like gene clusters, which aroused our interest in mining its secondary metabolites. 11 known compounds (1–11), including two γ-aromatic butenolides (γ-AB) and five cytochalasans, were isolated from A. micronesiensis H39. The structures of the compounds were determined by NMR and ESIMS, and comparison with those reported in the literature. From the perspective of biogenetic origins, the γ-butyrolactone core of compounds 1 and 2 was assembled by NRPS-like enzyme. All of the obtained compounds showed no inhibitory activity against drug-resistant bacteria and fungi, as well as compounds 1 and 2 had no anti-angiogenic activity against zebrafish.

Keywords:

• Aspergillus micronesiensis
• sea cucumber
• butyrolactone
• cytochalasan
• bioactivity

Acknowledgements

The authors acknowledge the State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was funded by Key R&D Program of Shandong Province (2022SFGC0105), Innovation and Development Joint Fund of Natural Science Foundation from Shandong Province (ZR2021LSW022), Exploration Innovation Team (2021GXRC062), Jinan Talent Project for Universities (202228088), Young Taishan Scholarship to Xuekui Xia (tsqn202103100), Key innovation Project of Qilu University of Technology (Shandong Academy of Sciences) (2022JBZ01-06) and International cooperation Project of Qilu University of Technology (Shandong Academy of Sciences) (2022GH024), Key innovation Project and Science, Education and Industry Integration Innovation Pilot Project Qilu University of Technology (Shandong Academy of Sciences) (2022PX051, 2022PX027), Natural Science Foundation from Shandong Province (ZR2022QC186).