Inducing secondary metabolite production of Aspergillus sydowii through microbial co-culture with Bacillus subtilis

Abstract

Background The co-culture strategy which mimics natural ecology by constructing an artificial microbial community is a useful tool to activate the biosynthetic gene clusters to generate new metabolites. However, the conventional method to study the co-culture is to isolate and purify compounds separated by HPLC, which is inefficient and time-consuming. Furthermore, the overall changes in the metabolite profile cannot be well characterized. Results A new approach which integrates computational programs, MS-DIAL, MS-FINDER and web-based tools including GNPS and MetaboAnalyst, was developed to analyze and identify the metabolites of the co-culture of Aspergillus sydowii and Bacillus subtilis. A total of 25 newly biosynthesized metabolites were detected only in co-culture. The structures of the newly synthesized metabolites were elucidated, four of which were identified as novel compounds by the new approach. The accuracy of the new approach was confirmed by purification and NMR data analysis of 7 newly biosynthesized metabolites. The bioassay of newly synthesized metabolites showed that four of the compounds exhibited different degrees of PTP1b inhibitory activity, and compound N2 had the strongest inhibition activity with an IC50 value of 7.967 μM. Conclusions Co-culture led to global changes of the metabolite profile and is an effective way to induce the biosynthesis of novel natural products. The new approach in this study is one of the effective and relatively accurate methods to characterize the changes of metabolite profiles and to identify novel compounds in co-culture systems.

Bioactive compounds and biomedical applications of endophytic fungi: a recent review

“…Co-culturing in this case is between different microorganism (fungi and bacteria) in the same medium. Sun et al [ 151 ] carried out co-culture between Aspergillus sydowii and Bacillus subtilis , and found seven new compounds which possess biological activities. Akone et al [ 152 ] reported that, co-culturing of endophytic Chaetomium sp.…”

Ameliorating Effect of the Total Flavonoids of Morus nigra L. on Prediabetic Mice Based on Regulation of Inflammation and Insulin Sensitization

“…To investigate the main components in the TFM, the data of high-performance liquid chromatography (HPLC) and high-resolution LC–MS/MS were imported into MS-DIAL and MS-FINDER software, an assay integrating the computational programs. The software combination provided higher prediction accuracy than the traditional LC–MS/MS analysis, which has been validated in our previously study . A total of 30 compositions were identified and are listed in Table .…”

Marine natural products

“…160 Co-culture of A. sydowii wth the bacterium Bacillus subtilis induced production of 25 known and new metabolites by the fungus including serine sydonate 345 and an isomer of macrolactin U 346. 161 Furanaspermeroterpenes A 347 and B 348, meroterpenoids with an unique 6/6/ 6/5/5 pentacyclic skeleton were isolated from a gastropodderived Aspergillus terreus strain, along with ve further meroterpenes 349-353. 162 An OSMAC approach was utilised in the isolation of phenolic derivatives 354 and 355 from two separate Aspergillus strains and a known synthetic derivative 356 was obtained as a new MNP from the latter strain also.…”

“…160 Co-culture of A. sydowii wth the bacterium Bacillus subtilis induced production of 25 known and new metabolites by the fungus including serine sydonate 345 and an isomer of macrolactin U 346 . 161 Furanaspermeroterpenes A 347 and B 348 , meroterpenoids with an unique 6/6/6/5/5 pentacyclic skeleton were isolated from a gastropod-derived Aspergillus terreus strain, along with five further meroterpenes 349–353 . 162…”