Recent advances in the genome mining of Aspergillus secondary metabolites (covering 2012-2018)

Abstract

Secondary metabolites (SMs) produced by filamentous fungi possess diverse bioactivities that make them excellent drug candidates. Whole genome sequencing has revealed that fungi have the capacity to produce a far greater number of SMs than have been isolated, since many of the genes involved in SM biosynthesis are either silent or expressed at very low levels in standard laboratory conditions. There has been significant effort to activate SM biosynthetic genes and link them to their downstream products, as the SMs produced by these "cryptic" pathways offer a promising source for new drug discovery. Further, an understanding of the genes involved in SM biosynthesis facilitates product yield optimization of first-generation molecules and genetic engineering of second-generation analogs. This review covers advances made in genome mining SMs produced by Aspergillus nidulans, Aspergillus fumigatus, Aspergillus niger, and Aspergillus terreus in the past six years (2012-2018). Genetic identification and molecular characterization of SM biosynthetic gene clusters, along with proposed biosynthetic pathways, will be discussed in depth.

Scheme 1. Biosynthesis of ent-pimara-8(14),15-diene in A. nidulans.

Scheme 2. Biosynthesis of asperniduglene A1 in A. nidulans.

Scheme 3. Biosynthesis of aspernidine A in A. nidulans.

Scheme 4. Biosynthesis of microperfuranone in A. nidulans.

Scheme 5. Biosynthesis of fellutamide B in A. nidulans.

Scheme 6. Biosynthesis of cichorine in A. nidulans.

Scheme 7. Biosynthesis of aspercryptin in A. nidulans.

Scheme 8. Biosynthesis of felinone A in A. nidulans.

Scheme 9. Biosynthesis of 4′-methoxyviridicatin in A. nidulans.

Scheme 10. Biosynthesis of grey-brown conidiophore pigment in A. nidulans.,

Scheme 11. Biosynthesis of (+)-asperlin in A. nidulans.

Scheme 12. Biosynthesis of hexadehydroastechrome in A. fumigatus.

Scheme 13. Biosynthesis of endocrocin in A. fumigatus.

Scheme 14. Biosynthesis of trypacidin in A. fumigatus.

Scheme 15. Biosynthesis of helvolic acid in A. fumigatus.

Scheme 16. Biosynthesis of fumipyrrole in A. fumigatus.

Scheme 17. Biosynthesis of neosartoricin and fumicyclines in A. fumigatus.,

Scheme 18. Biosynthesis of fumagillin in A. fumigatus.

Scheme 19. Biosynthesis of kotanin in A. niger.

Scheme 20. Biosynthesis of azanigerones in A. niger.

Scheme 21. Biosynthesis of yanuthone D in A. niger.

Scheme 22. Biosynthesis of pyranonigrins E–J in A. niger.,

Scheme 23. Biosynthesis of pyranonigrin A in A. niger.

Scheme 24. Biosynthesis of aspterric acid in A. terreus.

Scheme 25. Biosynthesis of phenguignardic acid in A. terreus.

Scheme 26. Biosynthesis of asperphenamate in A. terreus.

Scheme 27. Biosynthesis of citreoviridin in A. terreus.

Jillian Romsdahl

Clay C. C. Wang