Molecular Genetic Mining of the Aspergillus Secondary Metabolome: Discovery of the Emericellamide Biosynthetic Pathway

Abstract

The recently sequenced genomes of several Aspergillus species have revealed that these organisms have the potential to produce a surprisingly large range of natural products, many of which are currently unknown. We have found that A. nidulans produces emericellamide A, an antibiotic compound of mixed origins with polyketide and amino acid building blocks. Additionally, we describe the discovery of four previously unidentified, related compounds that we designate emericellamide C-F. Using recently developed gene targeting techniques, we have identified the genes involved in emericellamide biosynthesis. The emericellamide gene cluster contains one polyketide synthase and one nonribosomal peptide synthetase. From the sequences of the genes, we are able to deduce a biosynthetic pathway for the emericellamides. The identification of this biosynthetic pathway opens the door to engineering novel analogs of this structurally complex metabolite.

Diversity and biofilm inhibition activities of algicolous fungi collected from two remote islands of the Philippine archipelago

“…These compounds were previously isolated from marine-derived Aspergillus spp. (Chiang et al 2008, Deng et al 2013, Martín-Rodríguez et al 2014.…”

Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation

“…Recent data further complicate a serious estimation because communication occurs between gene clusters, which could potentially lead to even more compounds (5). A major hurdle to identifying this untapped reservoir, however, is the observation that most of these gene clusters are silent under standard laboratory conditions (6)(7)(8). To address this problem, methods were established to activate silent gene clusters by genetic engineering (6,7,9).…”

The antibiotic resistance crisis, with a focus on the United States

“…Sequencing of the A. nidulans genome revealed 27 polyketide synthases and 14 non-ribosomal peptide synthases, whereas previously less than 10 biosynthetic gene clusters had been known. 64 Genome mining involves powerful techniques for discovery of new natural products. 65 In recent years, a number of additional 'silent' secondary metabolites have been found by genome mining.…”