Aspergillus niger versus Aspergillus oryzae: Expression platforms for heterologous secondary metabolite production

E. Geiba and M. Brocka

Author address: 

aFungal Genetics and Biology, University of Nottingham, Nottingham, GB

Abstract: 

Filamentous fungi are treasure chests for novel secondary metabolites and genome mining has
uncovered a multitude of yet unexplored secondary metabolite biosynthesis gene clusters. Their
identification and characterisation is crucial for the development of drugs that combat various kinds of
diseases. Unfortunately, most of these gene clusters appear silent under laboratory cultivation conditions,
which requires heterologous gene expression in well-characterised expression systems. Previously, we
developed such an expression system in Aspergillus niger, which bases on regulatory elements from
the Aspergillus terreus terrein biosynthetic gene cluster. We used this platform to produce polyketides
(e.g. lecanoric acid), non-ribosomal peptide synthetase-like products (e.g. aspulvinone E) and
reconstituted the Asp-melanin biosynthesis pathway from A. terreus.
The latter studies led to an interest in understanding the chemistry of NRPS-like enzymes that produce
metabolites with antifungal, cytotoxic, antitumorigenic and antiviral activity. Enzymes of this class may
accept the same substrate, but form different products depending on their thioesterase domain. To study
these domains, we compared the aspulvinone E synthetase MelA from A. terreus with the atromentin
synthetase InvA5 from Paxillus involutus. While recombinant expression of melA in A. niger resulted in
aspulvinone E production, expression of invA5 led to a range of yet unknown products, but failed to
produce atromentin. In contrast, recombinant and purified InvA5 produced atromentin in vitro. We
therefore speculated that the physiology of A. niger might lead to a modification of the InvA5-derived
metabolite. Consequently, the expression system was transferred to the alternative host Aspergillus
oryzae. Indeed, A. oryzae produced aspulvinone E from MelA and, even more, atromentin from InvA5.
In conclusion, our recombinant expression system is perfectly suited for heterologous production of
secondary metabolites. However, the metabolic physiology of A. niger and A. oryzae differs and at least
two different expression platforms should be selected when aiming in the characterisation of novel
secondary metabolite biosynthesis genes.

2017

abstract No: 

19

Full conference title: 

The Fourteenth International Aspergillus Meeting, Asilomar Conference Center, Pacific Grove, CA, USA
    • Asperfest 14 (2017)