Differential expression of silent polyketide biosynthesis gene clusters in chemostat cultures of Aspergillus nidulans.
The genome of the fungal model organism Aspergillus nidulans harbors nearly 30 polyketide synthase genes, yet the majority of these genes remain silent in the absence of particular stimuli. In this study, environmental conditions such as low specific microbial growth rate as well as nitrate, orthophosphate and glucose limitations were simulated under a continuous cultivation regime to induce the expression of silent polyketide synthase genes. In addition to offline and online bioprocess parameters, the physiological equilibrium was defined at the transcript level in terms of indicator gene expression. The different cultivation parameters resulted in a differential expression of two polyketide synthase genes coding for the biosynthesis of a variety of phenolic compounds, such as orsellinic acid, lecanoric acid, emodins, chrysophanol, shamixanthone, and sanghaspirodin. Further investigation of the metabolome revealed the formation of a novel prenylated benzophenone derivative designated as pre-shamixanthone. Our data indicate that employing chemostat fermentations in combination with genome mining, transcriptome analysis and metabolic profiling represents a valuable approach for triggering cryptic biosynthetic pathways.
Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Beutenbergstrasse 11a, Jena, Germany.
Anindita
A
Sarkar
Alexander N
AN
Funk
Kirstin
K
Scherlach
Fabian
F
Horn
Volker
V
Schroeckh
Pranatchareeya
P
Chankhamjon
Martin
M
Westermann
Martin
M
Roth
Axel A
AA
Brakhage
Christian
C
Hertweck
Uwe
U
Horn
D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D001577:Benzophenones / Q000378:metabolism; D019149:Bioreactors / Q000382:microbiology*; D018929:Cell Culture Techniques; D020869:Gene Expression Profiling / Q000379:methods; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D055442:Metabolome / Q000235:genetics; D055432:Metabolomics / Q000379:methods; D005810:Multigene Family; D048630:Polyketide Synthases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism; D049490:Systems Biology; D059467:Transcriptome
D001577:Benzophenones; D061065:Polyketides; D048630:Polyketide Synthases