title: Submerged conidiation and product formation by Aspergillus niger at low specific growth rates are affected in aerial developmental mutants.
abstract: Exposure to an aerial environment or severe nutrient limitation induces asexual differentiation in filamentous fungi. Submerged cultivation of Aspergillus niger in carbon- and energy-limited retentostat cultures both induces and fuels conidiation. Physiological and transcriptomic analyses have revealed that this differentiation strongly affects product formation. Since conidiation is inherent in the aerial environment, we hypothesized that product formation near zero growth can be influenced by affecting differentiation or development of aerial hyphae in general. To investigate this idea, three developmental mutants (ΔfwnA, scl-1, and scl-2 mutants) that have no apparent vegetative growth defects were cultured in maltose-limited retentostat cultures. The secondary-metabolite profile of the wild-type strain defined flavasperone, aurasperone B, tensidol B, and two so far uncharacterized compounds as associated with conidium formation, while fumonisins B(2), B(4), and B(6) were characteristic of early response to nutrient limitation by the vegetative mycelium. The developmental mutants responded differently to the severe substrate limitation, which resulted in distinct profiles of growth and product formation. fwnA encodes the polyketide synthase responsible for melanin biosynthesis during aerial differentiation, and we show that conidial melanin synthesis in submerged retentostat cultures and aurasperone B production are fwnA dependent. The scl-1 and scl-2 strains are two UV mutants generated in the ΔfwnA background that displayed reduced asexual conidiation and formed sclerotium-like structures on agar plates. The reduced conidiation phenotypes of the scl-1 and scl-2 strains are reflected in the retentostat cultivation and are accompanied by elimination or severely reduced accumulation of secondary metabolites and distinctly enhanced accumulation of extracellular protein. This investigation shows that submerged conidiation and product formation of a mitosporic fungus cultured at low specific growth rates can be fundamentally affected by interfering with the genetic program for differentiation of aerial hyphae, opening new perspectives for tailoring industrial performance.
authors.affiliation: Institute of Biology Leiden, P.O. Box 9505, 2300 RA Leiden, The Netherlands.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Jørgensen
authors.forename: Kristian F
authors.initials: KF
authors.lastname: Nielsen
authors.forename: Mark
authors.initials: M
authors.lastname: Arentshorst
authors.forename: Joohae
authors.initials: J
authors.lastname: Park
authors.forename: Cees A
authors.initials: CA
authors.lastname: van den Hondel
authors.forename: Jens C
authors.initials: JC
authors.lastname: Frisvad
authors.forename: Arthur F
authors.initials: AF
authors.lastname: Ram
mesh_terms: D001234:Aspergillus niger / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D002867:Chromones; D003470:Culture Media; D004781:Environmental Exposure; D037341:Fumonisins; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005663:Furans; D020869:Gene Expression Profiling; D005800:Genes, Fungal; D025301:Hyphae / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D011758:Pyrroles; D012100:Reproduction, Asexual / Q000235:genetics; D013172:Spores, Fungal / Q000235:genetics* / Q000378:metabolism*; D013217:Starvation; D013312:Stress, Physiological
chemical_list: D002867:Chromones; D003470:Culture Media; D037341:Fumonisins; D005656:Fungal Proteins; D005663:Furans; D011758:Pyrroles; C535085:flavasperone; C515288:tensidol B