Using a systems biology approach to improve filamentous fungal fermentation

Filamentous fungi are used in bioprocess-industry fermentations to produce billions of dollars in beneficial products annually. During fungal fermentation, mycelial morphology, the fungal cell wall, and its material properties all play a critical role. Yet relatively little is known about how regulatory mechanisms, or downstream effectors, impact morphological development, cell wall material properties or related processes such as protein secretion. Early work in our lab showed creative feeding schemes (i.e., intermittent addition of limiting nutrient) could be used to alter fungal morphology and increase productivity. Since then, we have been using a systems biology approach to better understand the molecular basis for this phenomena and have focused our research on cell-wall synthesis, its regulation, its impact on morphological development and protein secretion. For example, we are studying Aspergillus nidulans deletion stains, lacking putative cell-wall related genes, using a sophisticated set of experimental tools to assess subsequent phenotypes and develop insight regarding gene function. Proteomic analysis, of both cytoplasmic and cell-wall protein fractions, shows these gene deletions affect a wide range of cellular processes. And phosphoproteomic analysis is helping us understand gene regulation related to cell wall repair. To study protein secretion, we have generated thousands of mutants and have sequenced the 50 most interesting to connect genetic changes to altered protein secretion. Details related to these projects will be discussed.