ABSTRACT
CONTENTS 11.1 Introduction .............................................................................................................................. 143 11.2 Uptake of Amino Acids in Aspergillus .................................................................................... 145
11.2.1 Aspergillus Amino Acid Uptake in Comparison to Other Fungi ............................... 145 11.2.2 Aspergillus Amino Acid Uptake Systems in Comparison to Mammalian
Counterparts ............................................................................................................... 147 11.3 Biosynthesis of Amino Acids in Aspergillus ........................................................................... 148
11.3.1 Sensing of the Intracellular Amino Acid Pool: Sensor Kinase CpcC and the TOR Pathway .......................................................................................................... 148
11.3.2 Cross-Pathway Control (CPC) System of Aspergillus ................................................ 151 11.3.2.1 Global Transcription Factor CpcA ............................................................... 151 11.3.2.2 Control of the CpcA-mRNA Amount .......................................................... 151 11.3.2.3 Transport of the Transcription Factor into the Nucleus ............................... 153 11.3.2.4 Ribosomal CpcB Component Represses Amino
Acid Biosynthesis ....................................................................................... 153 11.3.3 Examples for the Synthesis of Amino Acids and Derivatives ...................................... 153
11.3.3.1 Histidine Biosynthesis .................................................................................. 154 11.3.3.2 Lysine and Penicillin Biosynthesis of Aspergilli ......................................... 154 11.3.3.3 Aromatic Amino Acid and Terrequinone A Biosynthesis .......................... 155
11.4 Amino Acids Obtained by Protein Degradation in Aspergillus ............................................. 156 11.4.1 Prerequisites for Protein Degradation .......................................................................... 157 11.4.2 Ubiquitylation of Phosphorylated Substrates ............................................................... 160 11.4.3 Ubiquitin Ligases .......................................................................................................... 160 11.4.4 SCF Activity Is Controlled by Alternating Neddylation Status ................................... 162 11.4.5 PCI Complexes ............................................................................................................. 164
11.4.5.1 PCI and MPN Domain Proteins .................................................................. 164 11.4.5.2 COP9 Signalosome (CSN) .......................................................................... 166 11.4.5.3 Translation Initiation Factor 3 (eIF3). ......................................................... 166
11.5 Conclusion .................................................................................................................................. 166 Acknowledgments ................................................................................................................................. 168 References ............................................................................................................................................. 169
11.1 Introduction The aspergilli comprise a divergent and highly versatile group of fi lamentous fungi [1]. Among the over 185 aspergilli are several species with impact on human health, including 20 human pathogens. In addition, several economically, medically, and agriculturally important fungal species are part of the
Aspergillus family [1]. Bioactive molecules such as afl atoxins are secreted by Aspergillus fumigatus and Aspergillus fl avus [2-4]. Additionally, A. fumigatus is an important human pathogen causing invasive aspergillosis in immunocompromised patients [5]. Aspergillus oryzae and Aspergillus niger are of high importance to produce sake, miso, soy sauce, and citric acid in industrial standards [6]. Aspergillus nidulans constitutes a representative of this fungal genus that is capable of diverse and complex biosyntheses and differentiation processes. The most complicated developmental process includes the well-characterized sexual differentiation process where after mating with a compatible partner or “selfi ng,” closed fruitbodies, which are called cleistothecia, are formed which contain octades of ascospores [7,8]. During the last century, molecular methods were developed to easily investigate and manipulate these eukaryotic model organisms. Therefore, Aspergillus species are particularly suited for in-depth studies on regulatory networks and cross-connections between environmental stimuli, metabolism, and development and have steadily advanced our understanding of eukaryotic physiology. The aim of this chapter is to give an overview of the metabolic potential Aspergillus species have developed to acquire amino acids. By comprehensive genome analysis regarding uptake systems, the general control/cross-pathway control (gc/cpc) of amino acid biosynthesis and the COP9 signalosome (CSN) of A. nidulans, A. oryzae, A. niger, and A. fumigatus, we describe three concepts to obtain amino acid homeostasis in an Aspergillus cell in detail: (1) uptake of free amino acids, (2) energy consuming de novo biosynthesis, and (3) controlled recycling of used amino acids. A diagram of this concept is given in Figure 11.1, respective sources for all investigated sequences are given in Table 11.1 through 11.5. Fungi, plants, and prokaryotes are able to synthesize all amino acids, whereas mammals have to take up aromatic amino acids, which they are unable to produce [9]. For effi cient biosynthesis, a well-characterized gc system, cpc, evolved, which is responsible for the regulation of amino acid biosynthesis. A similar control mechanism is known from yeast, where it is called general control (gc). Both systems have a central, global activator of transcription in common: CpcA for Aspergillus and Gcn4p for S. cerevisiae. This transcriptional activator is conserved from yeast to man, where ATF4 plays a role similar to CpcA and Gcn4p [10]. However, even fungi prefer to take up amino acids from their diet, which is simply less energy consuming than amino acid de novo biosynthesis.
