酿酒酵母非发酵代谢调控
2007-06-17 14:48:04   来源：网络数据库   评论：0 点击：

mmermann 1980;Matsumoto et al. 1983; Neigeborn and Carlson 1987)led to high-level biosynthesis of invertase, maltase and GAL gene products, even in the presence of glucose, but was less pleiotropic compared with the phenotype of mig1, cyc8 and tup1 mutants discussed above. The identification of the first glycolytic enzyme (hexokinase PII, encoded by HXK2) as a regulatory factor led to the hypothesis of a molecular switch, triggering glucose repression as a result of substrate recognition or its conversion (Entian and Mecke 1982). Although Hxk2 is of central importance for the repression of at least some glucose-regulated genes in yeast and even plants (reviewed by Rolland et al. 2001), its precise function is not really understood. Hxk2 may exert a dual function as a sensory component in the cytoplasm and as a DNAbinding factor in the nucleus (Herrero et al. 1998). GLC7 (which is an essential gene in S. cerevisiae) and REG1 encode a protein phosphatase type 1 and its corresponding regulatory subunit, respectively (Tu and Carlson 1995). Reg1 interacts with the catalytic domain of Snf1 under glucose-limiting conditions (Ludin et al.1998), thereby targeting the Glc7 phosphatase to the kinase complex. Different (although overlapping) regions of Reg1 interact with Snf1 and Glc7 (Sanz et al.2000a). Reg1 and Snf1 are also contacted by Sip5 which may increase the interaction of both proteins (Sanz et al.2000b). These findings suggest that the Glc7-Reg1 phosphatase complex is responsible for the dephosphorylation of Snf1 substrate proteins. Reg1 itself may be a substrate of Snf1 under derepressing conditions and a substrate of Glc7 when glucose is available (Sanz et al.2000a). Upon phosphorylation, interaction of Reg1 with Snf1 is substantially weakened, indicating the release of Reg1-Glc7 from the Snf1 kinase complex. A pattern of phosphorylation (under derepressing conditions) and dephosphorylation (under repressing conditions) similar to that observed with Reg1 was also shown for the hexokinase PII (Randez-Gil et al. 1998). In the absence of Hxk2 and Reg1, the glucose-regulated interaction of Snf1 and Snf4 seen in the wild-type no longer occurs. Instead, hxk2 and reg1 mutants show a Snf1-Snf4 interaction at a high constitutive level (Sanz et al.2000a). Reg1-Glc7 is also required for the dephosphorylation of Thr-210 of Snf1, converting the kinase into an inactive state (McCartney and Schmidt 2001). In contrast, deactivation of Snf1 is absent in hxk2 and reg1 mutants. Thus, both mutants allow constitutive phosphorylation of Mig1 by Snf1, leading to functional deactivation of the repressor and its export from the nucleus. Consequently, Mig1-dependent repression is abolished, leading to high-level expression of its target genes. In contrast to previous results (Niederacher and Entian 1991), Reg1 may not be a nuclear protein (Dombek et al. 1999). Thus, phosphorylation of Mig1 by the Snf1 complex under derepressing conditions occurs in the nucleus while dephosphorylation by Reg1-Glc7 under repressing conditions is a cytoplasmic event (summarized in Fig. 4). Regulators Hxk2, Reg1and Glc7 clearly affect the glucose regulation of genes involved in the utilization of alternative sugars. However, genes of nonfermentative pathways remain glucose-repressed in hxk2 and reg1 null mutants (with the exception of Adr1-dependent expression of ADH2; see section below), arguing for a different mechanism of signal transduction.

Regulation of mitochondrial respiration
ATP generated in the course of glycolysis allows S. cerevisiae to proliferate, even in the absence of mitochondrial respiration. However, mitochondria as the organelles of oxidative phosphorylation are indispensable for the generation of energy under nonfermentative growth conditions. Biosynthesis of mitochondrial proteins is controlled by the availability of carbon source, oxygen and heme, affecting both the nuclear and the organelle genome (Grivell 1995). Gene regulation by oxygen and heme (reviewed by Kastaniotis and Zitomer 2000), which involves the transcriptional repressor Rox1 and the activator Hap1, respectively, is not considered here.

Repression of respiratory activities by glucose even in the presence of oxygen was observed quite early (Strittmatter 1957; Polakis et al. 1965). However, a considerable variation in carbon source regulation of mitochondrial proteins, even among well established laboratory strains, has been described (Brown and Trumpower 1995). Such a regulatory diversity agrees with results obtained after continuous aerobic growth of S. cerevisiae in glucose-limited chemostats. Under these conditions, alleviation of the glucose control of respiratory functions should provide an adaptive advantage. Indeed, genes of the TCA cycle and oxidative phosphorylation showed significantly altered patterns of expression. Thus, adaptive evolution led to an altered regulation of metabolism, such that more glucose was completely oxidized (Ferea et al. 1999).