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Introduction
Interaction of global regulators: a novel aspect of systems biology in streptomycetes
Extracellular environmental signals (e.g. pH stress or heat shock) and nutrient limitation signals are transduced through global regulators that in turn activate pathway‐specific regulators (Rigali et al., 2008; Martín and Liras, 2010). During the past decade important advances have been made in our understanding of the mechanisms of control of primary and secondary metabolism in Streptomyces species by the limitation of different nutrients including (i) phosphate (Sola‐Landa et al., 2003; 2008; Martín, 2004; Rodríguez‐García et al., 2007; 2009), (ii) easily utilized nitrogen sources (e.g. ammonium) (Wray et al., 1991; Wray and Fisher, 1993; Fink et al., 2002; Hesketh et al., 2002; Tiffert et al., 2008), and (iii) glucose or other easily utilized carbon sources (the so‐called carbon catabolite regulation) (Borodina et al., 2008). There is also an interesting mechanism of regulation of the Streptomyces coelicolor metabolism by N‐acetyl‐glucosamine (Rigali et al., 2008).
Each of these mechanisms is mediated by a global regulator that may be a member of a two‐component system or an orphan global regulator. Phosphate control is mediated by the PhoR–PhoP system (Sola‐Landa et al., 2003; 2005); nitrogen metabolism is controlled by the orphan response regulator, GlnR (and perhaps GlnRII; see below) (Wray et al., 1991; Wray and Fisher, 1993), and the chitin degradation and N‐acetyl‐glucosamine metabolism is mediated by a member of the GntR family (Rigali et al., 2008). We will not describe in detail these regulatory mechanisms in this minireview since they have been reviewed previously (Martín, 2004; Rigali et al., 2008; Tiffert et al., 2008).
Our interest concentrates on the interactions between nutritional global regulators, a subject that has emerged in the last few years as a promising field to understand the coordination of metabolism and the response to different nutritional factors in Streptomyces (Martín and Liras, 2010). The interaction between global regulators described below allows the cells to maintain an equilibrium of nutritional pathways (nutrient homeostasis), an aspect of great interest in natural conditions in the soil where feast and famine episodes are frequent....