SimReg1 is a master switch for biosynthesis and export of simocyclinone D8 and its precursors

The actinomycetes, including in particular members of the genus Streptomyces, are the industrial source for a large number of bioactive compounds employed as antibiotics and other drugs Horinouchi 2007; Bibb and Hesketh 2009. Actinomycetes produce these molecules as part of their ''secondary'' or nonessential metabolism van Wezel et al. 2009. Many Streptomyces species are capable of producing more than one secondary metabolite Ohnishi et al. 2008; van Wezel et al. 2009. The timing of the production of secondary metabolites and the amount of the accumulated compounds correlates with the environmental conditions and morphological differentiation van Wezel et al. 2009; Bibb et al. 2009; van Wezel et al. 2011. Furthermore, it has also been associated with the accumulation of small signaling molecules, such as ppGpp, microbial hormones, and late intermediates or end-products of the secondary metabolite biosynthetic pathways Ruiz et al. 2008; O'Rourke et al. 2009; Hsiao et al. 2009; Wang et al. 2009. The influence of all aforementioned factors in most cases is reflected to the activity of the pathway-specific regulatory genes, which are believed to be final checkpoints in the onset of antibiotic production Arias et al. 1999; Nuria et al. 2007; van Wezel et al. 2009; Pulsawat et al. 2007; Wang et al. 2009. Because most antibiotics are potentially lethal to the producing organism, the onset of antibiotic production should be under tight control and mechanisms of self-resistance of producing bacteria must exist. All this requires a precise regulatory network coordinating both, biosynthesis and resistance genes expression Le et al. 2009. That is why very often resistance genes are linked to antibiotic biosynthesis genes Tahlan et al. 2007; Ostash et al. 2008. As our understanding of secondary metabolism advances, it is becoming clear that the relationship between antibiotic production and resistance is more complicated than expected. For example, in S. coelicolor, along with