C-di-GMP and Its Role in Regulation of Natural Products Production

Natural products play a crucial role in the development of drugs. Over the last forty years one third of all approved drugs are natural products or derivatives from them. Additionally, another third uses at least a pharmacophore of a natural product. The therapeutic areas do not only cover the widely known fields of antibiotics and cytostatics, but also anticoagulants, anti-hypertensive or anti-diabetic drugs and many more [1]. Nevertheless, antibiotics are one of the most prominent fields for natural products. Increasing antibiotic resistance in the upcoming years is leading to an urgent need for the development of new antibiotics [2]. The World Health Organization stated the antibiotic resistance crisis to be a “global public health concern”. Also, the Center for Disease Control and Prevention and the European Medicines Agency are substantially concerned about the course in the last decades [2-4]. Streptomyces, a genus of the family Streptomycetaceae and the class Actinobacteria, are the largest source of natural products among microorganisms. A large proportion of all antibiotics originally derive from them [5]. However, in the last years only a handful of new drugs in the antibiotic field were approved. So, there is an urgent need to search for new natural compounds beyond of the existing ones [6]. A high rate of rediscovered compounds is one problem of common techniques for screening for new Abstract