Biosynthesis and Molecular Genetics of Polyketides in Marine Dinoflagellates

Marine dinoflagellates are the single most important group of algae that produce toxins, which have a global impact on human activities. The toxins are chemically diverse, and include macrolides, cyclic polyethers, spirolides and purine alkaloids. Whereas there is a multitude of studies describing the pharmacology of these toxins, there is limited or no knowledge regarding the biochemistry and molecular genetics involved in their biosynthesis. Recently, however, exciting advances have been made. Expressed sequence tag sequencing studies have revealed important insights into the transcriptomes of dinoflagellates, whereas other studies have implicated polyketide synthase genes in the biosynthesis of cyclic polyether toxins, and the molecular genetic basis for the biosynthesis of paralytic shellfish toxins has been elucidated in cyanobacteria. This review summarises the recent progress that has been made regarding the unusual genomes of dinoflagellates, the biosynthesis and molecular genetics of dinoflagellate toxins. In addition, the evolution of these metabolic pathways will be discussed, and an outlook for future research and possible applications is provided

Harnessing the potential of communication-mediating domains for the biocombinatorial synthesis of nonribosomal peptides

The interaction between enzymes of a nonribosomal peptide synthetase (NRPS) complex relies on the interplay of compatible sets of donor and acceptor communication-mediating (COM) domains. Hence, these domains are essential for the formation of a defined biosynthetic template, thereby directing the synthesis of a specific peptide product. Without the selectivity provided by different sets of COM domains, NRPSs should form random biosynthetic templates, which would ultimately lead to combinatorial peptide synthesis. This study aimed to exploit this inherent combinatorial potential of COM domains. Based on sequence alignments between COM domains, the crosstalk between different biosynthetic systems was predicted and experimentally proven. Furthermore, key residues important for maintaining (or preventing) NRPS interaction were identified. Point mutation of one of these key residues within the acceptor COM domain of TycC1 was sufficient to shift its selectivity from the cognate donor COM of TycB3 toward the noncognate donor COM domain of TycB1. Finally, an artificial NRPS complex was constructed, constituted of enzymes derived from three different biosynthetic systems. By virtue of domain fusions, the interactions between all enzymes were established by the same set of COM domains. Because of the abrogated selectivity, this universal communication system was able to simultaneously form two biosynthetic complexes that catalyzed the combinatorial synthesis of different peptide products

Neurodermatitis and sleep in early childhood - a review

Schlarb A, Brinkmann J, Doekel M, et al. Neurodermitis und Schlaf in der frühen Kindheit – ein Überblick. ALLERGOLOGIE. 2017;40(1):3-15.Neurodermatitis (better called atopic dermatitis or atopic eczema, AE) is a chronic inflammatory skin disorder, which often appears already in early childhood and may be associated with a reduced quality of life for affected children. Research in adult patients has shown that AE often is associated with sleep problems. There is, however, little published information regarding this point in childhood. The main target of this paper is to provide an overview of the current evidence for the relation between sleep and AE in early childhood. A systematic literature research was conducted to identify relevant studies. The seven studies detected for this age group show that similar to adults, children with AE have increased sleep problems. They experience reduced sleep efficiency and sleep duration with an increased sleep fragmentation and prolonged sleep onset latency. Moreover, the severity of the disease directly influences the sleep quality. In general, there are few studies, which address the described relations in childhood. Therefore, more systematic research is required in this area. It is important to diagnose and treat chronic skin diseases such as AE early in childhood also to prevent sleep problems and related adverse effects on children's psychological well-being and on future development of children