Non-ribosomal peptide synthetases (NRPSs) are a primary modality for fungal peptidic natural product assembly and are responsible for some of the best known, most useful, and most destructive fungal metabolites. Through genome sequencing and computer-assisted recognition of modular motifs of catalytic domains, one can now confidently identify most NRPS biosynthetic genes of a fungal strain. The...

Nurse Rostering Problems (NRPs) consist of generating rosters where required shifts are assigned to nurses over a scheduling period satisfying a number of constraints. In [25], we have shown how soft global constraints can be used to model NRPs in a concise and elegant way. In this paper we go one step further by proposing new neighborhood heuristics for VNS/LDS+CP. Experiments show that, despi...

The filamentous fungus Penicillium chrysogenum harbors an astonishing variety of nonribosomal peptide synthetase genes, which encode proteins known to produce complex bioactive metabolites from simple building blocks. Here we report a novel non-canonical tetra-modular nonribosomal peptide synthetase (NRPS) with microheterogenicity of all involved adenylation domains towards their respective sub...

Virginiamycin M (VM) of Streptomyces virginiae is a hybrid polyketide-peptide antibiotic with peptide antibiotic virginiamycin S (VS) as its synergistic counterpart. VM and VS belong to the Streptogramin family, which is characterized by strong synergistic antibacterial activity, and their water-soluble derivatives are a new therapeutic option for combating vancomycin-resistant Gram-positive ba...

Some of the most therapeutically interesting natural products are mixed polyketide/nonribosomal peptide molecules, including bleomycin and epothilones (anticancer agents) and FK506 and rapamycin (immunosuppressive drugs).1-3 These enzymatically assembled molecules are encoded by multimodular protein arrays that, through their chain-ordering, determine the structure of the natural product elonga...

Worldwide, older people’s support used to be the adult children’s responsibility. In China, two generations after introducing the one-child policy in the late 70-ies, this becomes an increasingly demanding obligation. The Chinese government took the responsibility to mitigating oldage poverty risks and realized unprecedented progress in pension coverage. At the same time, the household savings ...

Considering that 70% of our planet's surface is covered by oceans, it is likely that undiscovered biodiversity is still enormous. A large portion of marine biodiversity consists of microbiomes. They are very attractive targets of bioprospecting because they are able to produce a vast repertoire of secondary metabolites in order to adapt in diverse environments. In many cases secondary metabolit...

Recently, the solved crystal structure of a phenylalanine-activating adenylation (A) domain enlightened the structural basis for the specific recognition of the cognate substrate amino acid in nonribosomal peptide synthetases (NRPSs). By adding sequence comparisons and homology modeling, we successfully used this information to decipher the selectivity-conferring code of NRPSs. Each codon combi...

BACKGROUND Dermatophyte fungi of the family Arthrodermataceae (Eurotiomycetes) colonize keratinized tissue, such as skin, frequently causing superficial mycoses in humans and other mammals, reptiles, and birds. Competition with native microflora likely underlies the propensity of these dermatophytes to produce a diversity of antibiotics and compounds for scavenging iron, which is extremely scar...