The rise of antimicrobial resistance (AMR) leads to difficult-totreat nosocomial infections and is thus a threat for health care systems globally. Particularly some multidrug-resistant (MDR) Gram-negative pathogens belonging to the bacterial order of Enterobacterales, such as E. coli, have been ranked as critical priority by the World Health Organization (WHO). In some cases, those strains develop resistance towards almost all antibiotics currently used in the clinic, leaving no remaining treatment options. Most of the antibacterial drugs recently approved by the FDA derive from known antibiotic classes such as the aminoglycoside Plazomicin, the tetracycline derivative Eravacycline, and the β-lactam/β-lactamase inhibitor combinations Meropenem/Vaborbactam, Ceftolozane/Tazobactam and Ceftazidime/Avibactam. However, development of resistance to these drugs is highly probable since resistance mechanisms against their congeners do already exist among pathogens. Consequently, it is of utmost urgency to discover and develop new antibiotics in order to successfully fight infectious diseases in the future. Recently, a number of structures with new modes of action (MoA) were described: for example the Gram-negative outer membrane biogenesis disrupting compound Darobactin, the chimeric peptidomimetic combination of Murepavadin and Polymyxin B1, and the small molecule MRL-494. Another example are the Griselimycins, which are highly active against Mycobacterium tuberculosis by inhibiting the new antimicrobial target DnaN, the DNA polymerase sliding clamp. Nevertheless, those antimicrobials are still under investigation and the discovery of antibiotic classes with new MoA against Gram-negative pathogens remains indispensable. The main source of new structures in the antibiotic drug discovery process are natural products from bacteria, historically in particular from actinomycetes. However, previous screening efforts and recent bioinformatic analyses of the genomes of myxobacteria (Gram-negative δ-proteobacteria with the largest known genomes in the bacterial domain), revealed an equal potential for the biosynthesis of natural products for this bacterial order. Myxobacterial genomes contain 6-10 % biosynthetic genes in 10-40 different biosynthetic gene clusters (BGCs) on average, making them the perfect candidates for future drug screening efforts. Microbial natural products are very often produced by multifunctional enzyme complexes via two major pathways: the polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs). The multi-modularity, functionality and plasticity of PKS and NRPS systems are described in detail elsewhere. Briefly summarized, both systems follow a similar assembly line logic, in which a cascade of condensation reactions links simple monomeric building blocks. In silico identification and analysis of secondary metabolite gene clusters encoding those mega enzymes in bacterial genomes improved genome mining approaches in the past, e.g., with software like antiSMASH. Moreover, the automated annotation of potential BGCs, the prediction of domain organization or substrate specificities in PKS and NRPS modules enable the assignment of known metabolites to previously unknown BGCs and predictions of the compound`s stereochemistry based on DNA sequence analysis. The stereochemistry of amino acids in non-ribosomally biosynthesized peptides can often be predicted by determination of the functional subtype of a condensation (C) domain. L CL domains catalyze peptide bond formation between two L-amino acids, whereas D CL domains connect a D-amino acid with an L-amino acid.