Genome Analysis of The Salt-Resistant Paludifilum Halophilum DSM 102817T Reveals Genes Involved In Flux-Tuning of Ectoines And Unexplored Bioactive Secondary Metabolites

Abstract Paludifilum halophilum is the first member of the genus Paludifilum in the Thermoactinomycetaceae family. The thermohalophilic bacterium was isoated from the solar saltern of Sfax, in Tunisia and was shown to be able to produce ectoines in relatively high-yield and cope with salt stress conditions. In this study, the whole genome of P. halophilum was sequenced and analysed. Analysis revealed 3,789,765 base pairs with average GC % content of 51.5%. A total of 3,775 genes were predicted of which 3616 were protein-coding genes and 73 were RNA genes. The genes encoding key enzymes for ectoines synthesis were identified from the bacterial genome next to a gene cluster (ehuABCD) encoding a binding-protein-dependent ABC transport system responsible for ectoines mobility through the cell membrane. With the aid of KEGG analysis, we found that the central catabolic network of P. halophilum comprises the pathways of glycolysis, tricarboxylic acid (TCA) cycle, and pentose phosphate pathway (PPP). In addition, anaplerotic pathways replenishing oxaloacetate and glutamate synthesis from central metabolism, both needed for high ectoines biosynthetic fluxes were identified through several key enzymes. Furthermore, a total of 18 antiSMASH-predicted putative biosynthetic gene clusters (BGCs) for secondary metabolites with high novelty and diversity were identified in P. halophilum genome, including biosynthesis of Colabomycine-A, Fusaricidin-E, Zwittermycin A, Streptomycin, Mycosubtilin and Meilingmycin. Based on these data, P. halophilum emerged as a promising source for ectoines and antimicrobials with the potential to be scaled up for industrial production, which could benefit the pharmaceutical and cosmetic industries.