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A highly active alkaline phosphatase (ALP) of the protein structural family PhoA, from a mussel gut-associated strain of the marine bacterium <i>Cobetia amphilecti</i> KMM 296 (CmAP), was found to effectively dephosphorylate lipopolysaccharides (LPS). Therefore, the aim of this work was to perform a comprehensive bioinformatics analysis of the structure, and to suggest the physiological role of this enzyme in marine bacteria of the genus <i>Cobetia</i>. A scrutiny of the CmAP-like sequences in 36 available <i>Cobetia</i> genomes revealed nine homologues intrinsic to the subspecies <i>C. amphilecti</i>, whereas PhoA of a distant relative <i>Cobetia crustatorum</i> JO1^T carried an inactive mutation. However, phylogenetic analysis of all available <i>Cobetia</i> ALP sequences showed that each strain of the genus <i>Cobetia</i> possesses several ALP variants, mostly the genes encoding for PhoD and PhoX families. The <i>C. amphilecti</i> strains have a complete set of four ALP families’ genes, namely: PhoA, PafA, PhoX, and two PhoD structures. The <i>Cobetia marina</i> species is distinguished by the presence of only three PhoX and PhoD genes. The <i>Cobetia</i> PhoA proteins are clustered together with the human and squid LPS-detoxifying enzymes. In addition, the predicted PhoA biosynthesis gene cluster suggests its involvement in the control of cellular redox balance, homeostasis, and cell cycle. Apparently, the variety of ALPs in <i>Cobetia</i> spp. indicates significant adaptability to phosphorus-replete and depleted environments and a notable organophosphate destructor in eco-niches from which they once emerged, including <i>Zostera</i> spp. The ALP clusterization and degree of similarity of the genus-specific biosynthetic genes encoding for ectoine and polyketide cluster T1PKS, responsible for sulfated extracellular polysaccharide synthesis, coincide with a new whole genome-based taxonomic classification of the genus <i>Cobetia</i>. The <i>Cobetia</i> strains and their ALPs are suggested to be adaptable for use in agriculture, biotechnology and biomedicine.