Bioconversion From Docosahexaenoic Acid to Eicosapentaenoic Acid in the Marine Bacterium Shewanella livingstonensis Ac10

Abstract

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which belong to the same class of long chain ω-3 polyunsaturated fatty acids (PUFAs), are present in marine γ-proteobacteria. In contrast to their de novo biosynthesis that has been intensively studied, their metabolic fates remain largely unknown. Detailed information regarding bacterial ω-3 PUFA metabolism would be beneficial for understanding the physiological roles of EPA/DHA as well as the industrial production of EPA, DHA, and other PUFAs. Our previous studies revealed that the EPA-producing marine bacterium Shewanella livingstonensis Ac10 produces EPA from exogenous DHA independently of de novo EPA biosynthesis, indicating the presence of an unidentified metabolic pathway that converts DHA into EPA. In this study, we attempted to reveal the molecular basis for the bioconversion through both in vivo and in vitro analyses. Mutagenesis experiments showed that the gene disruption of fadH, which encodes an auxiliary β-oxidation enzyme 2,4-dienoyl-CoA reductase, impaired EPA production under DHA-supplemented conditions, and the estimated conversion rate decreased by 86% compared to that of the parent strain. We also found that the recombinant FadH had reductase activity toward the 2,4-dienoyl-CoA derivative of DHA, whereas the intermediate did not undergo β-oxidation in the absence of the FadH protein. These results indicate that a typical β-oxidation pathway is responsible for the conversion. Furthermore, we assessed whether DHA can act as a substitute for EPA by using an EPA-less and conversion-deficient mutant. The cold-sensitive phenotype of the mutant, which is caused by the lack of EPA, was suppressed by supplementation with EPA, whereas the DHA-supplementation suppressed it to a lesser extent. Therefore, DHA can partly substitute for, but is not biologically equivalent to, EPA in S. livingstonensis Ac10.

Bacterial Diversity of Breast Milk in Healthy Spanish Women: Evolution from Birth to Five Years Postpartum

“…The levels of DHA were influenced by lactation time as well ( Table 6 ), and by dietary factors as nuts ( r = 0.284, p = 0.014) and cereal ( r = 0.318, p = 0.006) intake, but no association between Proteobacteria and these dietary factors was detected. Thus, Proteobacteria could be other factor that influences the levels of DHA in breast milk, as it has been demonstrated that some groups of Proteobacteria can synthetize omega-3 polyunsaturated fatty acids such as EPA (eicosapentaenoic) and DHA [ 70 , 71 ]. The genus Staphylococcus was positively correlated with C18:2 (n-6) 9,12 t ( r = 0.309, p = 0.035) and C18:2 (n-6) 10 t , 12 ( r = 0.301, p = 0.040) isomers [ 72 ].…”

Clostridium butyricum MIYAIRI 588 Modifies Bacterial Composition under Antibiotic-Induced Dysbiosis for the Activation of Interactions via Lipid Metabolism between the Gut Microbiome and the Host

“…and Colwellia spp. [40,41]. Hence, no study has revealed that gut bacteria can induce EPA production.…”

Multi-omic analyses identify mucosa bacteria and fecal metabolites associated with weight loss after fecal microbiota transplantation

“…Bacterial polyunsaturated fatty acid (PUFA) production, including EPA, was previously believed to be limited to marine bacteria, which has been reported in recent years in members of d-proteobacteria retrieved from soil samples. 44 However, to the best of our knowledge, no study has shown that original human bacteria can produce EPA directly. We found that B. bifidum, A. onderdonkii, and Bacteriodes vulgatus did not harbor enzyme genes that drove the EPA biosynthesis in prokaryotes by checking the fecal metagenomic and metatranscriptomic profiles, further suggesting that these bacteria may not be able to produce EPA.…”