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Background  Some marine bacteria, such as  Moritella marina , produce the nutraceutical docosahexaenoic acid (DHA) thanks to a specific enzymatic complex called Pfa synthase.  Escherichia coli  heterologously expressing the  pfa  gene cluster from  M. marina  also produces DHA. The aim of this study was to find genetic or metabolic conditions to increase DHA production in  E. coli .    Results  First, we analysed the effect of the antibiotic cerulenin, showing that DHA production increased twofold. Then, we tested a series of single gene knockout mutations affecting fatty acid biosynthesis, in order to optimize the synthesis of DHA. The most effective mutant,  fabH , showed a threefold increase compared to wild type strain. The combination of cerulenin inhibition and  fabH  deletion rendered a 6.5-fold improvement compared to control strain. Both strategies seem to have the same mechanism of action, in which fatty acid synthesis via the canonical pathway (fab pathway) is affected in its first catalytic step, which allows the substrates to be used by the heterologous pathway to synthesize DHA.    Conclusions  DHA-producing  E. coli  strain that carries a  fabH  gene deletion boosts DHA production by tuning down the competing canonical biosynthesis pathway. Our approach can be used for optimization of DHA production in different organisms.    Electronic supplementary material  The online version of this article (10.1186/s12934-018-0928-5) contains supplementary material, which is available to authorized users.

fabH deletion increases DHA production in Escherichia coli expressing Pfa genes