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  • Title: Control Mechanism for Carbon-Chain Length in Polyunsaturated Fatty-Acid Synthases.
    Author: Hayashi S, Naka M, Ikeuchi K, Ohtsuka M, Kobayashi K, Satoh Y, Ogasawara Y, Maruyama C, Hamano Y, Ujihara T, Dairi T.
    Journal: Angew Chem Int Ed Engl; 2019 May 13; 58(20):6605-6610. PubMed ID: 30848057.
    Abstract:
    Polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are essential fatty acids. PUFA synthases are composed of three to four subunits and each create a specific PUFA without undesirable byproducts. However, detailed biosynthetic mechanisms for controlling final product profiles have been obscure. Here, the bacterial DHA and EPA synthases were carefully dissected by in vivo and in vitro experiments. In vitro analysis with two KS domains (KSA and KSC ) and acyl-acyl carrier protein (ACP) substrates showed that KSA accepted short- to medium-chain substrates while KSC accepted medium- to long-chain substrates. Unexpectedly, condensation from C18 to C20 , the last elongation step in EPA biosynthesis, was catalyzed by KSA domains in both EPA and DHA synthases. Conversely, condensation from C20 to C22 , the last elongation step for DHA biosynthesis, was catalyzed by the KSC domain in DHA synthase. KSC domains therefore determine the chain lengths.
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