Semi-pilot scale-up of a continuous packed-bed bioreactor system developed for the lipase-catalyzed production of pseudo-ceramides

Abstract : Ceramides are sphingolipid compounds that are very attractive as active components in both the pharmaceutical and the cosmetic industries. In this study, the synthesis of 1-O,3-N-diacyl 3-amino-1,2-propanediol-type pseudo-ceramides was developed at the semi-pilot scale, starting from a two-step continuous enzymatic process with immobilized Candida antarctica lipase B (Novozym ® 435) in a packed-bed bioreactor, previously optimized at the laboratory scale. This process involved the selective N-acylation of 3-amino-1,2-propanediol (step 1), followed by the selective O-acylation of the N-acyl 3-amino-1,2-propanediol synthesized in the first step, with various fatty acids as acyl donors, to produce N,O-diacyl 3-amino-1,2-propanediol-type pseudo-ceramides (step 2). Under partially optimized operating conditions, high synthesis yields and production rates were obtained, within the ranges 76–92% and 3.7–4.6 g h À1 (step 1), or 23–36% and 1–1.4 g h À1 (step 2), respectively, depending on the fatty acids used as acyl donors. The overall synthesis yields varied from 20 to 33%: the best yield was obtained using palmitic acid and lauric acid as first and second acyl donors, respectively. Together with the high production rates also obtained with these acyl donors, this confirms that this two-step process has great potential for the production of differently functionalized 1-O,3-N-diacyl 3-amino-1,2-propanediol-type pseudo-ceramides on an industrial scale. Keywords: pseudo-ceramide / continuous bioprocess / packed-bed bioreactor / lipase / semi-pilot scale
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Florian Le Joubioux, Nicolas Bridiau, Marianne Graber, Thierry Maugard. Semi-pilot scale-up of a continuous packed-bed bioreactor system developed for the lipase-catalyzed production of pseudo-ceramides. OCL Oilseeds and fats crops and lipids, EDP, 2017, 24 (4), ⟨10.1051/ocl/2017019⟩. ⟨hal-01630116⟩

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