Details

Autor(en) / Beteiligte

• Le Joubioux, Florian
• Bridiau, Nicolas
• Sanekli, Mehdi
• Graber, Marianne
• Maugard, Thierry

Titel

Continuous lipase-catalyzed production of pseudo-ceramides in a packed-bed bioreactor

Ist Teil von

• Journal of molecular catalysis. B, Enzymatic, 2014-11, Vol.109, p.143-153

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

2014

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •We report the continuous Novozym® 435-catalyzed synthesis of pseudo-ceramides.•A packed-bed bioreactor is developed and optimized.•Chemoselective synthesis of pseudo-ceramides gives good yield and productivity.•Novozym® 435 can operate for more than 3 weeks without a drop in yield.•A 4-fold scale-up shows encouraging results for a future pilot scale development. Ceramides are spingolipid compounds that are very attractive as active components in both the pharmaceutical and the cosmetic industries. In this study, the synthesis of ceramide analogs, the so-called pseudo-ceramides, was carried out using for the first time a two-step continuous enzymatic process with immobilized Candida antarctica lipase B (Novozym® 435) in a packed-bed bioreactor. The first step involved the selective N-acylation of 3-amino-1,2-propanediol using stearic acid as the first acyl donor (i). This was followed by the selective O-acylation of the N-stearyl 3-amino-1,2-propanediol synthesized in the first step, with myristic acid as the second acyl donor, to produce a N,O-diacyl 3-amino-1,2-propanediol-type pseudo-ceramide, namely 1-O-myristyl,3-N-stearyl 3-amino-1,2-propanediol (ii). The process was first optimized by evaluating the influences of three factors: feed flow rate, quantity of biocatalyst and substrate concentration. Under optimal conditions an amide synthesis yield of 92% and a satisfying production rate of almost 3.15mmolh−1gbiocatalyst−1 (1128mgh−1gbiocatalyst−1) were obtained. The second step, N-acyl 3-amino-1,2-propanediol O-acylation, was similarly optimized and in addition the effect of the substrate molar ratio was studied. Thus, an optimal pseudo-ceramide synthesis yield of 54% and a production rate of 0.46mmolh−1gbiocatalyst−1 (261mgh−1gbiocatalyst−1) were reached at a 1:3 ratio of amide to fatty acid. In addition, it was demonstrated that this two-step process has great potential for the production of N,O-diacyl 3-amino-1,2-propanediol-type pseudo-ceramides on an industrial scale. It was shown in particular that Novozym® 435 could be used for more than 3 weeks without a drop in the yield during the first step of 3-amino-1,2-propanediol N-acylation, proving that this biocatalyst is very stable under these operational conditions. This factor would greatly reduce the need for biocatalyst replacement and significantly lower the associated cost.