Microbial alcohol dehydrogenase screening for enantiopure lactone synthesis: Down-stream process from microtiter plate to bench bioreactor

作者：Boratynski F^*; Pannek J; Walczak P; Janik Polanowicz A; Huszcza E; Szczepanska E; Martinez Rojas E; Olejniczak T

来源：Process Biochemistry, 2014, 49(10): 1637-1646.

DOI：10.1016/j.procbio.2014.06.019

• Biooxidation
• Enantioselectivity
• Meso diol
• Lactone
• Microtiter plate
• Scaling-up

One-pot conversion with whole cells of bacteria was performed for biooxidation of meso monocyclic (3a-b) and bicyclic diols (3c-e) into corresponding chiral lactones of bicyclo[4.3.0]nonane structure (2a-b) as well as exo- and endo-bridged lactones with the structure of [2.2.1] (3c-d) and [2.2.2] (3e). Micrococcus sp. DSM 30771 was selected as biocatalyst with significant alcohol dehydrogenase activity. Among tested strains, microbial oxidation of meso diols 3a-e catalyzed by Micrococcus sp. afforded enantiomerically pure ((+)-(2S,3R)-2c (ee = 99%), (+)-(2S,3R)-2e (ee = 99%)) or enriched ((+)-(1S,5R)-2a (ee = 90%), (-)-(1S,5R)-2b (ee = 86%), (+)-(2S,3R)-2d (ee = 80%)) lactone moieties. Comparative study with respect to microbial cultivation as well as biooxidation was undertaken to verify agreement of secondary metabolite biosynthesis in different scales: from MTP (4 mL), across shake flask (100 mL) till bioreactor (4 L). The results from biotransformations showed quite similar dependence in oxidation of all substrates 3a-e in MTP and flasks as well, thereby confirmed the validity and reasonable approach of using MTP for preliminary studies.

• 出版日期2014-10