TY - JOUR

T1 - A Fed-Batch Synthetic Strategy for a Three-Step Enzymatic Synthesis of Poly-ϵ-caprolactone

AU - Scherkus, Christian

AU - Schmidt, Sandy

AU - Bornscheuer, Uwe T.

AU - Gröger, Harald

AU - Kara, Selin

AU - Liese, Andreas

PY - 2016/11/23

Y1 - 2016/11/23

N2 - A three-step enzymatic reaction sequence for the synthesis of poly-ϵ-caprolactone (PCL) was designed running in a fed-batch operation. The first part of the cascade consisted of two oxidation steps starting with alcohol dehydrogenase catalyzed oxidation from cyclohexanol to cyclohexanone and further oxidation to ϵ-caprolactone (ECL) by means of a Baeyer–Villiger monooxygenase. As a third step, lipase-catalyzed hydrolysis of the lactone to 6-hydroxyhexanoic acid (6-HHA) was designed. With this biocatalytic multistep process reported herein, severe substrate surplus and product inhibition could be circumvented by the fed-batch operation by adding the cyclohexanol substrate and by in situ product removal of ECL by hydrolysis, respectively. Up to 283 mm product concentration of 6-HHA was reached in the fed-batch operated process without loss in productivity within 20 h. After extraction and subsequent polymerization catalyzed by Candida antarctica lipase B, analysis of the unfractionated polymer revealed a bimodal distribution of the polymer population, which reached a mass average molar mass (Mw) value of approximately 63 000 g mol−1 and a dispersity (Mw/Mn) of 1.1 for the higher molecular weight population, which thus revealed an alternative route to the conventional synthesis of PCL.

AB - A three-step enzymatic reaction sequence for the synthesis of poly-ϵ-caprolactone (PCL) was designed running in a fed-batch operation. The first part of the cascade consisted of two oxidation steps starting with alcohol dehydrogenase catalyzed oxidation from cyclohexanol to cyclohexanone and further oxidation to ϵ-caprolactone (ECL) by means of a Baeyer–Villiger monooxygenase. As a third step, lipase-catalyzed hydrolysis of the lactone to 6-hydroxyhexanoic acid (6-HHA) was designed. With this biocatalytic multistep process reported herein, severe substrate surplus and product inhibition could be circumvented by the fed-batch operation by adding the cyclohexanol substrate and by in situ product removal of ECL by hydrolysis, respectively. Up to 283 mm product concentration of 6-HHA was reached in the fed-batch operated process without loss in productivity within 20 h. After extraction and subsequent polymerization catalyzed by Candida antarctica lipase B, analysis of the unfractionated polymer revealed a bimodal distribution of the polymer population, which reached a mass average molar mass (Mw) value of approximately 63 000 g mol−1 and a dispersity (Mw/Mn) of 1.1 for the higher molecular weight population, which thus revealed an alternative route to the conventional synthesis of PCL.

KW - enzymatic cascade

KW - enzymes

KW - oxidoreductases

KW - polymerization

KW - ϵ-caprolactone

UR - http://www.scopus.com/inward/record.url?scp=85027956629&partnerID=8YFLogxK

U2 - 10.1002/cctc.201600806

DO - 10.1002/cctc.201600806

M3 - Article

AN - SCOPUS:85027956629

VL - 8

SP - 3446

EP - 3452

JO - CHEMCATCHEM

JF - CHEMCATCHEM

SN - 1867-3880

IS - 22

ER -