Cascade Biotransformation to Access 3‐Methylpiperidine in Whole Cells

• Published in: ChemCatChem Vol. 11; no. 23; pp. 5738 - 5742
• Main Authors: Borlinghaus, Niels, Weinmann, Leonie, Krimpzer, Florian, Scheller, Philipp N., Al‐Shameri, Ammar, Lauterbach, Lars, Coquel, Anne‐Sophie, Lattemann, Claus, Hauer, Bernhard, Nestl, Bettina M.
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 05.12.2019
• Subjects: amine oxidase; Bioconversion; Bioreactors; Biotransformation; Cultivation; Diamines; E coli; imine reductase; methylpiperidine; Optimization; Process parameters; Reductases; Rhodococcus; Substrates; upscaling; whole cell enzyme cascade
• ISSN: 1867-3880; 1867-3899
• DOI: 10.1002/cctc.201900702

Synthesis of 3‐methylpiperidine from 1,5‐diamino‐2‐methylpentane in preparative scale is reported by using recombinant Escherichia coli cells expressing a variant of the diamine oxidase from Rhodococcus erythroprolis and an imine reductase from Streptosporangium roseum. Optimization of process parameters for cultivation and bioconversion led to substantial improvements in the initial laboratory procedure. The transformation of the methyl‐substituted diamine substrate to the N‐heterocyclic product was successfully scaled‐up from shake‐flask to a 20 L bioreactor with increased substrate concentrations. Remarkably, we obtained 67 % of 3‐methylpiperidine product from 140 g substrate within 52 h. Scaling Up! The coupling of engineered putrescine oxidase and imine reductase realizes the preparation of piperidine heterocycles. Particularly, the production of 3‐methylpiperidine at 20 L scale was demonstrated using an E. coli whole‐cell system.