Chiral alcohols constitute important building blocks that can be produced enantioselectively by using nicotinamide adenine dinucleotide (phosphate) [NAD(P)H]‐dependent oxidoreductases. For NAD(P)H regeneration, electricity delivers the cheapest reduction equivalents. Enzymatic electrosynthesis suffers from cofactor and enzyme instability, whereas microbial electrosynthesis (MES) exploits whole cells. Here, we demonstrate MES by using resting Escherichia coli as biocatalytic chassis for a production platform towards fine chemicals through electric power. This chassis was exemplified for the synthesis of chiral alcohols by using a NADPH‐dependent alcohol dehydrogenase from Lactobacillus brevis for synthesis of (R)‐1‐phenylethanol from acetophenone. The E. coli strain and growth conditions affected the performance. Maximum yields of (39.4±5.7) % at a coulombic efficiency of (50.5±6.0) % with enantiomeric excess >99 % was demonstrated at a rate of (83.5±13.9) μm h−1, confirming the potential of MES for synthesis of high‐value compounds.
A variety of enzymes can be easily incorporated and overexpressed within Escherichia coli cells by plasmids, making it an ideal chassis for bioelectrosynthesis. It has recently been demonstrated that microbial electrosynthesis (MES) of chiral alcohols is possible by using genetically modified E. coli with plasmid‐incorporated and overexpressed enzymes and methyl viologen as mediator for electron transfer. This model system, using NADPH‐dependent alcohol dehydrogenase from Lactobacillus brevis to convert acetophenone into (R)‐1‐phenylethanol, is assessed by using a design of experiment (DoE) approach. Process optimization is achieved with a 2.4‐fold increased yield of 94±7 %, a 3.9‐fold increased reaction rate of 324±67 μm h−1, and a coulombic efficiency of up to 68±7 %, while maintaining an excellent enantioselectivity of >99 %. Subsequent scale‐up to 1 L by using electrobioreactors under batch and fed‐batch conditions increases the titer of (R)‐1‐phenylethanol to 12.8±2.0 mm and paves the way to further develop E. coli into a universal chassis for MES in a standard biotechnological process environment.
Invited for this month′s cover are the groups of Falk Harnisch at the Helmholtz‐Centre for Environmental Research – UFZ in Leipzig and of Antje C. Spieß at the TU Braunschweig. The image illustrates the essence of the outcome of their collaborative work: to have demonstrated that the workhorse of white biotechnology E. coli can serve as a chassis for the microbial electrochemical production of chiral compounds. The Communication itself is available at 10.1002/cssc.201900413.
The Front Cover shows Escherichia coli (E. coli) as a production chassis for microbial electrochemical synthesis. This was exemplified for the conversion of acetophenone to (R)‐1‐phenylethanol with a stereoselectivity of >99 %ee by a heterologously expressed alcohol dehydrogenase of Lactobacillus brevis. The wiring of the NAD(P)+/NAD(P)H,H+ ‐ pool of E. coli to the electrode was achieved using methyl viologen, which is colorless if oxidized and deep violet in its reduced state, as mediator combined with molecular engineering using “wire” proteins from the periplasm of Shewanella oneidensis, being a model for electroactive microorganisms. This proof‐of‐concept already demonstrates a coulombic efficiency of up to 50% and a yield of approximately 40%. Thus, the work clearly lays the foundation for further microbial electrochemical synthesis of valuable pharmaceuticals and chemical building blocks. More information can be found in the Communication by J. C. Mayr et al. on page 1631 in Issue 8, 2019 (DOI: 10.1002/cssc.201900413).
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