Work

Inhibition Control by Continuous Extractive Fermentation Enhances De Novo 2‐Phenylethanol Production by Yeast

Year: 2024

Type: article

Abstract: ABSTRACT Current microbial cell factory methods for producing chemicals from renewable resources primarily rely on (fed‐)batch production systems, leading to the accumulation of the desired product. Industrially relevant chemicals like 2‐phenylethanol (2PE), a flavor and fragrance compound, can exhibit toxicity at low concentrations, inhibit the host activity, and negatively impact titer, rate, and yield. Batch liquid‐liquid (L‐L) In Situ Product Removal (ISPR) was employed to mitigate inhibition effects, but was not found sufficient for industrial‐scale application. Here, we demonstrated that continuous selective L‐L ISPR provides the solution for maintaining the productivity of de novo produced 2PE at an industrial pilot scale. A unique bioreactor concept called “Fermentation Accelerated by Separation Technology” (FAST) utilizes hydrostatic pressure differences to separate aqueous‐ and extractant streams within one unit operation, where both production and product extraction take place ‐ allowing for the control of the concentration of the inhibiting compound. Controlled aqueous 2PE levels (0.43 ± 0.02 g kg −1 ) and extended production times (>100 h) were obtained and co‐inhibiting by‐product formation was reduced, resulting in a twofold increase of the final product output of batch L‐L ISPR approaches. This study establishes that continuous selective L‐L ISPR, enabled by FAST, can be applied for more economically viable production of inhibiting products.

Source: Biotechnology and Bioengineering

DOI: 10.1002/bit.28872