Microbial methionine transporters and biotechnological applications

Abstract

Methionine (Met) is an essential amino acid with commercial value in animal feed, human nutrition, and as a chemical precursor. Microbial production of Met has seen intensive investigation towards a more sustainable alternative to the chemical synthesis that currently meets the global Met demand. Indeed, efficient Met biosynthesis has been achieved in genetically modified bacteria that harbor engineered enzymes and streamlined metabolic pathways. Very recently, the export of Met as the final step during its fermentative production has been studied and optimized, primarily through identification and expression of microbial Met efflux transporters. In this mini-review, we summarize the current knowledge on four families of Met export and import transporters that have been harnessed for the production of Met and other valuable biomolecules. These families are discussed with respect to their function, gene regulation, and biotechnological applications. We cover methods for identification and characterization of Met transporters as the basis for the further engineering of these proteins and for exploration of other solute carrier families. The available arsenal of Met transporters from different species and protein families provides blueprints not only for fermentative production but also synthetic biology systems, such as molecular sensors and cell-cell communication systems. KEY POINTS: • Sustainable production of methionine (Met) using microbes is actively explored. • Met transporters of four families increase production yield and specificity. • Further applications include other biosynthetic pathways and synthetic biology.

Keywords: Amino acids; Cell engineering; Fermentation; Membrane transport; Solute efflux; Synthetic biology.

Fig. 1

Met transporters harnessed in biomolecule production. a Topology and membrane orientation of Met transporters. Pp: periplasm. Cyt: cytosol. Out: Extracellular space. N: N-terminus. C: C-terminus. b Transport activities are to increase Met efflux or, in one case, increase Met influx. c Known substrates. Transporter cartoons are placed in circles and boxes that represent their substrates. For instance, YjeH is a carrier of Met, Leu, Ile, and Val but not Ser or His