Metabolic engineering of yeast to efficiently synthesize heme and hemoproteins: recent advance and prospects

Abstract

Owing to the potential for commercialization, the recombinant production of hemoproteins has been heavily investigated. Yeast is a superior host for the synthesis of eukaryotic hemoproteins with optimal pathway to facilitate heme delivery and utilization, as well as suitable environment for the post-translational folding and modification. The efficient binding of heme is the critical determinant for the various functions of hemeproteins. Thus, many metabolic engineering strategies have been employed to modify heme synthetic pathways and balance the intracellular metabolic burden. This paper provides a comprehensive review on the improvement of heme supply, the enhancement of hemoprotein expression, and the current efforts to harmonize the synthesis of heme and the expression of protein components in yeast. These insights offer a solid foundation for the development of yeast chassis for the efficient production of high-active hemoproteins in the future.

Keywords: balance; heme; hemoprotein; metabolic engineering; yeast.

Figure 1.

Heme metabolic pathways in yeast and targets that have been applied to enhance heme or hemoprotein synthesis. GLC: glucose; G6P: glucose 6-phosphate; 3PG: 3-phosphoglyceric acid; PYR: pyruvic acid; Ser: serine; Gly: glycine; CIT: citrate; ISO-CIT: isocitrate; α-KG: α-ketoglutarate; SUC-CoA: succinyl-CoA; SUC: succinate; FUM: fumarate; MAL: malate; L-Glu: L-glutamic acid; L-Glu-tRNA: L-glutamyl-tRNA; GSA: glutamate-1-semialdehyde; 5-ALA: 5-aminolevulinic acid; PBG: porphobilinogen; HMB: hydroxymethylbilane; UPG III: uroporphyrinogen III; CPG III: coproporphyrinogen III; PPG IX: protoporphyrinogen IX; PPIX: protoporphyrin IX; BV: biliverdin. This figure was created with the assistance of FIGDRAW.