Applications of the Whole-Cell System in the Efficient Biosynthesis of Heme

Abstract

Heme has a variety of functions, from electronic reactions to binding gases, which makes it useful in medical treatments, dietary supplements, and food processing. In recent years, whole-cell system-based heme biosynthesis methods have been continuously explored and optimized as an alternative to the low-yield, lasting, and adverse ecological environment of chemical synthesis methods. This method relies on two biosynthetic pathways of microbial precursor 5-aminolevulinic acid (C4, C5) and three known downstream biosynthetic pathways of heme. This paper reviews the genetic and metabolic engineering strategies for heme production in recent years by optimizing culture conditions and techniques from different microorganisms. Specifically, we summarized and analyzed the possibility of using biosensors to explore new strategies for the biosynthesis of heme from the perspective of synthetic biology, providing a new direction for future exploration.

High-level expression of leghemoglobin in Kluyveromyces marxianus by remodeling the heme metabolism pathway

“…The precursor for heme synthesis is 5-aminolevulinic acid (5-ALA). Depending on the species, the synthesis of 5-ALA can occur via the C5 pathway or the C4 pathway ( Su et al, 2023 ). Most bacteria use the C5 pathway, which involves the catalysis of glutamyl-tRNA synthetase (GltX), glutamyl-tRNA reductase (HemA), and glutamate-1-semialdehyde aminotransferase (HemL) to convert L-glutamate into 5-ALA ( Yang et al, 2016 ).…”

High-Level Bio-Based Production of Coproporphyrin in Escherichia coli

“…Given the commercial value and applicability of heme, its bio-based production has been explored [10]. While E. coli can be extensively engineered for enhanced heme biosynthesis, the overproduced heme is hard to secrete and tends to accumulate intracellularly, resulting in physiological toxicity to the production host and, therefore, limited production yield [11,12]. Such technical limitation prompted us to look for alternative porphyrins that could be extracellularly secreted for overproduction in E. coli.…”