Using Diatom and Apicomplexan Models to Study the Heme Pathway of Chromera velia

Abstract

Heme biosynthesis is essential for almost all living organisms. Despite its conserved function, the pathway’s enzymes can be located in a remarkable diversity of cellular compartments in different organisms. This location does not always reflect their evolutionary origins, as might be expected from the history of their acquisition through endosymbiosis. Instead, the final subcellular localization of the enzyme reflects multiple factors, including evolutionary origin, demand for the product, availability of the substrate, and mechanism of pathway regulation. The biosynthesis of heme in the apicomonad Chromera velia follows a chimeric pathway combining heme elements from the ancient algal symbiont and the host. Computational analyses using different algorithms predict complex targeting patterns, placing enzymes in the mitochondrion, plastid, endoplasmic reticulum, or the cytoplasm. We employed heterologous reporter gene expression in the apicomplexan parasite Toxoplasma gondii and the diatom Phaeodactylum tricornutum to experimentally test these predictions. 5-aminolevulinate synthase was located in the mitochondria in both transfection systems. In T. gondii, the two 5-aminolevulinate dehydratases were located in the cytosol, uroporphyrinogen synthase in the mitochondrion, and the two ferrochelatases in the plastid. In P. tricornutum, all remaining enzymes, from ALA-dehydratase to ferrochelatase, were placed either in the endoplasmic reticulum or in the periplastidial space.

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

“…The C5 pathway is the more common pathway of ALA synthesis in archaea, most bacteria, and plants. Compared to the C4 pathway, it is the more efficient and preferred pathway for heme manufacture in the industry due to its ability to obtain higher heme titers with a simple carbon source as a substrate [34][35][36]. In this pathway, there are three steps (Figure 2), glutamyl-tRNA is first obtained by transfer RNA (tRNA) binding to the five-carbon backbone of glutamate catalyzed by glutamyl-tRNA synthetase (gltX).…”

“…pathway for heme manufacture in the industry due to its ability to obtain higher heme titers with a simple carbon source as a substrate [34,35,36]. In this pathway, there are three steps (Figure 2), glutamyl-tRNA is first obtained by transfer RNA (tRNA) binding to the five-carbon backbone of glutamate catalyzed by glutamyl-tRNA synthetase (gltX).…”

Unlocking the richness of microalgae biodiversity for potential applications

“…and Helicosporidium sp. Although these microalgae lack genes related to photosynthesis in their plastids, the plastids still play a crucial role in their survival by participating in various biological pathways other than photosynthesis [40][41][42].…”

Efficient De Novo Biosynthesis of Heme by Membrane Engineering in Escherichia coli

“…The C5 pathway of heme biosynthesis is found in plants, most bacteria and archaea. Compared to the C4 pathway, the C5 pathway uses simple carbon sources with higher titer of heme as substrates; therefore, it is more suitable for the biosynthesis of heme in prokaryotes [ 20 , 21 , 22 , 23 ]. In the C5 pathway, glutamate was firstly catalyzed by glutamyl-tRNA synthetase ( gltX ) and generate glutamyl-tRNA.…”