Sulfurous gases as biological messengers and toxins: comparative genetics of their metabolism in model organisms

Abstract

Gasotransmitters are biologically produced gaseous signalling molecules. As gases with potent biological activities, they are toxic as air pollutants, and the sulfurous compounds are used as fumigants. Most investigations focus on medical aspects of gasotransmitter biology rather than toxicity toward invertebrate pests of agriculture. In fact, the pathways for the metabolism of sulfur containing gases in lower organisms have not yet been described. To address this deficit, we use protein sequences from Homo sapiens to query Genbank for homologous proteins in Caenorhabditis elegans, Drosophila melanogaster, and Saccharomyces cerevisiae. In C. elegans, we find genes for all mammalian pathways for synthesis and catabolism of the three sulfur containing gasotransmitters, H(2)S, SO(2) and COS. The genes for H(2)S synthesis have actually increased in number in C. elegans. Interestingly, D. melanogaster and Arthropoda in general, lack a gene for 3-mercaptopyruvate sulfurtransferase, an enzym for H(2)S synthesis under reducing conditions.

Figure 1

Metabolism of sulfur containing amino acids. (a) Homocysteine-dependent transsulfuration pathway that containing both cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). Which is located in the cytosol and generates hydrogen sulfide (H₂S). (b) H₂S synthesis via aspartate aminotransferase (AAT) and 3-mercaptopyruvate sulfurtransferase (3MST), which occurs in the cytosol and mitochondria. (c) Catabolism of cysteine via cysteine dioxygenase (CDO) and AAT generates sulfur dioxide (SO₂).

Figure 2

Phylogenetic tree analysis of cystathionine-β-synthase (CBS) and putative cysteine synthase (PCS). A blast (blastp) search of known Homo sapiens (H.s) proteins was undertaken against three different species, Saccharomyces cerevisiae (S.c), Drosophila melanogaster (D.m), and Caenorhabditis elegans (C.e) in the Genbank database. Identified sequences with significant expected value (≤1E−10) were used to generate a multiple sequence alignment (MSA) via ClustalW 2.1. The MSAs were then trimmed and used to produce an unrooted phylogenetic tree with 10,000 boostraps via Geneious 5.4.

Figure 3

Phylogenetic tree analysis of cystathionine-γ-lyase and Cystathionine-β-lyase (CBL). F22B8.6 (CTH-1/CSE-1), ZK1127.10 (CTH-2/CSE-2), and C12C8.2 (CBL). See Figure 2 for details on the phylogenetic analysis.

Figure 4

Phylogenetic tree analysis of 3-mercaptopyruvate sulfurtransferase (3MST/MPST). See Figure 2 for details on the phylogenetic analysis.

Figure 5

Phylogenetic tree analysis of aspartate aminotransferase (AAT/ASAT/AspAT/GOT (glutamic oxaloacetic transaminase)). See Figure 2 for details on the phylogenetic analysis.