Year

2018

Degree Name

Doctor of Philosophy

Department

School of Biological Sciences

Abstract

Arsenic (As) is one of the most toxic metalloids, as it is harmful to all organisms. The two most important oxidation states of inorganic arsenic in the environment are the pentavalent arsenate (As5+) and trivalent arsenite (As3+) of which the former is predominant in aerobic environments. Arsenite disrupts enzyme function, while arsenate obstructs phosphate uptake and utilisation. In response, living organisms have developed various mechanisms for As tolerance. Arsenate reduction is a key step in most of these strategies. In bacteria, the major pathway for arsenic detoxification is arsenite extrusion. The key enzyme of this pathway is cytoplasmic arsenate reductase (ArsC), which catalyses the chemical reactions required to reduce arsenate to arsenite. Arsenite is subsequently expelled from the cell. It is purported that other protein families may have similar functions or be involved.

The work presented here focused on the sequence diversity and function of bacterial arsenate reductases (ArsCs) and some related protein families. Based on a global genome sequence search, a total of 637 ArsC sequences with a broad distribution (421 species of 17 bacterial phyla) were collected. They were classified into four distinctive ArsC families: Trx/TrR, GSH/Grx, GSH/Trx and MSH/Mrx with six groups of signature motifs. The Trx/TrR family was the most abundant and could be divided into three subfamilies based on distance between the two key cysteines in the catalytic motif CXnC (CX3C, CX6C and CX7C). This distinctive variation and other characters resulted in the formation of three separate clusters on the phylogenetic tree. Sequence and phylogenetic analyses suggested that the Trx/TrR, GSH/Trx and MSH/Mrx families may share an ancient ancestor or have undergone interchange during evolution. Some correlations between certain ArsC families/groupings and taxonomy groupings were also observed. In addition, a number of ars operons bearing multiple arsCs have been regconised in Proteobacteria and Actinobacteria exhibiting certain co-existences between different arsC family members. Interestingly, a considerable proportion of ArsCs were found in fusion with the ArsR regulator protein.

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.