Subsystem: Inorganic sulfur (sulfate) assimilation

Introduction Sulfur is required for the biosynthesis of several essential compounds like amino acids (cysteine and methionine), vitamins (biotin, thiamin), and prosthetic groups (Fe-S clusters) in all organisms. In order to synthesize these compounds, the sulfur has usually to be in a reduced state, most commonly as (hydrogen) sulfide. In the absence of an environmental supply of reduced sulfur moieties (e.g. a black smoker or another organism), organisms have to reduce the needed sulfur themselves. In many microorganisms this function is performed by a very common pathway for assimilatory sulfate reduction, leading from sulfate to sulfide, which is then incorporated in various sulfur containing metabolites (Fig. 1). Subsystem overview For each of the reaction steps there seem to exist at least two functional variants (Fig. 2) that appear to be only weakly correlated with each other, so that almost any combination can be found (Fig. 3). The first step in the pathway is the uptake of oxidized inorganic sulfur compounds, usually sulfate or thiosulfate. Several transporters are known to be involved in this, like the ABC-type transporter Sbp CysAWPT in Escherichia coli [1] or the Pit-type permease (SulP) in Bacillus subtilis [2]. Following uptake, intracellular sulfate is activated by adenylylation, yielding adenosine phosphosulfate (APS). Two different enzyme families of sulfate adenylyltransferase are commonly involved in this reaction: a heteromeric form (SAT1+2, usually called CysDN) known from E. coli; and the homomeric form (DSAT) described for example in B. subtilis [2], which is usually used in dissimilatory sulfate reduction [3]. The next step is the reduction of the activated sulfate. APS is either phosphorylated to phosphoadenosine phosphosulfate (PAPS) by APS kinase (ASK, CysC) and subsequently reduced to sulfite by PAPS reductase (PAPSR, CysH) or converted directly by APS reductase (APSR, also called CysH). Which way is used in particular is hard to determine by sequence similarity alone as APS and PAPS reductases belong to the same protein family and APS reductase has been shown to also act on PAPS [4,5,6]. If not verified experimentally, it should therefore be assumed that APS reductase is bifunctional in an organism if APS kinase is also present. The last step of the pathway is the conversion of sulfite to sulfide. In E. coli and B. subtilis this step is catalyzed by a heteromeric form of sulfite reductase (SIR FP+HP, CysIJ), using NADPH directly as an electron donor [1]. Interestingly, there are a lot of organisms where only the hemoprotein subunit (SIR HP) or a protein more similar to the ferredoxin-dependent sulfite and nitrite reductases known from plants is present. In the latter case, electrons for sulfite/nitrite reductase are derived either from the photosystem I or, in non-photosynthetic tissues, from NADPH [7]. These electrons are then transferred via an ferredoxin—NADPH reductase onto a ferredoxin that in turn delivers them to the homomeric form of sulfite reductase.