Understudied proteins and understudied functions in the model bacterium Bacillus subtilis—A major challenge in current research

Abstract

Model organisms such as the Gram-positive bacterium Bacillus subtilis have been studied intensively for decades. However, even for model organisms, no function has been identified for about one fourth of all proteins. It has recently been realized that such understudied proteins as well as poorly studied functions set a limitation to our understanding of the requirements for cellular life, and the Understudied Proteins Initiative has been launched. Of poorly studied proteins, those that are strongly expressed are likely to be important to the cell and should therefore be considered high priority in further studies. Since the functional analysis of unknown proteins can be extremely laborious, a minimal knowledge is required prior to targeted functional studies. In this review, we discuss strategies to obtain such a minimal annotation, for example, from global interaction, expression, or localization studies. We present a set of 41 highly expressed and poorly studied proteins of B. subtilis. Several of these proteins are thought or known to bind RNA and/or the ribosome, some may control the metabolism of B. subtilis, and another subset of particularly small proteins may act as regulatory elements to control the expression of downstream genes. Moreover, we discuss the challenges of poorly studied functions with a focus on RNA-binding proteins, amino acid transport, and the control of metabolic homeostasis. The identification of the functions of the selected proteins not only will strongly advance our knowledge on B. subtilis, but also on other organisms since many of the proteins are conserved in many groups of bacteria.

Control of iron homeostasis by a regulatory protein-protein interaction inBacillus subtilis: The FurA (YlaN) acts as an antirepressor to the ferric uptake regulator Fur

“…The FurA (YlaN) protein belongs to a small group of so far unknown proteins that are strongly expressed under essentially all conditions in B. subtilis (29). Of those about 40 proteins, FurA is the only that is essential under standard laboratory growth conditions (30, 35).…”

“…Although B. subtilis is one of the best studied bacteria, the function of many proteins remains to be elucidated. The YlaN protein a highly abundant but only poorly studied protein (28, 29). Moreover, the ylaN gene is essential under standard growth conditions (30, 31).…”

Coenzyme A biosynthesis inBacillus subtilis: Discovery of a novel precursor metabolite for salvage and its uptake system

“…This suggests that this ABC transporter may transport not only cystine, but also a precursor molecule that allows pantothenate-independent synthesis of coenzyme A. This idea is supported by the established promiscuity of many amino acid transporters (16,33,34). Candidates for such substrates are pantothenate or pantetheine which could be introduced into the either of the two pathways to CoaA (see above, Fig.…”

Control of three-carbon amino acid homeostasis by promiscuous importers and exporters inBacillus subtilis: Role of the sleeping beauty family of amino acid exporters

“…We have long-standing interest in the control of amino acid homeostasis in the model bacterium B. subtilis (5,19,25,26,27). Although B. subtilis is one of the best studied bacteria, the transporters for several amino acids as well as the substrates of several potential amino acid transporters have not yet been elucidated (24,28,29). With the exception of -aminobutyrate (30), the transport of non-proteogenic amino acids has not been studied in B. subtilis.…”