Bacillibactin is a catechol-based

siderophore Siderophores (Greek: "iron carrier") are small, high-affinity iron-chelating compounds that are secreted by microorganisms such as bacteria and fungi. They help the organism accumulate iron. Although a widening range of siderophore functions is no ...

secreted by members of the genus ''

Bacillus ''Bacillus'' (Latin "stick") is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum ''Bacillota'', with 266 named species. The term is also used to describe the shape (rod) of other so-shaped bacteria; and the plural ''Bacilli ...

'', including ''

Bacillus anthracis ''Bacillus anthracis'' is a gram-positive and rod-shaped bacterium that causes anthrax, a deadly disease to livestock and, occasionally, to humans. It is the only permanent ( obligate) pathogen within the genus ''Bacillus''. Its infection is a ...

'' and ''

Bacillus subtilis ''Bacillus subtilis'', known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus ''Bacillu ...

''. It is involved in the chelation of

ferric In chemistry, iron(III) refers to the element iron in its +3 oxidation state. In ionic compounds (salts), such an atom may occur as a separate cation (positive ion) denoted by Fe3+. The adjective ferric or the prefix ferri- is often used to spe ...

iron (Fe³⁺) from the surrounding environment and is subsequently transferred into the bacterial cytoplasm via the use of

ABC transporters The ATP synthase, ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene family, gene families. It is represented in all extant taxon, extant Phylum ...

Biosynthesis

The biosynthetic pathway of bacillibactin was first identified by May et al. in the

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bacte ...

B. subtilis ''Bacillus subtilis'', known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus ''Bacillu ...

''. The

is synthesized through multimodular non ribosomal peptide

synthetase In biochemistry, a ligase is an enzyme that can catalyze the joining (Ligation (molecular biology), ligation) of two large molecules by forming a new chemical bond. This is typically via hydrolysis of a small pendant chemical group on one of the ...

s (NRPS), similar to

enterobactin Enterobactin (also known as enterochelin) is a high affinity siderophore that acquires iron for microbial systems. It is primarily found in Gram-negative bacteria, such as ''Escherichia coli'' and '' Salmonella typhimurium''. Enterobactin is t ...

. However, unlike enterobactin, the genes responsible for encoding the bacillibactin synthetases are all located in one

operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...

. This gene cluster is termed ''dhb'' – cognate to the catecholic structure of 2,3-dihydroxybenzoate (DHB) – and it can be divided into the specific genes responsible for encoding the enzymes. The three genes are ''dhbE, dhbB,'' and ''dhbF'', which get translated into DhbE, DhbB, and DhbF synthetases. Notably, DhbF was characterized as a dimodular NRPS, unlike the monomodular EntF synthetase for enterobactin. The structure of bacillibactin consists of three 2,3-dihydroxybenzoate (DHB) groups attached to a cyclic amino acid core synthesized by multimodular NRPS. It is the condensation of three DHB-

Glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

Threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

units that ultimately leads to the formation of bacillibactin. In the first step of NRPS, the relevant amino acid is adenylated and transferred to the thiol group of the adjacent synthetases. DhbE is selective for DHB, DhbF1 is selective for glycine, and DhbF2 is selective for threonine. DHB is first adenylated by DhbE and transferred to DhbB's thiol group in the second step of NRPS. Once the relevant compounds are thiolated, the construction of bacillibactin begins. After DHB is transferred to DhbB, an adjacent synthetase orchestrates the condensation of DHB and glycine onto DhbF1. Then the DHB-Gly unit is further condensed onto the threonine unit on DhbF2, resulting in a DHB-Gly-Thr unit. This process is repeated twice more. However at the end of the third iteration, the hydroxyl group from the first threonine intramolecularly attacks the synthetase-ester bond to create the cyclic amino acid core for bacillibactin. : Bacillibactin 2

References

{{Reflist Depsipeptides Catechols Siderophores