Bloody bread - Serratia marcescens in action

The prodiginines are a family of red tri

pyrrole Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4 H4 NH. It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., ''N''-meth ...

dyestuff A dye is a colored substance that chemically bonds to the substrate to which it is being applied. This distinguishes dyes from pigments which do not chemically bind to the material they color. Dye is generally applied in an aqueous solution and ...

s produced by

Gammaproteobacteria Gammaproteobacteria is a class of bacteria in the phylum Pseudomonadota (synonym Proteobacteria). It contains about 250 genera, which makes it the most genera-rich taxon of the Prokaryotes. Several medically, ecologically, and scientifically imp ...

(e.g. ''

Serratia marcescens ''Serratia marcescens'' () is a species of rod-shaped, Gram-negative bacteria in the family Yersiniaceae. It is a facultative anaerobe and an opportunistic pathogen in humans. It was discovered in 1819 by Bartolomeo Bizio in Padua, Italy.Serrati ...

'') as well as some

Actinomycetota The ''Actinomycetota'' (or ''Actinobacteria'') are a phylum of all gram-positive bacteria. They can be terrestrial or aquatic. They are of great economic importance to humans because agriculture and forests depend on their contributions to soi ...

(e.g. ''

Streptomyces coelicolor ''Streptomyces albidoflavus'' is a bacterium species from the genus of ''Streptomyces'' which has been isolated from soil from Poland. ''Streptomyces albidoflavus'' produces dibutyl phthalate and streptothricins. Small noncoding RNA Bacteri ...

''). The group is named after

prodigiosin Prodigiosin is the red dyestuff produced by many strains of the bacterium ''Serratia marcescens'', as well as other Gram-negative, gamma proteobacteria such as ''Vibrio psychroerythrus'' and ''Hahella chejuensis''. It is responsible for the pink t ...

(prodiginine) and is biosynthesized through a common set of enzymes. They are interesting due to their history and their varied

biological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...

Structural types

Prodigiosin colour.svg,

Prodigiosin Prodigiosin is the red dyestuff produced by many strains of the bacterium ''Serratia marcescens'', as well as other Gram-negative, gamma proteobacteria such as ''Vibrio psychroerythrus'' and ''Hahella chejuensis''. It is responsible for the pink t ...

Cycloprodigiosin.svg, Cycloprodigiosin Cyclononylprodigiosin.svg, Cyclononylprodigiosin Undecylprodigiosin coloured.svg,

Undecylprodigiosin Undecylprodigiosin is an alkaloid produced by some Actinomycetes bacteria. It is a member of the prodiginines group of natural products and has been investigated for potential antimalarial activity. Natural sources Undecylprodigiosin is a second ...

Butyl-meta-cycloheptylprodiginine.svg, Butyl-meta-cycloheptylprodiginine

Natural sources

The prodiginines are

secondary metabolite Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the norm ...

s originally noted in ''

Serratia ''Serratia'' is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria of the family Yersiniaceae. According to the List of Prokaryotic names with Standing Nomenclature (LPSN), there are currently 19 species of ''Serratia'' that ar ...

'' species, especially ''Serratia marcescens''. They are also found in

Actinomycetes The Actinomycetales is an order of Actinomycetota. A member of the order is often called an actinomycete. Actinomycetales are generally gram-positive and anaerobic and have mycelia in a filamentous and branching growth pattern. Some actinomycete ...

, for example ''

'' and some marine bacteria, including '' Hahella chejuensis'' and ''

Pseudoalteromonas denitrificans ''Pseudoalteromonas denitrificans'' is a marine bacterium Marine prokaryotes are marine bacteria and marine archaea. They are defined by their habitat as prokaryotes that live in marine environments, that is, in the saltwater of seas or o ...

''. Cyclononylprodigiosin was isolated from

Actinomadura The genus ''Actinomadura'' is one of four genera of Actinomycetota that belong to the family Thermomonosporaceae. It contains aerobic, Gram-positive, non-acid-fast, non-motile, chemo-organotrophic actinomycetes that produce well-developed, non- ...

species.

Production

Biosynthesis

The prodiginines are produced from a common intermediate,

tambjamine Tambjamines are a group of natural products that are structurally related to the prodiginines. They are enamine derivatives of 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde (MBC). Chemical structure Tambjamines are composed of two pyrrole rings with ...

aldehyde (also known as MBC, from its systematic name 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde). This contains two pyrrole rings built from

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

and

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

as shown in the blue-shaded pathway in Figure 1. The

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

is subsequently condensed with a third pyrrole to form prodigiosin (compound 16 in Figure 1), which is then further elaborated to cycloprodigiosin (compound 22 in Figure 1) and the other members of the chemical family.

Laboratory

Details of the first

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes ...

of the parent prodigiosin were published in 1962, confirming the chemical structure. As with the biosynthesis, the key intermediate was MBC. This aldehyde has subsequently been prepared by other methods and used to make many prodiginines.

Uses

Prodigiosin was considered for commercial production in 1823 to dye silk and wool but it has poor stability to light and the advent of synthetic alternatives cut short this application. The group has also been investigated for its pharmaceutical potential as anticancer, immunosuppressant, and antimalarial agents.

References

{{Reflist Pyrroles Streptomyces Pseudomonadota