The prodiginines are a family of red tripyrrole dyestuffs produced by Gammaproteobacteria (e.g. Serratia marcescens ) as well as some Actinomycetota (e.g. Streptomyces coelicolor ). The group is named after prodigiosin (prodiginine) and is biosynthesized through a common set of enzymes. [1] They are interesting due to their history and their varied biological activity. [2]
The prodiginines are secondary metabolites originally noted in Serratia species, especially Serratia marcescens. They are also found in Actinomycetes, for example Streptomyces coelicolor and some marine bacteria, including Hahella chejuensis and Pseudoalteromonas denitrificans . Cyclononylprodigiosin was isolated from Actinomadura species. [2] [3]
The Prodiginine family consists of primarily red-pigmented tripyrrole secondary metabolites. [4]
 |  |
Prodiginine, first extracted from terrestrial Serratia marcescens, consisted of a straight alkyl chain substituent and was named prodigiosin. [5]
The prodiginines are produced from a common intermediate, tambjamine aldehyde (also known as MBC, from its systematic name 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde). This contains two pyrrole rings built from proline and serine as shown in the blue-shaded pathway in Figure 1. [1] The aldehyde is subsequently condensed with a third pyrrole to form prodigiosin [6] (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. [2] [7] [8]
Details of the first total synthesis of the parent prodigiosin were published in 1962, confirming the chemical structure. As with the biosynthesis, the key intermediate was MBC. [9] This aldehyde has subsequently been prepared by other methods and used to make many prodiginines. [8]
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. [8] The group has also been investigated for its pharmaceutical potential as anticancer, immunosuppressant, and antimalarial agents. [2] [3] [10]
Pyrrole is a heterocyclic, aromatic, organic compound, a five-membered ring with the formula C4H4NH. It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3. Porphobilinogen, a trisubstituted pyrrole, is the biosynthetic precursor to many natural products such as heme.
Porphyrins are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH−). In vertebrates, an essential member of the porphyrin group is heme, which is a component of hemoproteins, whose functions include carrying oxygen in the bloodstream. In plants, an essential porphyrin derivative is chlorophyll, which is involved in light harvesting and electron transfer in photosynthesis.
Serratia is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria of the family Enterobacteriaceae. According to the List of Prokaryotic names with Standing Nomenclature (LPSN), there are currently 19 species of Serratia that are credibly published with accurate names as of 2020: S. aquatilis, S. entomophila, S. ficaria, S. fonticola, S. grimesii, S. liquefaciens, S. marcescens, S. microhaemolytica, S. myotis, S. nematodiphila, S. odoriferae, S. oryzae, S. plymuthica, S. proteamaculans, S. quinivorans corrig, S. rubidaea, S. symbiotica, S. ureilytica, S. vespertilionis. They are typically 1–5 μm in length, do not produce spores, and can be found in water, soil, plants, and animals. Some members of this genus produce a characteristic red pigment, prodigiosin, and can be distinguished from other members of the order Enterobacterales by their unique production of three enzymes: DNase (nucA), lipase, and gelatinase (serralysin). Serratia was thought to be a harmless environmental bacteria until it was discovered that the most common species in the genus, S. marcescens, is an opportunistic pathogen of many animals, including humans. In humans, S. marcescens is mostly associated with nosocomial, or hospital-acquired, infections, but can also cause urinary tract infections, pneumonia, and endocarditis. S. marcescens is frequently found in showers, toilet bowls, and around wet tiles as a pinkish to red biofilm but only causes disease in immunocompromised individuals. Aside from S. marcescens, some rare strains of the Serratia species – S. plymuthica, S. liquefaciens, S. rubidaea, and S. odoriferae – have been shown to cause infection such as osteomyelitis and endocarditis.
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. S. marcescens is commonly involved in hospital-acquired infections (HAIs), also called nosocomial infections, particularly catheter-associated bacteremia, urinary tract infections, and wound infections, and is responsible for 1.4% of HAI cases in the United States. It is commonly found in the respiratory and urinary tracts of hospitalized adults and in the gastrointestinal systems of children.
Streptomyces is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of Streptomyces bacteria have been described. As with the other Actinomycetota, streptomycetes are gram-positive, and have very large genomes with high GC content. Found predominantly in soil and decaying vegetation, most streptomycetes produce spores, and are noted for their distinct "earthy" odor that results from production of a volatile metabolite, geosmin. Different strains of the same species may colonize very diverse environments.
In organic chemistry, polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone and methylene groups: [−C(=O)−CH2−]n. First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. Biotechnology has enabled discovery of more naturally-occurring polyketides and evolution of new polyketides with novel or improved bioactivity.
Kanamycin A, often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. It is not a first line treatment. It is used by mouth, injection into a vein, or injection into a muscle. Kanamycin is recommended for short-term use only, usually from 7 to 10 days. As with most antibiotics, it is ineffective in viral infections.
Formylation refers to any chemical processes in which a compound is functionalized with a formyl group (-CH=O). In organic chemistry, the term is most commonly used with regards to aromatic compounds. In biochemistry the reaction is catalysed by enzymes such as formyltransferases.
Prodigiosin is the red dye 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 tint occasionally found in grime that accumulates on porcelain surfaces such as bathtubs, sinks, and toilet bowls. It is in the prodiginine family of compounds which are produced in some Gram-negative gamma proteobacteria, as well as select Gram-positive Actinobacteria. The name prodigiosin is derived from prodigious.
Perosamine is a mannose-derived 4-aminodeoxysugar produced by some bacteria.
In enzymology, a [acyl-carrier-protein] S-malonyltransferase is an enzyme that catalyzes the chemical reaction
Clavams are a class of antibiotics. This antibiotic is derived from Streptomyces clavuligerus NRRL 3585. Clavam is produced to form a new β-lactam antibiotic. This class is divided into the clavulanic acid class and the 5S clavams class. Both groups are the outcomes of the fermentation process produced by Streptomyces spp. Clavulanic acid is a broad-spectrum antibiotic and 5S clavams may have anti-fungal properties. They are similar to penams, but with an oxygen substituted for the sulfur. Thus, they are also known as oxapenams.
In molecular biology, the polyketide synthesis cyclase family of proteins includes a number of cyclases involved in polyketide synthesis in a number of actinobacterial species.
Geosmin synthase or germacradienol-geosmin synthase designates a class of bifunctional enzymes that catalyze the conversion of farnesyl diphosphate (FPP) to geosmin, a volatile organic compound known for its earthy smell. The N-terminal half of the protein catalyzes the conversion of farnesyl diphosphate to germacradienol and germacrene D, followed by the C-terminal-mediated conversion of germacradienol to geosmin. The conversion of FPP to geosmin was previously thought to involve multiple enzymes in a biosynthetic pathway.
Oroidin is a bromopyrrole alkaloid, originally isolated from marine sponges in the genus Agelas. Its complex structure leads to wide biological activities, which makes Oroidin a potential drug candidate for various diseases. It also serves as chemical defense in marine sponges.
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).
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.
Streptomyces netropsis is a bacterium species from the genus of Streptomyces. Streptomyces netropsis produces the antibiotics netropsin and distamycin A and the antifungal polyene mycoheptin.
Pentabromopseudilin, the first reported marine microbial antibiotic, is a bioactive natural product that contains a highly halogenated 2-arrylpyrrole moiety. Pentabromopseudilin (PBP) is a unique hybrid bromophenol-bromopyrrole compound that is made up of over 70% bromine atoms, contributing to its potent bioactivity. PBP was first isolated from Pseudomonas bromoutilis, and has since been found to be produced by other marine microbes, including Alteromonas luteoviolaceus, Chromobacteria, and Pseudoalteromonas spp.
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.