Penicillium Rubens
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''Penicillium rubens'' is a species of fungus in the genus ''
Penicillium ''Penicillium'' () is a genus of ascomycetous fungi that is part of the mycobiome of many species and is of major importance in the natural environment, in food spoilage, and in food and drug production. Some members of the genus produce pe ...
'' and was the first species known to produce the antibiotic
penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
. It was first described by Philibert Melchior Joseph Ehi Biourge in 1923. For the discovery of penicillin from this species
Alexander Fleming Sir Alexander Fleming (6 August 1881 – 11 March 1955) was a Scottish physician and microbiologist, best known for discovering the world's first broadly effective antibiotic substance, which he named penicillin. His discovery in 1928 of w ...
shared the Nobel Prize in Physiology or Medicine in 1945. The original penicillin-producing type has been variously identified as '' Penicillium rubrum'', ''P. notatum'', and '' P. chrysogenum'' among others, but genomic comparison and phylogenetic analysis in 2011 resolved that it is ''P. rubens.'' It is the best source of penicillins and produces
benzylpenicillin Benzylpenicillin, also known as penicillin G (PenG) or BENPEN, and in military slang "Peanut Butter Shot" is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis ...
(G),
phenoxymethylpenicillin Phenoxymethylpenicillin, also known as penicillin V (PcV) and penicillin VK, is an antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for the treatment of strep throat, otitis media, and cellulitis. ...
(V) and octanoylpenicillin (K). It also produces other important bioactive compounds such as andrastin, chrysogine, fungisporin,
roquefortine Roquefortine C is a mycotoxin that belongs to a class of naturally occurring 2,5-diketopiperazines produced by various fungi, particularly species from the genus ''Penicillium''. It was first isolated from a strain of ''Penicillium roqueforti'', a ...
, and sorbicillins.


History

A French microbiologist Philibert Melchior Joseph Ehi Biourge was the first to describe ''P. rubens'' in 1923. The medicinal importance was discovered by Alexander Fleming, a physician at
St Mary's Hospital, London St Mary's Hospital is an NHS hospital in Paddington, in the City of Westminster, London, founded in 1845. Since the UK's first academic health science centre was created in 2008, it has been operated by Imperial College Healthcare NHS Trust, wh ...
. In September 1928, Fleming found that one of his bacterial cultures (of ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...
'') was contaminated with mould, and that the area around the mould inhibited bacterial growth. He gave the name penicillin for the purported antibacterial substance produced by the mould. After a series of experimental tests, he published his discovery in the June 1929 issue of the ''British Journal of Experimental Pathology.'' With the help of his colleague Charles J. La Touche, Fleming identified the fungus as ''Penicillium rubrum''. But
Charles Thom Charles Thom (November 11, 1872 – May 24, 1956) was an American microbiologist and mycology, mycologist. Born and raised in Illinois, he received his PhD from the University of Missouri, the first such degree awarded by that institution. He w ...
at the
U. S. Department of Agriculture The United States Department of Agriculture (USDA) is the United States federal executive departments, federal executive department responsible for developing and executing federal laws related to farming, forestry, rural economic development, ...
, Peoria, Illinois, compared the specimen with his collection of ''Penicillium'' species, and corrected the species as ''P. notatum.'' In his publication in 1931, he resolved that ''P. notatum'' was a member of ''P. chrysogenum'' species complex, which he had described in 1910. ''P. notatum'' was described by Swedish chemist Richard Westling in 1811. Thom adopted and popularised the use of ''P. chrysogenum.'' After discovery of other new species and taxonomic reexamination, three species, ''P. notatum'', ''P. meleagrinum,'' and ''P. cyaneofulvum'' were recognised as ''P. chrysogenum.'' The Seventeenth International Botanical Congress held in Vienna, Austria, in 2005 adopted the name ''P. chrysogenum'' as the conserved name (''
nomen conservandum Nomen may refer to: *Nomen (Roman name), the middle part of Ancient Roman names * Nomen (Ancient Egypt), the personal name of Ancient Egyptian pharaohs * Jaume Nomen (born 1960), Catalan astronomer *Nomen, Latin for a certain part of speech In gr ...
).'' Whole genome sequence and phylogenetic analysis, particularly using β-tubulin sequences, in 2011 showed that ''P. notatum'' is ''P. rubens,'' and that ''P. chrysogenum'' is a different species.


Biology

''P. rubens'' is a common fungus of indoor environment. Along with '' Cladosporium halotolerans'' and ''
Aspergillus niger ''Aspergillus niger'' is a mold classified within the ''Nigri'' section of the ''Aspergillus'' genus. The ''Aspergillus'' genus consists of common molds found throughout the environment within soil and water, on vegetation, in fecal matter, on de ...
,'' it is one of the nuisance moulds when humidity is high. It is the most resilient mould as it needs less water for growth and propagation. It has a soft and velvety surface. The spore-bearing filaments,
conidiophores A conidium ( ; ), sometimes termed an asexual chlamydospore or chlamydoconidium (), is an asexual, non-motile spore of a fungus. The word ''conidium'' comes from the Ancient Greek word for dust, ('). They are also called mitospores due to ...
are smooth and measure 200-300 µm in length. The hairy surface, penicilli are 8-12 µm long. The conidia are smooth-walled, ellipsoidal in shape, measuring 2.5-4.0 µm long, and are blue or bluish-green in colour. It exists in a number of strains, of which the most important are Fleming's strain (designated CBS 205.57 or NRRL 824 or IBT 30142) from which the first penicillin was discovered and the Wisconsin strain (NRRL1951) obtained from a
cantaloupe The cantaloupe, rockmelon (Australia and New Zealand, although cantaloupe is used in some states of Australia), sweet melon, or spanspek (Southern Africa) is a melon that is a variety of the muskmelon species (''Cucumis melo'') from the fami ...
in Peoria, Illinois, in 1944 and has been used for industrial production of penicillin G. The original Wisconsin strain itself has been produced in a variety of strains.


Genome

''P. rubens'' has four chromosomes. The genome of the Wisconsin strain has been most studied. The nuclear genome of 54-1255 strain, regarded as low-penicillin producer, has a size of 32.19 Mb. There are 13,653
open reading frames In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
(ORFs), including 592 probable
pseudogenes Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes are ...
and 116 truncated ORFs. Three genes, namely ''pcbAB, pcbC'', and ''penDE'' constitute the core sites for penicillin biosynthesis. They are distributed in clusters among other (ORFs) in a 58.8 kb region, on chromosome 2. ''pcbAB'' encodes an enzyme α-aminoadipoyl-L-cysteinyl-D-valine synthetase, ''pcbC'' encodes isopenicillinN (IPN) synthase, and ''penDE'', encoding acyl-CoA:isopenicillinN acyltransferase. The high penicillin-producing strain, NCPC10086, has slightly larger genome of 32.3 Mb, with about 13,290 protein-coding genes. There are at least 69 genes not present in 54-1255 strain. The gene ''Pch018g00010'' that codes for enzymes in glutathione metabolism is considered as the key factor in enhanced penicillin production of this strain. The mitochondrial genome consists of 31,790 bp and 17 ORFs. Enzymes synthesised from the nuclear genome are not sufficient for complete synthesis of penicillin. Enzymes of the final biosynthetic pathway such as acyl-CoA:isopenicillinN acyltransferase28 and phenylacetyl-CoA ligase are synthesised in separate cell organelles called microbodies (
peroxisomes A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen pero ...
). The peroxisome gene ''pex11'' is essential for controlling the amount of penicillin synthesis; the more the gene is activated ( expressed), the more the penicillins.


Uses

''P. rubens'' is the principal source of a class of antibiotics, penicillins. The species produces three such compounds,
benzylpenicillin Benzylpenicillin, also known as penicillin G (PenG) or BENPEN, and in military slang "Peanut Butter Shot" is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis ...
(G),
phenoxymethylpenicillin Phenoxymethylpenicillin, also known as penicillin V (PcV) and penicillin VK, is an antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for the treatment of strep throat, otitis media, and cellulitis. ...
(V) and octanoylpenicillin (K). Penicillin G is the first naturally occurring compound isolated and used as an antibiotic. It is also the source of
cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...
s.


References

{{Taxonbar, from=Q60969184 Fungi described in 1923 Penicillium Penicillins Medicinal fungi History of medicine History of pharmacy Antibiotics