Penicillium rubens

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Penicillium rubens
Penicillium rubens (type specimen).png
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Eukaryota
Kingdom: Fungi
Division: Ascomycota
Class: Eurotiomycetes
Order: Eurotiales
Family: Aspergillaceae
Genus: Penicillium
Species:
P. rubens
Binomial name
Penicillium rubens
Biourge (1910)

Penicillium rubens is a species of fungus in the genus Penicillium and was the first species known to produce the antibiotic penicillin. It was first described by Philibert Melchior Joseph Ehi Biourge in 1923. For the discovery of penicillin from this species Alexander Fleming shared the Nobel Prize in Physiology or Medicine in 1945. [1] 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. [2] [3] It is the best source of penicillins and produces benzylpenicillin (G), phenoxymethylpenicillin (V) and octanoylpenicillin (K). It also produces other important bioactive compounds such as andrastin, chrysogine, fungisporin, roquefortine, and sorbicillins. [4] [5]

Contents

History

Belgian microbiologist Philibert Melchior Joseph Ehi Biourge was the first to describe P. rubens in 1923. [6] The medicinal importance was discovered by Alexander Fleming, a physician at St Mary's Hospital, London. In September 1928, Fleming found that one of his bacterial cultures (of Staphylococcus aureus ) 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. [7] With the help of his colleague Charles J. La Touche, Fleming identified the fungus as Penicillium rubrum. [1]

But Charles Thom at the U. S. Department of Agriculture, 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. [8] P. notatum was described by Swedish chemist Richard Westling in 1811. Thom adopted and popularised the use of P. chrysogenum. [9] After discovery of other new species and taxonomic reexamination, three species, P. notatum, P. meleagrinum, and P. cyaneofulvum were recognised as P. chrysogenum. [10] [11] The Seventeenth International Botanical Congress held in Vienna, Austria, in 2005 adopted the name P. chrysogenum as the conserved name ( nomen conservandum). [12]

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. [2] [13]

Biology

Penicillium rubens (CBS 205.57 = NRRL 824 = IBT 30142), Fleming's original penicillin-producer. A-C. Colonies seven-day-old 25degC. A. Colonies in Czapek yeast extract agar. B. Colonies in malt extract agar. C. Colonies in yeast extract sucrose agar. D-H. Conidiophores. I. Conidia. Bars = 10 um. Penicillium rubens (Fleming's strain).png
Penicillium rubens (CBS 205.57 = NRRL 824 = IBT 30142), Fleming's original penicillin-producer. A–C. Colonies seven-day-old 25°C. A. Colonies in Czapek yeast extract agar. B. Colonies in malt extract agar. C. Colonies in yeast extract sucrose agar. D–H. Conidiophores. I. Conidia. Bars = 10 µm.

P. rubens is a common fungus of indoor environment. Along with Cladosporium halotolerans and Aspergillus niger, 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. [14] It has a soft and velvety surface. The spore-bearing filaments, conidiophores 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. [15] 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 in Peoria, Illinois, in 1944 and has been used for industrial production of penicillin G. [16] The original Wisconsin strain itself has been produced in a variety of strains. [17]

Genome

P. rubens has four chromosomes. [18] 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 (ORFs), including 592 probable pseudogenes and 116 truncated ORFs. [19] 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, [20] on chromosome 2. [18] [17] pcbAB encodes an enzyme α-aminoadipoyl-L-cysteinyl-D-valine synthetase, pcbC encodes isopenicillinN (IPN) synthase, and penDE, encoding acyl-CoA:isopenicillinN acyltransferase. [21] 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. [22]

The mitochondrial genome consists of 31,790 bp and 17 ORFs. [19] 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). The peroxisome gene pex11 is essential for controlling the amount of penicillin synthesis; the more the gene is activated (expressed), the more the penicillins. [23]

Uses

P. rubens is the principal source of a class of antibiotics, penicillins. The species produces three such compounds, benzylpenicillin (G), phenoxymethylpenicillin (V) and octanoylpenicillin (K). [24] Penicillin G is the first naturally occurring compound isolated and used as an antibiotic. [25] [26] [27] It is also the source of cephalosporins. [28]

Related Research Articles

<span class="mw-page-title-main">Antibiotic</span> Antimicrobial substance active against bacteria

An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the ones which cause the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.

<span class="mw-page-title-main">Alexander Fleming</span> Scottish physician and biologist (1881–1955)

Sir Alexander Fleming 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 what was later named benzylpenicillin from the mould Penicillium rubens has been described as the "single greatest victory ever achieved over disease". For this discovery, he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Boris Chain.

<span class="mw-page-title-main">Penicillin</span> Group of antibiotics derived from Penicillium fungi

Penicillins 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 deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G and penicillin V. Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for different bacterial infections, though many types of bacteria have developed resistance following extensive use.

<span class="mw-page-title-main">Mold</span> Wooly, dust-like fungal structure or substance

A mold or mould is one of the structures that certain fungi can form. The dust-like, colored appearance of molds is due to the formation of spores containing fungal secondary metabolites. The spores are the dispersal units of the fungi. Not all fungi form molds. Some fungi form mushrooms; others grow as single cells and are called microfungi.

<span class="mw-page-title-main">Beta-lactam antibiotics</span> Class of broad-spectrum antibiotics

β-lactam antibiotics are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and carbacephems. Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Until 2003, when measured by sales, more than half of all commercially available antibiotics in use were β-lactam compounds. The first β-lactam antibiotic discovered, penicillin, was isolated from a strain of Penicillium rubens.

<i>Penicillium</i> Genus of fungi

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.

<i>Streptomyces</i> Genus of bacteria

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.

<i>Penicillium roqueforti</i> Species of fungus

Penicillium roqueforti is a common saprotrophic fungus in the genus Penicillium. Widespread in nature, it can be isolated from soil, decaying organic matter, and plants.

<i>Penicillium camemberti</i> Species of fungus

Penicillium camemberti is a species of fungus in the genus Penicillium. It is used in the production of Camembert, Brie, Langres, Coulommiers, and Cambozola cheeses, on which colonies of P. camemberti form a hard, white crust. It is responsible for giving these cheeses their distinctive flavors. An allergy to the antibiotic penicillin does not necessarily imply an allergy to cheeses made using P. camemberti.

<span class="mw-page-title-main">History of penicillin</span> Aspect of medical history

The history of penicillin follows observations and discoveries of evidence of antibiotic activity of the mould Penicillium that led to the development of penicillins that became the first widely used antibiotics. Following the production of a relatively pure compound in 1942, penicillin was the first naturally-derived antibiotic.

<span class="mw-page-title-main">Phenoxymethylpenicillin</span> Antibiotic medication

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. It is also used to prevent rheumatic fever and to prevent infections following removal of the spleen. It is given by mouth.

In enzymology, an isopenicillin N N-acyltransferase (EC 2.3.1.164) is an enzyme that catalyzes the chemical reaction

mecA is a gene found in bacterial cells which allows them to be resistant to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics.

<span class="mw-page-title-main">Discovery of penicillin</span>

Ancient societies used moulds to treat infections, and in the following centuries many people observed the inhibition of bacterial growth by moulds. While working at St Mary's Hospital in London in 1928, Scottish physician Alexander Fleming was the first to experimentally determine that a Penicillium mould secretes an antibacterial substance, which he named "penicillin". The mould was found to be a variant of Penicillium notatum, a contaminant of a bacterial culture in his laboratory. The work on penicillin at St Mary's ended in 1929.

<i>Penicillium chrysogenum</i> Species of fungus

Penicillium chrysogenum is a species of fungus in the genus Penicillium. It is common in temperate and subtropical regions and can be found on salted food products, but it is mostly found in indoor environments, especially in damp or water-damaged buildings. It has been recognised as a species complex that includes P. notatum, P. meleagrinum, and P. cyaneofulvum. Molecular phylogeny has established that Alexander Fleming's first discovered penicillin producing strain is of a distinct species, P. rubens, and not of P. notatum. It has rarely been reported as a cause of human disease. It is the source of several β-lactam antibiotics, most significantly penicillin. Other secondary metabolites of P. chrysogenum include roquefortine C, meleagrin, chrysogine, 6-MSA YWA1/melanin, andrastatin A, fungisporin, secalonic acids, sorbicillin, and PR-toxin.

<span class="mw-page-title-main">Charles Thom</span> American icrobiologist and mycologist (1872–1956)

Charles Thom was an American microbiologist and mycologist. Born and raised in Illinois, he received his PhD from the University of Missouri, the first such degree awarded by that institution. He studied the microbiology of dairy products and soil fungi, and in particular researched the genera Aspergillus and Penicillium. His work influenced the establishment of standards for food handling and processing in the USA. He pioneered the use of culture media to grow microorganisms, and, with food chemist James N. Currie, developed a process to mass-produce citric acid using Aspergillus. Thom played an important role in the development of penicillin in World War II.

<span class="mw-page-title-main">Meleagrin</span> Chemical compound

Meleagrin and its derivatives such as oxaline are bio-active benzylisoquinoline alkaloids made by various species of Penicillium fungi. It is similar to other fungal alkaloids, such as Roquefortine C, which is made as an intermediate in the same biosynthetic pathway.

Penicillium nalgiovense is an anamorph species of the genus Penicillium with lipolytic and proteolytic activity, which was first isolated from ellischau cheese. This species produces dichlorodiaportin, diaportinol, and diaportinic acid Penicillium nalgiovense is used for the maturation of certain fermented salami varieties and ham. In this process it protects the meat from colonization by other molds and bacteria

Penicillium rubrum is a species of fungus in the genus Penicillium which produces kojic acid, mitorubrin, mitorubrinol, rubratoxin A, rubratoxin B rubralactone, rubramin and occurs in grain corn and soybeans. Penicillium rubrum is similar to the species Penicillium chrysogenum.

Penicillium commune is an indoor fungus belonging to the genus Penicillium. It is known as one of the most common fungi spoilage moulds on cheese. It also grows on and spoils other foods such as meat products and fat-containing products like nuts and margarine. Cyclopiazonic acid and regulovasine A and B are the most important mycotoxins produced by P. commune. The fungus is the only known species to be able to produce both penitrem A and roquefortine. Although this species does not produce penicillin, it has shown to have anti-pathogenic activity. There are no known plant, animal or human diseases caused by P. commune.

References

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