Penicillium chrysogenum

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Penicillium chrysogenum
Penicillium notatum.jpg
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Eukaryota
Kingdom: Fungi
Division: Ascomycota
Class: Eurotiomycetes
Order: Eurotiales
Family: Aspergillaceae
Genus: Penicillium
Species:
P. chrysogenum
Binomial name
Penicillium chrysogenum
Thom (1910)

Penicillium chrysogenum (formerly known as Penicillium notatum) 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, [1] but it is mostly found in indoor environments, especially in damp or water-damaged buildings. [2] It has been recognised as a species complex that includes P. notatum, P. meleagrinum, and P. cyaneofulvum. [3] 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. [4] [5] It has rarely been reported as a cause of human disease. [6] It is the source of several β-lactam antibiotics, most significantly penicillin. Other secondary metabolites of P. chrysogenum include roquefortine C, meleagrin, [7] chrysogine, [8] 6-MSA [9] YWA1/melanin, [10] andrastatin A, [11] fungisporin, [12] secalonic acids, sorbicillin, [13] [14] and PR-toxin. [15]

Contents

Like the many other species of the genus Penicillium , P. chrysogenum usually reproduces by forming dry chains of spores (or conidia) from brush-shaped conidiophores. The conidia are typically carried by air currents to new colonisation sites. In P. chrysogenum, the conidia are blue to blue-green, and the mold sometimes exudes a yellow pigment. However, P. chrysogenum cannot be identified based on colour alone. Observations of morphology and microscopic features are needed to confirm its identity and DNA sequencing is essential to distinguish it from closely related species such as P. rubens. The sexual stage of P. chrysogenum was discovered in 2013 by mating cultures in the dark on oatmeal agar supplemented with biotin, after the mating types (MAT1-1 or MAT1-2) of the strains had been determined using PCR amplification. [16]

The airborne asexual spores of P. chrysogenum are important human allergens. Vacuolar and alkaline serine proteases have been implicated as the major allergenic proteins. [17]

P. chrysogenum has been used industrially to produce penicillin and xanthocillin X, to treat pulp mill waste, and to produce the enzymes polyamine oxidase, phosphogluconate dehydrogenase, and glucose oxidase. [15] [18]

Science

The discovery of penicillin ushered in a new age of antibiotics derived from microorganisms. Penicillin is an antibiotic isolated from growing Penicillium mold in a fermenter. The mold is grown in a liquid culture containing sugar and other nutrients including a source of nitrogen. As the mold grows, it uses up the sugar and starts to make penicillin only after using up most of the nutrients for growth.

History

Genetics and evolution

The ability to produce penicillin appears to have evolved over millions of years, and is shared with several other related fungi. It is believed to confer a selective advantage during competition with bacteria for food sources.[ citation needed ] Some bacteria have consequently developed the counter-ability to survive penicillin exposure by producing penicillinases, enzymes that degrade penicillin.[ citation needed ] Penicillinase production is one mechanism by which bacteria can become penicillin resistant.

The principal genes responsible for producing penicillin, pcbAB, pcbC, and penDE are closely linked, forming a cluster on chromosome I. [19] Some high-producing Penicillium chrysogenum strains used for the industrial production of penicillin contain multiple tandem copies of the penicillin gene cluster. [20]

Similar to other filamentous fungi, CRISPR/Cas9-mediated genome editing techniques are available for editing the genome of Penicillium chrysogenum. [21]

Related Research Articles

<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>Talaromyces marneffei</i> Species of fungus

Talaromyces marneffei, formerly called Penicillium marneffei, was identified in 1956. The organism is endemic to southeast Asia where it is an important cause of opportunistic infections in those with HIV/AIDS-related immunodeficiency. Incidence of T. marneffei infections has increased due to a rise in HIV infection rates in the region.

<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.

<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.

<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.

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

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. 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 (G), phenoxymethylpenicillin (V) and octanoylpenicillin (K). It also produces other important bioactive compounds such as andrastin, chrysogine, fungisporin, roquefortine, and sorbicillins.

<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 allii-sativi is a fungus species of the genus Penicillium, section Chrysogena. It is one of several Penicillium species that can produce penicillin in culture. The fungus has been found in Argentina, Bulgaria, France, Portugal, South Africa, and the United Kingdom. The specific epithet allii-sativi refers to the garlic plant, Allium sativum, from which the fungus was isolated.

Penicillium dipodomyis is a species of the genus of Penicillium which occurs in kangaroo rats and produces penicillin and the diketopiperazine dipodazine.

Penicillium flavigenum is a species of the genus of Penicillium which produces penitrem A, penicillin and roquefortine C.

Penicillium goetzii is a species of the genus of ascomycetous fungi.

Penicillium nordicum is an anamorph species of fungus in the genus Penicillium which produces ochratoxin A. Penicillium nordicum contaminates protein rich foods and foods with high NaCl-konzentration. It is mostly found on dry-cured meat products and cheese products

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 tardochrysogenum is a filamentous species of fungus in the genus Penicillium which produces penicillin, secalonic acids D and secalonic acids F.

Aspergillus viridinutans is a species of fungus in the genus Aspergillus. The species was first isolated in Frankston, Victoria, Australia and described in 1954. It is from the Fumigati section of Aspergillus. Several fungi from this section produce heat-resistant ascospores, and the isolates from this section are frequently obtained from locations where natural fires have previously occurred. A. viridinutans has been identified as the cause of chronic aspergillosis. The mycotoxin viriditoxin was first identified in A. viridinutans. A draft genome sequence of the strain derived from the original species description has been generated.

Aspergillus microthecius is a species of fungus in the genus Aspergillus. It is from the Nidulantes section. The species was first described in 1985. It has been reported to produce asperthecin, averufin, 7-methoxyaverufin, sterigmatocystin, versicolourin, desferritriacetylfusigen, echinocandin B, echinocandin E, emericellin, emestrin, aurantioemestrin, dethiosecoemestrin Emindol DA, microperfuranone, penicillin G, quadrilineatin, and sterigmatocystin.

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

Fungisporin is a antibiotic with the molecular formula C28H36N4O4 which is produced by Aspergillus and Penicillium species. The cyclic peptide is a tetramer, consists of one each of the two enantiomeric forms of phenylalanine and of valine.

References

  1. ↑ Samson RA, Houbraken J, Thrane U, Frisvad JC, Andersen B (2010). Food and Indoor Fungi. Utrecht, the Netherlands: CBS-KNAW- Fungal Biodiversity Centre. pp. 1–398.
  2. ↑ Andersen B, Frisvad JC, Søndergaard I, Rasmussen IS, Larsen LS (June 2011). "Associations between fungal species and water-damaged building materials". Appl. Environ. Microbiol. 77 (12): 4180–8. Bibcode:2011ApEnM..77.4180A. doi:10.1128/AEM.02513-10. PMC   3131638 . PMID   21531835.
  3. ↑ Samson RA, Hadlok R, Stolk AC (1977). "A taxonomic study of the Penicillium chrysogenum series". Antonie van Leeuwenhoek. 43 (2): 169–75. doi:10.1007/BF00395671. PMID   413477. S2CID   41843432.
  4. ↑ Houbraken, Jos; Frisvad, Jens C.; Samson, Robert A. (2011). "Fleming's penicillin producing strain is not Penicillium chrysogenum but P. rubens". IMA Fungus. 2 (1): 87–95. doi:10.5598/imafungus.2011.02.01.12. PMC   3317369 . PMID   22679592.
  5. ↑ Houbraken, J.; Frisvad, J.C.; Seifert, K.A.; Overy, D.P.; Tuthill, D.M.; Valdez, J.G.; Samson, R.A. (2012-12-31). "New penicillin-producing Penicillium species and an overview of section Chrysogena". Persoonia - Molecular Phylogeny and Evolution of Fungi. 29 (1): 78–100. doi:10.3767/003158512X660571. PMC   3589797 . PMID   23606767.
  6. ↑ Lyratzopoulos, G.; Ellis, M.; Nerringer, R.; Denning, D. W. (October 2002). "Invasive infection due to penicillium species other than P. marneffei". The Journal of Infection. 45 (3): 184–195. doi:10.1053/jinf.2002.1056. ISSN   0163-4453. PMID   12387776.
  7. ↑ Ali H, Ries MI, Nijland JG, Lankhorst PP, Hankemeier T, Bovenberg RA, Vreeken RJ, Driessen AJ (2013-06-12). "A branched biosynthetic pathway is involved in production of roquefortine and related compounds in Penicillium chrysogenum". PLOS ONE. 8 (6): e65328. Bibcode:2013PLoSO...865328A. doi: 10.1371/journal.pone.0065328 . PMC   3680398 . PMID   23776469.
  8. ↑ Viggiano A, Salo O, Ali H, Szymanski W, Lankhorst PP, Nygård Y, Bovenberg RA, Driessen AJ (February 2018). "Pathway for the Biosynthesis of the Pigment Chrysogine by Penicillium chrysogenum". Applied and Environmental Microbiology. 84 (4). Bibcode:2018ApEnM..84E2246V. doi:10.1128/AEM.02246-17. PMC   5795073 . PMID   29196288.
  9. ↑ Guzmán-Chávez F, Zwahlen RD, Bovenberg RA, Driessen AJ (2018). "Penicillium chrysogenum as Cell Factory for Natural Products". Frontiers in Microbiology. 9: 2768. doi: 10.3389/fmicb.2018.02768 . PMC   6262359 . PMID   30524395.
  10. ↑ Guzman-Chavez F, Salo O, Samol M, Ries M, Kuipers J, Bovenberg RA, Vreeken RJ, Driessen AJ (October 2018). "Deregulation of secondary metabolism in a histone deacetylase mutant of Penicillium chrysogenum". MicrobiologyOpen. 7 (5): e00598. doi:10.1002/mbo3.598. PMC   6182556 . PMID   29575742.
  11. ↑ Matsuda Y, Awakawa T, Abe I (September 2013). "Reconstituted biosynthesis of fungal meroterpenoid andrastin A". Tetrahedron. 69 (38): 8199–8204. doi:10.1016/j.tet.2013.07.029.
  12. ↑ Ali H, Ries MI, Lankhorst PP, van der Hoeven RA, Schouten OL, Noga M, Hankemeier T, van Peij NN, Bovenberg RA, Vreeken RJ, Driessen AJ (2014-06-02). "A non-canonical NRPS is involved in the synthesis of fungisporin and related hydrophobic cyclic tetrapeptides in Penicillium chrysogenum". PLOS ONE. 9 (6): e98212. Bibcode:2014PLoSO...998212A. doi: 10.1371/journal.pone.0098212 . PMC   4041764 . PMID   24887561.
  13. ↑ Salo O, Guzmán-Chávez F, Ries MI, Lankhorst PP, Bovenberg RA, Vreeken RJ, Driessen AJ (July 2016). "Identification of a Polyketide Synthase Involved in Sorbicillin Biosynthesis by Penicillium chrysogenum". Applied and Environmental Microbiology. 82 (13): 3971–3978. Bibcode:2016ApEnM..82.3971S. doi:10.1128/AEM.00350-16. PMC   4907180 . PMID   27107123.
  14. ↑ Guzmán-Chávez F, Salo O, Nygård Y, Lankhorst PP, Bovenberg RA, Driessen AJ (July 2017). "Mechanism and regulation of sorbicillin biosynthesis by Penicillium chrysogenum". Microbial Biotechnology. 10 (4): 958–968. doi:10.1111/1751-7915.12736. PMC   5481523 . PMID   28618182.
  15. 1 2 de Hoog GS, Guarro J, Gené J, Figueras F (2000), Atlas of Clinical Fungi - 2nd Edition, Centraalbureau voor Schimmelcultures (Utrecht)
  16. ↑ Böhm J, Hoff B, O'Gorman CM, Wolfers S, Klix V, Binger D, Zadra I, Kürnsteiner H, Pöggeler S, Dyer PS, Kück U (January 2013). "Sexual reproduction and mating-type-mediated strain development in the penicillin-producing fungus Penicillium chrysogenum". Proceedings of the National Academy of Sciences of the United States of America. 110 (4): 1476–81. doi: 10.1073/pnas.1217943110 . PMC   3557024 . PMID   23307807.
  17. ↑ Shen HD, Chou H, Tam MF, Chang CY, Lai HY, Wang SR (October 2003). "Molecular and immunological characterization of Pen ch 18, the vacuolar serine protease major allergen of Penicillium chrysogenum". Allergy. 58 (10): 993–1002. doi:10.1034/j.1398-9995.2003.00107.x. PMID   14510716. S2CID   28229046.
  18. ↑ Raper KB, Thom C (1949). A manual of the Penicillia. Williams & Wilkins Company (Baltimore).
  19. ↑ Martín JF, Gutiérrez S, Fernández FJ, Velasco J, Fierro F, Marcos AT, Kosalkova K (1994). "Expression of genes and processing of enzymes for the biosynthesis of penicillins and cephalosporins". Antonie van Leeuwenhoek. 65 (3): 227–43. doi:10.1007/BF00871951. PMID   7847890. S2CID   25327312.
  20. ↑ Fierro F, Barredo JL, Díez B, Gutierrez S, Fernández FJ, Martín JF (June 1995). "The penicillin gene cluster is amplified in tandem repeats linked by conserved hexanucleotide sequences". Proceedings of the National Academy of Sciences of the United States of America. 92 (13): 6200–4. Bibcode:1995PNAS...92.6200F. doi: 10.1073/pnas.92.13.6200 . PMC   41670 . PMID   7597101.
  21. ↑ Pohl C, Kiel JA, Driessen AJ, Bovenberg RA, Nygård Y (July 2016). "CRISPR/Cas9 Based Genome Editing of Penicillium chrysogenum". ACS Synthetic Biology. 5 (7): 754–64. doi:10.1021/acssynbio.6b00082. PMID   27072635. S2CID   206764457.
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