Penicillium chrysogenum

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,[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] but molecular phylogeny established that it is a distinct species and that P. notatum (its popular synonym) is P. rubens.[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]

Penicillium chrysogenum
Scientific classification
Kingdom: Fungi
Division: Ascomycota
Class: Eurotiomycetes
Order: Eurotiales
Family: Trichocomaceae
Genus: Penicillium
Species:
P. chrysogenum
Binomial name
Penicillium chrysogenum
Thom (1910)

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. Some bacteria have consequently developed the counter-ability to survive penicillin exposure by producing penicillinases, enzymes that degrade penicillin. 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-based genome editing techniques are available for editing the genome of Penicillium chrysogenum.[21]

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. 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.
  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). 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. 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. 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.
  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.
  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.
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