Biology:Penicillium rubens

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Short description: Species of fungus

Penicillium rubens
Penicillium rubens (type specimen).png
Scientific classification edit
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]

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 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]

References

  1. ↑ 1.0 1.1 Lalchhandama, K. (2020). "Reappraising Fleming's snot and mould". Science Vision 20 (1): 29–42. doi:10.33493/scivis.20.01.03. 
  2. ↑ 2.0 2.1 Houbraken, Jos; Frisvad, Jens C.; Samson, Robert A. (2011). "Fleming's penicillin producing strain is not Penicillium chrysogenum but P. rubens" (in en). IMA Fungus 2 (1): 87–95. doi:10.5598/imafungus.2011.02.01.12. PMID 22679592. 
  3. ↑ Hibbett, David S.; Taylor, John W. (2013). "Fungal systematics: is a new age of enlightenment at hand?" (in en). Nature Reviews Microbiology 11 (2): 129–133. doi:10.1038/nrmicro2963. PMID 23288349. https://www.nature.com/articles/nrmicro2963. 
  4. ↑ Visagie, C.M.; Houbraken, J.; Frisvad, J.C.; Hong, S.-B.; Klaassen, C.H.W.; Perrone, G.; Seifert, K.A.; Varga, J. et al. (2014). "Identification and nomenclature of the genus Penicillium" (in en). Studies in Mycology 78: 343–371. doi:10.1016/j.simyco.2014.09.001. PMID 25505353. 
  5. ↑ Pohl, Carsten; Polli, Fabiola; Schütze, Tabea; Viggiano, Annarita; Mózsik, László; Jung, Sascha; de Vries, Maaike; Bovenberg, Roel A. L. et al. (2020). "A Penicillium rubens platform strain for secondary metabolite production" (in en). Scientific Reports 10 (1): 7630. doi:10.1038/s41598-020-64893-6. PMID 32376967. Bibcode: 2020NatSR..10.7630P. 
  6. ↑ Biourge, P. (1923). "Les moissisures du groupe Penicillium Link". La Cellule 33: 7–331. http://www.mycobank.org/BioloMICS.aspx?TableKey=14682616000000061&Rec=11061. 
  7. ↑ Fleming, Alexander (1929). "On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to their Use in the Isolation of B. influenzæ". British Journal of Experimental Pathology 10 (3): 226–236. doi:10.1093/clinids/2.1.129. PMID 11545337. 
  8. ↑ "Appendix. History of species used and Dr. Thom's diagnoses of species" (in en). Philosophical Transactions of the Royal Society of London. Series B, Containing Papers of a Biological Character 220 (468–473): 83–92. 1931. doi:10.1098/rstb.1931.0015. 
  9. ↑ Thom, Charles (1945). "Mycology Presents Penicillin". Mycologia 37 (4): 460–475. doi:10.2307/3754632. 
  10. ↑ Samson, R. A.; Hadlok, R.; Stolk, Amelia C. (1977). "A taxonomic study of the Penicillium chrysogenum series" (in en). Antonie van Leeuwenhoek 43 (2): 169–175. doi:10.1007/BF00395671. PMID 413477. 
  11. ↑ Scott, James; Untereiner, Wendy A.; Wong, Bess; Straus, Neil A.; Malloch, David (2004). "Genotypic variation in Penicillium chysogenum from indoor environments". Mycologia 96 (5): 1095–1105. doi:10.1080/15572536.2005.11832908. PMID 21148929. 
  12. ↑ "International Code of Botanical Nomenclature (VIENNA CODE). Appendix IV Nomina specifica conservanda et rejicienda. B. Fungi". 2006. https://www.iapt-taxon.org/icbn/main.htm. 
  13. ↑ 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" (in en). Persoonia - Molecular Phylogeny and Evolution of Fungi 29 (1): 78–100. doi:10.3767/003158512X660571. PMID 23606767. 
  14. ↑ Segers, Frank J. J.; van Laarhoven, Karel A.; Huinink, Hendrik P.; Adan, Olaf C. G.; Wösten, Han A. B.; Dijksterhuis, Jan (2016). Brakhage, A. A.. ed. "The Indoor Fungus Cladosporium halotolerans Survives Humidity Dynamics Markedly Better than Aspergillus niger and Penicillium rubens despite Less Growth at Lowered Steady-State Water Activity" (in en). Applied and Environmental Microbiology 82 (17): 5089–5098. doi:10.1128/AEM.00510-16. PMID 27316968. Bibcode: 2016ApEnM..82.5089S. 
  15. ↑ "Penicillium rubens Biourge ATCC ® 28089™". https://www.atcc.org/products/all/28089.aspx#characteristics. 
  16. ↑ Raper, K. B.; Alexander, D. F.; Coghill, R. D. (1944). "Penicillin: II. Natural Variation and Penicillin Production in Penicillium notatum and Allied Species". Journal of Bacteriology 48 (6): 639–659. doi:10.1128/JB.48.6.639-659.1944. PMID 16560880. 
  17. ↑ 17.0 17.1 Martín, Juan F. (2020). "Insight into the Genome of Diverse Penicillium chrysogenum Strains: Specific Genes, Cluster Duplications and DNA Fragment Translocations" (in en). International Journal of Molecular Sciences 21 (11): 3936. doi:10.3390/ijms21113936. PMID 32486280. 
  18. ↑ 18.0 18.1 Fierro, Francisco; Gutiérrez, Santiago; Diez, Bruno; Martín, Juan F. (1993). "Resolution of four large chromosomes in penicillin-producing filamentous fungi: the penicillin gene cluster is located on chromosome II (9.6 Mb) in Penicillium notatum and chromosome 1 (10.4 Mb) in Penicillium chrysogenum" (in en). Molecular and General Genetics 241-241 (5–6): 573–578. doi:10.1007/BF00279899. PMID 8264531. 
  19. ↑ 19.0 19.1 van den Berg, Marco A; Albang, Richard; Albermann, Kaj; Badger, Jonathan H; Daran, Jean-Marc; M Driessen, Arnold J; Garcia-Estrada, Carlos; Fedorova, Natalie D et al. (2008). "Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum" (in en). Nature Biotechnology 26 (10): 1161–1168. doi:10.1038/nbt.1498. PMID 18820685. 
  20. ↑ Díez, B.; Gutiérrez, S.; Barredo, J. L.; van Solingen, P.; van der Voort, L. H.; Martín, J. F. (1990). "The cluster of penicillin biosynthetic genes. Identification and characterization of the pcbAB gene encoding the alpha-aminoadipyl-cysteinyl-valine synthetase and linkage to the pcbC and penDE genes". The Journal of Biological Chemistry 265 (27): 16358–16365. doi:10.1016/S0021-9258(17)46231-4. PMID 2129535. 
  21. ↑ Fierro, F.; Barredo, J. L.; Diez, B.; Gutierrez, S.; Fernandez, F. J.; Martin, J. F. (1995). "The penicillin gene cluster is amplified in tandem repeats linked by conserved hexanucleotide sequences." (in en). Proceedings of the National Academy of Sciences 92 (13): 6200–6204. doi:10.1073/pnas.92.13.6200. PMID 7597101. Bibcode: 1995PNAS...92.6200F. 
  22. ↑ Wang, Fu-Qiang; Zhong, Jun; Zhao, Ying; Xiao, Jingfa; Liu, Jing; Dai, Meng; Zheng, Guizhen; Zhang, Li et al. (2014). "Genome sequencing of high-penicillin producing industrial strain of Penicillium chrysogenum" (in en). BMC Genomics 15 (Suppl 1): S11. doi:10.1186/1471-2164-15-S1-S11. PMID 24564352. 
  23. ↑ Kiel, Jan A.K.W.; van der Klei, Ida J.; van den Berg, Marco A.; Bovenberg, Roel A.L.; Veenhuis, Marten (2005). "Overproduction of a single protein, Pc-Pex11p, results in 2-fold enhanced penicillin production by Penicillium chrysogenum" (in en). Fungal Genetics and Biology 42 (2): 154–164. doi:10.1016/j.fgb.2004.10.010. PMID 15670713. 
  24. ↑ Ferrero, M. A.; Reglero, A.; Martín-Villacorta, J.; Fernández-Cañón, J. M.; Luengo, J. M. (1990). "Biosynthesis of benzylpenicillin (G), phenoxymethylpenicillin (V) and octanoylpenicillin (K) from glutathione S-derivatives". The Journal of Antibiotics 43 (6): 684–691. doi:10.7164/antibiotics.43.684. PMID 2166024. 
  25. ↑ Winkle, Walton Van; Herwick, Robert P. (1945). "Penicillin—a review*" (in en). Journal of the American Pharmaceutical Association 34 (4): 97–109. doi:10.1002/jps.3030340402. 
  26. ↑ Lobanovska, Mariya; Pilla, Giulia (2017). "Penicillin's Discovery and Antibiotic Resistance: Lessons for the Future?". The Yale Journal of Biology and Medicine 90 (1): 135–145. PMID 28356901. 
  27. ↑ Bush, K (2004). "Antibacterial drug discovery in the 21st century" (in en). Clinical Microbiology and Infection 10: 10–17. doi:10.1111/j.1465-0691.2004.1005.x. PMID 15522035. 
  28. ↑ Cantwell, C. A.; Beckmann, R. J.; Dotzlaf, J. E.; Fisher, D. L.; Skatrud, P. L.; Yeh, W. K.; Queener, S. W. (1990). "Cloning and expression of a hybrid Streptomyces clavuligerus cefE gene in Penicillium chrysogenum". Current Genetics 17 (3): 213–221. doi:10.1007/BF00312612. PMID 2111228. 

Wikidata ☰ Q60969184 entry



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