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Penicillium rubens

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Penicillium rubens
Scientific classification Edit this classification
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

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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

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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

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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

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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

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  1. ^ a b Lalchhandama, K. (2020). "Reappraising Fleming's snot and mould". Science Vision. 20 (1): 29–42. doi:10.33493/scivis.20.01.03.
  2. ^ a b 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.
  3. ^ Hibbett, David S.; Taylor, John W. (2013). "Fungal systematics: is a new age of enlightenment at hand?". Nature Reviews Microbiology. 11 (2): 129–133. doi:10.1038/nrmicro2963. PMID 23288349. S2CID 17070407.
  4. ^ Visagie, C.M.; Houbraken, J.; Frisvad, J.C.; Hong, S.-B.; Klaassen, C.H.W.; Perrone, G.; Seifert, K.A.; Varga, J.; Yaguchi, T.; Samson, R.A. (2014). "Identification and nomenclature of the genus Penicillium". Studies in Mycology. 78: 343–371. doi:10.1016/j.simyco.2014.09.001. PMC 4261876. PMID 25505353.
  5. ^ Pohl, Carsten; Polli, Fabiola; Schütze, Tabea; Viggiano, Annarita; Mózsik, László; Jung, Sascha; de Vries, Maaike; Bovenberg, Roel A. L.; Meyer, Vera; Driessen, Arnold J. M. (2020). "A Penicillium rubens platform strain for secondary metabolite production". Scientific Reports. 10 (1): 7630. Bibcode:2020NatSR..10.7630P. doi:10.1038/s41598-020-64893-6. PMC 203126. PMID 32376967.
  6. ^ Biourge, P. (1923). "Les moissisures du groupe Penicillium Link". La Cellule. 33: 7–331.
  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. JSTOR 4452419. PMC 2048009. PMID 11545337.
  8. ^ "Appendix. History of species used and Dr. Thom's diagnoses of species". 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.
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  12. ^ "International Code of Botanical Nomenclature (VIENNA CODE). Appendix IV Nomina specifica conservanda et rejicienda. B. Fungi". International Association of Plant Taxonomy. 2006. Retrieved 17 June 2020.
  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". Persoonia - Molecular Phylogeny and Evolution of Fungi. 29 (1): 78–100. doi:10.3767/003158512X660571. PMC 3589797. 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". Applied and Environmental Microbiology. 82 (17): 5089–5098. Bibcode:2016ApEnM..82.5089S. doi:10.1128/AEM.00510-16. PMC 4988216. PMID 27316968.
  15. ^ "Penicillium rubens Biourge ATCC ® 28089™". www.atcc.org. Retrieved 2020-06-17.
  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. PMC 374019. PMID 16560880.
  17. ^ a b Martín, Juan F. (2020). "Insight into the Genome of Diverse Penicillium chrysogenum Strains: Specific Genes, Cluster Duplications and DNA Fragment Translocations". International Journal of Molecular Sciences. 21 (11): 3936. doi:10.3390/ijms21113936. PMC 7312703. PMID 32486280.
  18. ^ a b 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". Molecular and General Genetics. 241–241 (5–6): 573–578. doi:10.1007/BF00279899. PMID 8264531. S2CID 13542522.
  19. ^ a b 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; Harris, Diana M; Heijne, Wilbert H M; Joardar, Vinita (2008). "Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum". 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". Proceedings of the National Academy of Sciences. 92 (13): 6200–6204. Bibcode:1995PNAS...92.6200F. doi:10.1073/pnas.92.13.6200. PMC 41670. PMID 7597101.
  22. ^ Wang, Fu-Qiang; Zhong, Jun; Zhao, Ying; Xiao, Jingfa; Liu, Jing; Dai, Meng; Zheng, Guizhen; Zhang, Li; Yu, Jun; Wu, Jiayan; Duan, Baoling (2014). "Genome sequencing of high-penicillin producing industrial strain of Penicillium chrysogenum". BMC Genomics. 15 (Suppl 1): S11. doi:10.1186/1471-2164-15-S1-S11. PMC 4046689. 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". 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*". Journal of the American Pharmaceutical Association. 34 (4): 97–109. doi:10.1002/jps.3030340402. PMC 3802448.
  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. PMC 5369031. PMID 28356901.
  27. ^ Bush, K (2004). "Antibacterial drug discovery in the 21st century". 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. S2CID 9230950.