Penicillium chrysogenum: Difference between revisions

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===Higher order taxa===
===Higher order taxa===


Cellular organisms; Eukaryota; Fungi; Ascomycota; Eurotiomycetes; Eurotiales; Trichocomaceae; Penicillium
Cellular organisms; Eukaryota; Fungi; Ascomycota; Eurotiomycetes; Eurotiales; Trichocomaceae; Penicillium  
 
===Species===


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'''NCBI: Taxonomy [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=5076&lvl=3&keep=1&srchmode=1&unlock&mod=1#modif]'''
'''Microbewiki: Penicillium [http://microbewiki.kenyon.edu/index.php/Penecillium]'''
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===Species===


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'''NCBI: Genome [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=genome&Cmd=ShowDetailView&TermToSearch=18934]'''
'''NCBI: Taxonomy [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=5076&lvl=3&keep=1&srchmode=1&unlock&mod=1#modif]'''
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''Penicillium chrysogenum''
''Penicillium chrysogenum''
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==Description and significance==
==Description and significance==


Penicillium chrysogenum is a widely studied species of Penicillium and sometimes are also known as P. notatum, P. meleagrinum,or P. cyaneofulvum (3) though occasionally they are not synonymous.15  It plays a significant role in the medical community as an antibiotic because it can create penicillin which degrades gram positive bacteria by affecting lysis of their cell wall.2  It can also play a role as either a pathogen or allergen.1,9,10,11
''Penicillium chrysogenum'' is a widely studied species of ''Penicillium'' and is sometimes known as ''P. notatum'', ''P. meleagrinum'',or ''P. cyaneofulvum'' (3) though occasionally they are not synonymous.(15) It plays a significant role in the medical community as an antibiotic because it can create penicillin which inhibits the biosynthesis of bacterial cell walls affecting lysis of the cell.(2) It can also play a role as either a pathogen (1),(9),(10), an allergen (11), and may aid in protecting crops from certain pathogenic attacks.(7)


Penicillium was originally discovered by Alexander Fleming.  Fleming observed that staphylococcus cultures which had been left on the lab bench and allowed to grow, had began to lyze and that the active factor could be extracted by filtration of the mold.  He described Penicillium as a fungal colony that begins as a “white fluffy mass” that later turns green then black.  A yellow color appears after several days that will diffuse throughout the medium.2
Penicillium was originally discovered by Alexander Fleming.  Fleming observed that staphylococcus cultures which had been left on the lab bench and allowed to grow, had begun to lyze and that the active factor could be extracted by filtration of the mold.  He described Penicillium as a fungal colony that begins as a “white fluffy mass” that later turns green then black.  A yellow color appears after several days that will diffuse throughout the medium.(2)


Penicillium chrysogenum is a common fungus that can inhabit a wide variety of habitats including the soils of degraded forests (4), on the pollen and provisions of alfalfa leafcutter bees (5), and in Arctic subglacial ice where they feed on sediment-rich basal ice shelves(6). Penicillium chrysogenum is most commonly found naturally in moist soils with plentiful quantities of carbon and nitrogen for miccohrizal growth.  This species can also be found on fruit causing decay. (8)
''Penicillium chrysogenum'' is a common fungus that can inhabit a wide variety of habitats including the soils of degraded forests (4), on the pollen and provisions of alfalfa leafcutter bees (5), and in Arctic subglacial ice where they feed on sediment-rich basal ice shelves.(6)  ''Penicillium chrysogenum'' is most commonly found naturally in moist soils with plentiful quantities of carbon and nitrogen for miccohrizal growth.  This species can also be found on fruit causing decay.(8)


The importance of sequencing the genome of Penicillium chrysogenum is evident; it is a major player in the lives of humans today in various forms; pathogen, allergen, and an industrial source of antibiotics.  Therefore understanding the various metabolic and biosynthetic systems of Penicillium chrysogenum will allow researchers the ability to limit growth when it acts as a pathogen, lower the allergic response to it when it acts as an allergen, or maximize biosynthesis of penicillin when it is used to make the antibiotic.  Additionally it is important to have the genome sequence of this species for analysis when considering the emergence of new drug resistant strains of bacteria.
The importance of sequencing the genome of ''Penicillium chrysogenum'' is evident; it is a major player in the lives of humans today in various forms; pathogen, allergen, and, most importantly, as an industrial source of antibiotics.  Therefore understanding the various metabolic and biosynthetic systems of ''Penicillium chrysogenum'' will allow researchers the ability to limit growth when it acts as a pathogen, lower the allergic response to it when it acts as an allergen, or maximize biosynthesis of penicillin when it is used to make the antibiotic.  Additionally, it is important to have the genome sequence of this species for analysis when considering the emergence of new drug resistant strains of bacteria.


==Genome structure==
==Genome structure==


There are four chromosomes in Penicillium chrysogenum and it has a genome size of 34.1Mb.14 Though Penicillium chrysogenum can contain plasmids, the key feature to Penicillium chrysogenum is not contained in a plasmid. The penicillin gene cluster is located on chromosome I for and is 10.4 Mb in size.  The genome has three genes which encode for the for the penicillin biosynthetic pathway, pcbAB, pcbC, and pcbDE which form a single gene cluster.  This gene sequence is important to the lifestyle of this species due to the interactions it has with other microbes such as streptococcus.  Without this sequence Penicillium chrysogenum would have far more competition from these microbes.  The other three chromosomes are 9.6, 7.6, and 6.3 Mb in size for II, III, and IV respectively.(15)
There are four chromosomes in ''Penicillium chrysogenum'' and collectively they have a genome size of 34.1Mb.(14) The penicillin gene cluster is located on chromosome I and is 10.4 Mb in size.  Chromosome I has three genes which encode for the penicillin biosynthetic pathway, pcbAB, pcbC, and pcbDE which form a single gene cluster.  This gene sequence is important to the lifestyle of this species due to the interactions it has with other microbes such as streptococcus.  Without this sequence Penicillium chrysogenum would have far more competition from these microbes.  The other three chromosomes are 9.6, 7.6, and 6.3 Mb in size for chromosomes II, III, and IV respectively.(15)
 
Many other partial sequences exist for ''Penicillium chrysogenum'' including sequences coding for sulfate uptake which requires genes sutA and sutB (16) and anthranilate synthesis by trpC.(17)  No full genome sequence exists as of Febuary 2006 for ''Penicillium chrysogenum''.(22)


Many other partial sequences exist for Penicillium chrysogenum including sequences coding for sulfate uptake which requires genes sutA and sutB (16) and anthranilate synthesis by trpC. (17)
''Penicillium chrysogenum'' may also contain plasmids.  Autonomously replicating plasmids that induce cotransformation have been helpful in the commercial exploitation of ''Penicillium chrysogenum'' as a penicillin maker.  These plasmids can aid in the over-expression of genes, cloning of genes, and disruption of genes.(21)


==Cell structure and metabolism==
==Cell structure and metabolism==
Describe any interesting features and/or cell structures; how it gains energy; what important molecules it produces.
 
''Penicillium chrysogenum'' exhibits typical eukaryotic cell structure; it has a tubulin cytoskeleton which is used for motility and cell structure, a mitochondira that produces ATP via the TCA cycle, etc.(22)
 
Figure 1 shows a high magnification image produced with scanning electron microscopy of the external cell structure of ''Penicillium chrysogenum''.  This image displays the typical filamentous hyphae that contain many conidia.  The oblong structures in the image are conidia, the asexual spores of the fungus.(23)  These conidia are the cause of pathogenicity in humans as in the cases of allergy and endophthalmitis.  The conidia originate from complexes known as conidiophores.  The growth of conidiophores begins when a stalk sprouts out of a foot cell.  The stalk swells at the end and forms a vesicle.  Sterigmata form from the vesicle which give way to long chains of conidia.(24)
 
[[Image:Figure 1.PNG|thumb|Description]]
 
An interesting aspect of the metabolism of ''Penicillium chrysogenum'' is that it will express metabolic genes differentially when grown in different medium.  Preferential gene expression shuts-down secondary metabolic pathways such as the expression of Isopenicillin N synthase through PacC (P08703 gene).(22)  The inactivation of PacC will also inactivate the production of conidia.(24)  In a glucose medium this gene is shut off while in lactose the gene is active.(22) 
 
''Penicillium chrysogenum'' has more defenses than penicillin, it has proteins that provide resistance to Fluconazole (Fluconazole resistance protein 1, P38124 gene) and cycloheximide (Cycloheximide resistance protein, P32071 gene).(22)


==Pathology==
==Pathology==


Penicillium chrysogenum is rarely pathogenic except in exceptional circumstances such as people with severely suppressed immune systems, like those with human immunodeficiency virus (HIV).  Due to this low pathogenicity, it is difficult to diagnose due to a low level of suspicion of infection.  Symptoms however include pulmonary infection including pneumonia, localized granulomas, fungus balls, and systemic infection.  Once diagnosed, infection is treated with the surgical removal of foci of infection and the use of an oral antifungal regiment, usually either amphotericin B or itraconazole.  Prognosis is poor for this type of infection.  Penicillium chrysogenum is usually not a cause of infection in people with normally functioning immune systems.(1)
''Penicillium chrysogenum'' is rarely pathogenic except in extenuating circumstances such as people with severely suppressed immune systems, like those with human immunodeficiency virus (HIV).  Due to low pathogenicity, it is difficult to diagnose given low levels of suspicion for infection.  Symptoms of infection include pulmonary infection including pneumonia, localized granulomas, fungus balls, and systemic infection.  Once diagnosed, infection is treated with the surgical removal of foci of infection and the use of an oral antifungal regiment, usually either amphotericin B or itraconazole.  Prognosis is poor for this type of infection.  ''Penicillium chrysogenum'' is usually not a cause of infection in people with normally functioning immune systems.(1)


Another such exceptional circumstance is in the case of endophthalmitis which is described as an inflammation of the ocular cavity.  The most common avenue for the implementation of infection by Penicillium chrysogenum in the eye is by penetrating trauma.  The infection is treated as a systemic infection would be, with an oral antifungal regiment, usually either amphotericin B or itraconazole with the caveat that a topical antifungal may also be prescribed. (9),(10)
Another such exceptional circumstance is in the case of endophthalmitis which is described as an inflammation of the ocular cavity.  The most common avenue for the implementation of infection by ''Penicillium chrysogenum'' in the eye is by penetrating trauma.  The infection is treated as a systemic infection would be, with an oral antifungal regiment, usually either amphotericin B or itraconazole with the caveat that a topical antifungal may also be prescribed.(9),(10)


Penicillium chrysogenum can also act as an allergen and an asthma inducer.  Pen ch 13 is the active allergen that triggers histamine responses in the epithelial cells of lungs.  The constriction of the airway ensues and the characteristic hack of the asthmatic is the most common symptom.  The exact mechanisms for crossing of the allergen into the epithelial cells is an active area of research.(12)
''Penicillium chrysogenum'' can also act as an allergen and an asthma inducer.  Pen ch 13 is the active allergen that triggers histamine responses in the epithelial cells of lungs.  The constriction of the airway ensues and the characteristic hack of the asthmatic is the most common symptom.  The exact mechanism for how the allergen crosses into the epithelial cells is an active area of research.(12)


==Application to Biotechnology==
==Application to Biotechnology==


Penicillium chrysogenum is usually exploited for its antibiotic capabilities.  It produces the hydrophobic β-lactam compound penicillin.  The efficacy of the specific penicillin made is dependent on its side chain.  Originally Penicillium chrysogenum was limited to the treatment of scarlet fever, pneumonia, gonorrhea, infections on wounds, and serious staphylococcal infections as Penicillian G.(13)  Today many variations of side chains yield a wide variety of semi-synthetic penicillin’s that are able to fight a broader range of bacteria however Penicillium chrysogenum remains the primary producer of Penicilian G and Penicilian V.(14)
''Penicillium chrysogenum'' is usually exploited for its antibiotic capabilities.  It produces the hydrophobic β-lactam compound penicillin.  The efficacy of the specific penicillin made is dependent on its side chain shown in Figure 2 as the R group.  Originally ''Penicillium chrysogenum'' was limited to the treatment of scarlet fever, pneumonia, gonorrhea, infection of wounds, and serious staphylococcal infections with Penicillian G.(13)  Today many variations of side chains yield a wide variety of semi-synthetic penicillins that are able to fight a broader range of bacteria; however, ''Penicillium chrysogenum'' remains the primary producer of Penicilian G and Penicilian V.(14)


The most common application of Penicillium chrysogenum is as an industrial producer of antibiotics. However it also has recently been suggested that Penicillium chrysogenum can be used to assist crops to fight off other pathogenic species.  The application of penicillin to crops such as apple trees, grapevines and tomatoes can induce their defense mechanisms and thereby help protect against apple scab, mildew, and early blite respectively in each of these crops.  This response is induced under greenhouse and field conditions and is not due to direct pathogenic effects from penicillin.(7)
[[Image:Figure 2.PNG|thumb|Description]]
 
It has been suggested that ''Penicillium chrysogenum'' can be used to assist crops to fight off other pathogenic species.  The application of penicillin to crops such as apple trees, grapevines and tomatoes can induce their defense mechanisms and thereby help protect against apple scab, mildew, and early blite respectively in each of these crops.  This response has been induced under greenhouse and field conditions and is not due to direct pathogenic effects from penicillin.(7)


==Current Research==
==Current Research==


The search for a complete understanding of the biosynthetic pathways for the production of penicillin in Penicillium chrysogenum is still an active area of research.  It is important to understand exactly how these pathways function to maximize the industrial processes for creating penicillin.  Currently there is no understanding as to how exactly iso-penicillin N (IPN) makes it into peroxisomes.  It has been found that other species that secrete IPN have ABC coupled transport as in the case of Aspergillus nidulans.  No such transporters exist in Penicillium chrysogenum.(18)
The search for a complete understanding of the biosynthetic pathways for the production of penicillin in ''Penicillium chrysogenum'' is still an active area of research.  It is important to understand exactly how these pathways function to maximize the industrial processes for creating penicillin.  Currently there is no understanding as to how exactly iso-penicillin N (IPN) makes it into peroxisomes.  It has been found that other species that secrete IPN have ABC coupled transport as in the case of ''Aspergillus nidulans''.  No such transporters exist in ''Penicillium chrysogenum''.(18)


Quit a lot is known about the antibiotic properties of Penicillium chrysogenum however little is known regarding the antifungal properties it contains.  Penicillium Antifungal Protein or PAF is a protein which inhibits the growth of certain taxonomically related filamentous fungi.  PAF may also affect the permeability of the membranes of filamentous fungi by catalyzing the leaking of potassium out of the cells.  Not all fungi are affected by it however and the exact action of PAF on cells is not none.(19)
Quit a lot is known about the antibiotic properties of ''Penicillium chrysogenum''; however, little is known regarding the antifungal properties it contains.  Penicillium Antifungal Protein (PAF) is a protein which inhibits the growth of certain taxonomically related filamentous fungi.  PAF may also affect the permeability of the membranes of filamentous fungi by catalyzing the leaking of potassium out of the cells.  Not all fungi are affected by it and the exact mechinism of action of PAF on cells is unknown.(19)


Amylases have been some of the most important enzymes in the eyes of humans for thousands of years.  They are a required work horse in the processes of alcoholic fermentation.  Because of their importance, they have been subject to industrial production.  Therefore new cost effective ways for producing amylases are studied.  One way to produce α-amylase (one of two types of amylases) is by Solid State Fermentation (SSF) which is a process that exposes an insoluble substrate to moisture but not standing water for fermentation.  Cheap agricultural by-products such as wheat bran and sunflower oil meal in combination have been fermented with Penicillium chrysogenum which produces α-amylase.  This is a low cost way to produce the product however large scale experiments are needed to ensure industrial application.(20)
Amylases have been some of the most important enzymes in the eyes of humans for thousands of years.  They are a required work horse in the processes of alcoholic fermentation.  Because of their importance, they have been subject to industrial production.  Therefore new cost effective ways for producing amylases are studied.  One way to produce α-amylase (one of two types of amylases) is by Solid State Fermentation (SSF) which is a process that exposes an insoluble substrate to moisture but not standing water for fermentation.  Cheap agricultural by-products such as wheat bran and sunflower oil meal in combination have been fermented with ''Penicillium chrysogenum'' which produces α-amylase.  This is a low cost way to produce the product; however, large scale experiments are needed to ensure industrial application.(20)


==References==
==References==
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http://www.springerlink.com/content/n8m5266050067r11/fulltext.pdf
http://www.springerlink.com/content/n8m5266050067r11/fulltext.pdf


7. Thuerig, B., Binder, A., Boller, T., et al. "An aqueous extract of the dry mycelium of Penicillium chrysogenum induces resistance in several crops under controlled and field conditions".  European Journal of Plant Pathology. Febuary 2006. Vol 114. Pages 185-197.
7. Thuerig, B., Binder, A., Boller, T., et al. "An aqueous extract of the dry mycelium of Penicillium chrysogenum induces resistance in several crops under controlled and field conditions".  European Journal of Plant Pathology. Febuary 2006. Vol 114. Pages 185-197.  
 
http://springerlink.metapress.com/content/x6x28h52507857m1/fulltext.pdf


8. Barkai-Golan, R. "Species of Penicillium causing decay of stored fruit in Isreal".  Mycopathologia. October 1974. Vol 54. Pages 141-145.
8. Barkai-Golan, R. "Species of Penicillium causing decay of stored fruit in Isreal".  Mycopathologia. October 1974. Vol 54. Pages 141-145.
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11. Shen, H.D., Chou, H., Tam, M.F., et al. “Molecular and immunological characterization of Pen ch 18, the vacuolar serine protease major allergen of Penicillium chrysogenum” Allergy. 2003 Oct;58(10):993-1002
11. Shen, H.D., Chou, H., Tam, M.F., et al. “Molecular and immunological characterization of Pen ch 18, the vacuolar serine protease major allergen of Penicillium chrysogenum” Allergy. 2003 Oct;58(10):993-1002
http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed&cmd=Retrieve&list_uids=14510716
http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed&cmd=Retrieve&list_uids=14510716


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http://nar.oxfordjournals.org/cgi/screenpdf/33/5/e50
http://nar.oxfordjournals.org/cgi/screenpdf/33/5/e50


15.  Fierro, F., Gutierrez, S., Diez, B., et al. “Reolution 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 I 10.4 Mb) in Penicillium chrysogenum”. MGG. January 1993. Vol 241. Pages 573-578
15.  Fierro, F., Gutierrez, S., Diez, B., et al. “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 I 10.4 Mb) in Penicillium chrysogenum”. MGG. January 1993. Vol 241. Pages 573-578
 
http://springerlink.metapress.com/content/hp01726x273w0577/fulltext.pdf


16. Mart van de Kamp, Pizzinini, E., Vos, A., et al. “Sulfate Transport in Penicillium chrysogenum: Cloning and Characterization of the sutA and sutB Genes”.  Journal of Bacteriology.  September 1999.  Vol 23. Pages 7228-7234.
16. Mart van de Kamp, Pizzinini, E., Vos, A., et al. “Sulfate Transport in Penicillium chrysogenum: Cloning and Characterization of the sutA and sutB Genes”.  Journal of Bacteriology.  September 1999.  Vol 23. Pages 7228-7234.
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http://springerlink.metapress.com/content/n38l520546786176/fulltext.pdf
http://springerlink.metapress.com/content/n38l520546786176/fulltext.pdf
21.  Bañuelos, O., Naranjo, L., Casqueiro, J., et al. “Co-transformation with autonomous replicating and integrative plasmids in Penicillium chrysogenum is highly efficient and leads in some cases to rescue of the intact integrative plasmid”.  Fungal Genetics and Biology.  November 2003.  Pages 83-92.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WFV-493HK83-1&_user=4429&_coverDate=11%2F30%2F2003&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000059602&_version=1&_urlVersion=0&_userid=4429&md5=ce584b1a4ce33d06bf0e65a7489a7869#toc17
22.  Castillo, N.I.,Fierro, F., Gutiérrez, S., et al. “Genome-wide analysis of differentially expressed genes from Penicillium chrysogenum grown with a repressing or a non-repressing carbon source”.  Current Genetics. Febuary 2006. Vol 49.  Pages 85-96.
http://www.springerlink.com/content/f1394783l02p7045/fulltext.pdf
23.  Ito, Y., Nozawa, Y., Setoguti, T.  “Examination of several selected fungi by scanning electron microscope”. Mycopathologia et Mycologia applicata.  1970. Vol 41. Pages 299-305.
http://www.springerlink.com/content/ww0x48q4763765u7/fulltext.pdf
24.  Calvo, A.M., Wilson, R.A., Bok, J.W. “Relationship between secondary metabolism and fungal development”.  September 2002. Vol 66. Pages 447-459.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=120793
Edited by: Kathryn Carlton,  Cathleen Carlton, Dr. Andrew Carlton.
Edited by KLB

Latest revision as of 03:27, 20 August 2010

This student page has not been curated.

A Microbial Biorealm page on the genus Penicillium chrysogenum

Classification

Higher order taxa

Cellular organisms; Eukaryota; Fungi; Ascomycota; Eurotiomycetes; Eurotiales; Trichocomaceae; Penicillium

Microbewiki: Penicillium [1]

Species

NCBI: Taxonomy [2]

Penicillium chrysogenum

Description and significance

Penicillium chrysogenum is a widely studied species of Penicillium and is sometimes known as P. notatum, P. meleagrinum,or P. cyaneofulvum (3) though occasionally they are not synonymous.(15) It plays a significant role in the medical community as an antibiotic because it can create penicillin which inhibits the biosynthesis of bacterial cell walls affecting lysis of the cell.(2) It can also play a role as either a pathogen (1),(9),(10), an allergen (11), and may aid in protecting crops from certain pathogenic attacks.(7)

Penicillium was originally discovered by Alexander Fleming. Fleming observed that staphylococcus cultures which had been left on the lab bench and allowed to grow, had begun to lyze and that the active factor could be extracted by filtration of the mold. He described Penicillium as a fungal colony that begins as a “white fluffy mass” that later turns green then black. A yellow color appears after several days that will diffuse throughout the medium.(2)

Penicillium chrysogenum is a common fungus that can inhabit a wide variety of habitats including the soils of degraded forests (4), on the pollen and provisions of alfalfa leafcutter bees (5), and in Arctic subglacial ice where they feed on sediment-rich basal ice shelves.(6) Penicillium chrysogenum is most commonly found naturally in moist soils with plentiful quantities of carbon and nitrogen for miccohrizal growth. This species can also be found on fruit causing decay.(8)

The importance of sequencing the genome of Penicillium chrysogenum is evident; it is a major player in the lives of humans today in various forms; pathogen, allergen, and, most importantly, as an industrial source of antibiotics. Therefore understanding the various metabolic and biosynthetic systems of Penicillium chrysogenum will allow researchers the ability to limit growth when it acts as a pathogen, lower the allergic response to it when it acts as an allergen, or maximize biosynthesis of penicillin when it is used to make the antibiotic. Additionally, it is important to have the genome sequence of this species for analysis when considering the emergence of new drug resistant strains of bacteria.

Genome structure

There are four chromosomes in Penicillium chrysogenum and collectively they have a genome size of 34.1Mb.(14) The penicillin gene cluster is located on chromosome I and is 10.4 Mb in size. Chromosome I has three genes which encode for the penicillin biosynthetic pathway, pcbAB, pcbC, and pcbDE which form a single gene cluster. This gene sequence is important to the lifestyle of this species due to the interactions it has with other microbes such as streptococcus. Without this sequence Penicillium chrysogenum would have far more competition from these microbes. The other three chromosomes are 9.6, 7.6, and 6.3 Mb in size for chromosomes II, III, and IV respectively.(15)

Many other partial sequences exist for Penicillium chrysogenum including sequences coding for sulfate uptake which requires genes sutA and sutB (16) and anthranilate synthesis by trpC.(17) No full genome sequence exists as of Febuary 2006 for Penicillium chrysogenum.(22)

Penicillium chrysogenum may also contain plasmids. Autonomously replicating plasmids that induce cotransformation have been helpful in the commercial exploitation of Penicillium chrysogenum as a penicillin maker. These plasmids can aid in the over-expression of genes, cloning of genes, and disruption of genes.(21)

Cell structure and metabolism

Penicillium chrysogenum exhibits typical eukaryotic cell structure; it has a tubulin cytoskeleton which is used for motility and cell structure, a mitochondira that produces ATP via the TCA cycle, etc.(22)

Figure 1 shows a high magnification image produced with scanning electron microscopy of the external cell structure of Penicillium chrysogenum. This image displays the typical filamentous hyphae that contain many conidia. The oblong structures in the image are conidia, the asexual spores of the fungus.(23) These conidia are the cause of pathogenicity in humans as in the cases of allergy and endophthalmitis. The conidia originate from complexes known as conidiophores. The growth of conidiophores begins when a stalk sprouts out of a foot cell. The stalk swells at the end and forms a vesicle. Sterigmata form from the vesicle which give way to long chains of conidia.(24)

Description

An interesting aspect of the metabolism of Penicillium chrysogenum is that it will express metabolic genes differentially when grown in different medium. Preferential gene expression shuts-down secondary metabolic pathways such as the expression of Isopenicillin N synthase through PacC (P08703 gene).(22) The inactivation of PacC will also inactivate the production of conidia.(24) In a glucose medium this gene is shut off while in lactose the gene is active.(22)

Penicillium chrysogenum has more defenses than penicillin, it has proteins that provide resistance to Fluconazole (Fluconazole resistance protein 1, P38124 gene) and cycloheximide (Cycloheximide resistance protein, P32071 gene).(22)

Pathology

Penicillium chrysogenum is rarely pathogenic except in extenuating circumstances such as people with severely suppressed immune systems, like those with human immunodeficiency virus (HIV). Due to low pathogenicity, it is difficult to diagnose given low levels of suspicion for infection. Symptoms of infection include pulmonary infection including pneumonia, localized granulomas, fungus balls, and systemic infection. Once diagnosed, infection is treated with the surgical removal of foci of infection and the use of an oral antifungal regiment, usually either amphotericin B or itraconazole. Prognosis is poor for this type of infection. Penicillium chrysogenum is usually not a cause of infection in people with normally functioning immune systems.(1)

Another such exceptional circumstance is in the case of endophthalmitis which is described as an inflammation of the ocular cavity. The most common avenue for the implementation of infection by Penicillium chrysogenum in the eye is by penetrating trauma. The infection is treated as a systemic infection would be, with an oral antifungal regiment, usually either amphotericin B or itraconazole with the caveat that a topical antifungal may also be prescribed.(9),(10)

Penicillium chrysogenum can also act as an allergen and an asthma inducer. Pen ch 13 is the active allergen that triggers histamine responses in the epithelial cells of lungs. The constriction of the airway ensues and the characteristic hack of the asthmatic is the most common symptom. The exact mechanism for how the allergen crosses into the epithelial cells is an active area of research.(12)

Application to Biotechnology

Penicillium chrysogenum is usually exploited for its antibiotic capabilities. It produces the hydrophobic β-lactam compound penicillin. The efficacy of the specific penicillin made is dependent on its side chain shown in Figure 2 as the R group. Originally Penicillium chrysogenum was limited to the treatment of scarlet fever, pneumonia, gonorrhea, infection of wounds, and serious staphylococcal infections with Penicillian G.(13) Today many variations of side chains yield a wide variety of semi-synthetic penicillins that are able to fight a broader range of bacteria; however, Penicillium chrysogenum remains the primary producer of Penicilian G and Penicilian V.(14)

Description

It has been suggested that Penicillium chrysogenum can be used to assist crops to fight off other pathogenic species. The application of penicillin to crops such as apple trees, grapevines and tomatoes can induce their defense mechanisms and thereby help protect against apple scab, mildew, and early blite respectively in each of these crops. This response has been induced under greenhouse and field conditions and is not due to direct pathogenic effects from penicillin.(7)

Current Research

The search for a complete understanding of the biosynthetic pathways for the production of penicillin in Penicillium chrysogenum is still an active area of research. It is important to understand exactly how these pathways function to maximize the industrial processes for creating penicillin. Currently there is no understanding as to how exactly iso-penicillin N (IPN) makes it into peroxisomes. It has been found that other species that secrete IPN have ABC coupled transport as in the case of Aspergillus nidulans. No such transporters exist in Penicillium chrysogenum.(18)

Quit a lot is known about the antibiotic properties of Penicillium chrysogenum; however, little is known regarding the antifungal properties it contains. Penicillium Antifungal Protein (PAF) is a protein which inhibits the growth of certain taxonomically related filamentous fungi. PAF may also affect the permeability of the membranes of filamentous fungi by catalyzing the leaking of potassium out of the cells. Not all fungi are affected by it and the exact mechinism of action of PAF on cells is unknown.(19)

Amylases have been some of the most important enzymes in the eyes of humans for thousands of years. They are a required work horse in the processes of alcoholic fermentation. Because of their importance, they have been subject to industrial production. Therefore new cost effective ways for producing amylases are studied. One way to produce α-amylase (one of two types of amylases) is by Solid State Fermentation (SSF) which is a process that exposes an insoluble substrate to moisture but not standing water for fermentation. Cheap agricultural by-products such as wheat bran and sunflower oil meal in combination have been fermented with Penicillium chrysogenum which produces α-amylase. This is a low cost way to produce the product; however, large scale experiments are needed to ensure industrial application.(20)

References

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Edited by: Kathryn Carlton, Cathleen Carlton, Dr. Andrew Carlton.

Edited by KLB