scholarly journals The metabolism of 6-aminopenicillanic acid and related compounds by Penicillium chrysogenum and its possible significance for penicillin biosynthesis

1960 ◽  
Vol 76 (2) ◽  
pp. 375-381 ◽  
Author(s):  
Edith C. Wolff ◽  
H. R. V. Arnstein
1991 ◽  
Vol 10 (2) ◽  
pp. 489-495 ◽  
Author(s):  
W. H. Müller ◽  
T. P. van der Krift ◽  
A. J. Krouwer ◽  
H. A. Wösten ◽  
L. H. van der Voort ◽  
...  

1999 ◽  
Vol 181 (4) ◽  
pp. 1181-1188 ◽  
Author(s):  
Javier Casqueiro ◽  
Santiago Gutiérrez ◽  
Oscar Bañuelos ◽  
Maria Jose Hijarrubia ◽  
Juan Francisco Martín

ABSTRACT Two strategies have been used for targeted integration at thelys2 locus of Penicillium chrysogenum. In the first strategy the disruption of lys2 was obtained by a single crossing over between the endogenous lys2 and a fragment of the same gene located in an integrative plasmid.lys2-disrupted mutants were obtained with 1.6% efficiency when the lys2 homologous region was 4.9 kb, but no homologous integration was observed with constructions containing a shorter homologous region. Similarly,lys2-disrupted mutants were obtained by a double crossing over (gene replacement) with an efficiency of 0.14% by using two lys2 homologous regions of 4.3 and 3.0 kb flanking thepyrG marker. No homologous recombination was observed when the selectable marker was flanked by short lys2 homologous DNA fragments. The disruption of lys2 was confirmed by Southern blot analysis of three different lysine auxotrophs obtained by a single crossing over or gene replacement. Thelys2-disrupted mutants lacked α-aminoadipate reductase activity (encoded by lys2) and showed specific penicillin yields double those of the parental nondisrupted strain, Wis 54-1255. The α-aminoadipic acid precursor is channelled to penicillin biosynthesis by blocking the lysine biosynthesis branch at the α-aminoadipate reductase level.


Biochimie ◽  
2009 ◽  
Vol 91 (2) ◽  
pp. 214-225 ◽  
Author(s):  
Katarina Kosalková ◽  
Carlos García-Estrada ◽  
Ricardo V. Ullán ◽  
Ramiro P. Godio ◽  
Raúl Feltrer ◽  
...  

2010 ◽  
Vol 9 (8) ◽  
pp. 1236-1250 ◽  
Author(s):  
Birgit Hoff ◽  
Jens Kamerewerd ◽  
Claudia Sigl ◽  
Rudolf Mitterbauer ◽  
Ivo Zadra ◽  
...  

ABSTRACT Penicillium chrysogenum is the industrial producer of the antibiotic penicillin, whose biosynthetic regulation is barely understood. Here, we provide a functional analysis of two major homologues of the velvet complex in P. chrysogenum, which we have named P. chrysogenum velA (PcvelA) and PclaeA. Data from array analysis using a ΔPcvelA deletion strain indicate a significant role of PcVelA on the expression of biosynthesis and developmental genes, including PclaeA. Northern hybridization and high-performance liquid chromatography quantifications of penicillin titers clearly show that both PcVelA and PcLaeA play a major role in penicillin biosynthesis in a producer strain that underwent several rounds of UV mutagenesis during a strain improvement program. Both regulators are further involved in different developmental processes. While PcvelA deletion leads to light-independent conidial formation, dichotomous branching of hyphae, and pellet formation in shaking cultures, a ΔPclaeA strain shows a severe impairment in conidiophore formation under both light and dark conditions. Bimolecular fluorescence complementation assays provide evidence for a velvet-like complex in P. chrysogenum, with structurally conserved components that have distinct developmental roles, illustrating the functional plasticity of these regulators in genera other than Aspergillus.


1994 ◽  
Vol 40 (6) ◽  
pp. 883-887 ◽  
Author(s):  
Susanne Havn Eriksen ◽  
Bo Jensen ◽  
Ib Schneider ◽  
Svend Kaasgaard ◽  
Jørgen Olsen

2017 ◽  
Vol 84 (4) ◽  
Author(s):  
Annarita Viggiano ◽  
Oleksandr Salo ◽  
Hazrat Ali ◽  
Wiktor Szymanski ◽  
Peter P. Lankhorst ◽  
...  

ABSTRACT Chrysogine is a yellow pigment produced by Penicillium chrysogenum and other filamentous fungi. Although the pigment was first isolated in 1973, its biosynthetic pathway has so far not been resolved. Here, we show that deletion of the highly expressed nonribosomal peptide synthetase (NRPS) gene Pc21g12630 ( chyA ) resulted in a decrease in the production of chrysogine and 13 related compounds in the culture broth of P. chrysogenum . Each of the genes of the chyA -containing gene cluster was individually deleted, and corresponding mutants were examined by metabolic profiling in order to elucidate their function. The data suggest that the NRPS ChyA mediates the condensation of anthranilic acid and alanine into the intermediate 2-(2-aminopropanamido)benzoic acid, which was verified by feeding experiments of a ΔchyA strain with the chemically synthesized product. The remainder of the pathway is highly branched, yielding at least 13 chrysogine-related compounds. IMPORTANCE Penicillium chrysogenum is used in industry for the production of β-lactams, but also produces several other secondary metabolites. The yellow pigment chrysogine is one of the most abundant metabolites in the culture broth, next to β-lactams. Here, we have characterized the biosynthetic gene cluster involved in chrysogine production and elucidated a complex and highly branched biosynthetic pathway, assigning each of the chrysogine cluster genes to biosynthetic steps and metabolic intermediates. The work further unlocks the metabolic potential of filamentous fungi and the complexity of secondary metabolite pathways.


Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 712
Author(s):  
Carlos García-Estrada ◽  
Juan F. Martín ◽  
Laura Cueto ◽  
Carlos Barreiro

Penicillin biosynthesis by Penicillium chrysogenum is one of the best-characterized biological processes from the genetic, molecular, biochemical, and subcellular points of view. Several omics studies have been carried out in this filamentous fungus during the last decade, which have contributed to gathering a deep knowledge about the molecular mechanisms underlying improved productivity in industrial strains. The information provided by these studies is extremely useful for enhancing the production of penicillin or other bioactive secondary metabolites by means of Biotechnology or Synthetic Biology.


2010 ◽  
Vol 76 (17) ◽  
pp. 5702-5709 ◽  
Author(s):  
Wiebe H. Meijer ◽  
Loknath Gidijala ◽  
Susan Fekken ◽  
Jan A. K. W. Kiel ◽  
Marco A. van den Berg ◽  
...  

ABSTRACT In the fungus Penicillium chrysogenum, penicillin (PEN) production is compartmentalized in the cytosol and in peroxisomes. Here we show that intact peroxisomes that contain the two final enzymes of PEN biosynthesis, acyl coenzyme A (CoA):6-amino penicillanic acid acyltransferase (AT) as well as the side-chain precursor activation enzyme phenylacetyl CoA ligase (PCL), are crucial for efficient PEN synthesis. Moreover, increasing PEN titers are associated with increasing peroxisome numbers. However, not all conditions that result in enhanced peroxisome numbers simultaneously stimulate PEN production. We find that conditions that lead to peroxisome proliferation but simultaneously interfere with the normal physiology of the cell may be detrimental to antibiotic production. We furthermore show that peroxisomes develop in germinating conidiospores from reticule-like structures. During subsequent hyphal growth, peroxisome proliferation occurs at the tip of the growing hyphae, after which the organelles are distributed over newly formed subapical cells. We observed that the organelle proliferation machinery requires the dynamin-like protein Dnm1.


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