Characterization of the Gene Encoding S-adenosyl-L-methionine (AdoMet) Synthetase in Penicillium chrysogenum; Role in Secondary Metabolism and Penicillin Production

The filamentous fungus Penicillium chrysogenum (recently reidentified as Penicillium rubens) is used in the industrial production of the b-lactam antibiotic penicillin. There are several mechanisms regulating the production of this antibiotic, acting both at the genetic and epigenetic levels, the latter including the modification of chromatin by methyltransferases. S-adenosyl-L-methionine (AdoMet) is the main donor of methyl groups for methyltransferases. In addition, it also acts as a donor of aminopropyl groups during the biosynthesis of polyamines. AdoMet is synthesized from L-methionine and ATP by AdoMet-synthetase. In silico analysis of the P. chrysogenum genome revealed the presence of a single gene (Pc16g04380) encoding a putative protein with high similarity to well-known AdoMet-synthetases. Due to the essential nature of this gene, functional analysis was carried out using RNAi-mediated silencing techniques. Knock-down transformants exhibited a decrease in AdoMet, S-adenosyl-L-homocysteine (AdoHcy), spermidine and benzylpenicillin levels, whereas they accumulated a yellow-orange pigment in submerged cultures. On the other hand, overexpression led to reduced levels of benzylpenicillin, thereby suggesting that the AdoMet synthetase, in addition to participate in primary metabolism, also controls secondary metabolism in P. chrysogenum.

Download Full-text

Metabolite profiling during graft union formation reveals the reprogramming of primary metabolism and the induction of stilbene synthesis at the graft interface in grapevine

BMC Plant Biology ◽

10.1186/s12870-019-2055-9 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Duyên Prodhomme ◽

Josep Valls Fonayet ◽

Cyril Hévin ◽

Céline Franc ◽

Ghislaine Hilbert ◽

...

Keyword(s):

Amino Acids ◽

Secondary Metabolism ◽

Fruits And Vegetables ◽

Cell Formation ◽

Union Formation ◽

Primary Metabolism ◽

Graft Union ◽

Primary And Secondary Metabolites ◽

Primary And Secondary Metabolism ◽

Graft Interface

Abstract Background Grafting with rootstocks is essential for the culture of many perennial fruit crops and is increasing being used in the production of annual fruits and vegetables. Our previous work based on microarrays showed that transcripts encoding enzymes of both primary and secondary metabolism were differentially expressed during graft union formation in both homo-grafts (a genotype grafted with itself) and hetero-grafts (two different genotypes grafted together). The aim of this study was to profile primary and secondary metabolites, and quantify the activity of phenylalanine ammonia lyase (PAL) and neutral invertase (NI) in the scion and rootstock tissues and the graft interface of homo and hetero-grafts of grapevine 1 month after grafting. Table-top grafting was done on over-wintering stems (canes) of grapevine and the graft interface tissues (containing some woody stem tissues and callus) were compared to the surrounding rootstock and scion tissues. The objective was to identify compounds involved in graft union formation and hetero-grafting responses. Results A total of 54 compounds from primary and secondary metabolism (19 amino acids, five primary and 30 secondary compounds metabolites) and the activity of two enzymes were measured. The graft interface was associated with an increase in the accumulation of the branched-chain amino acids, basic amino acids, certain stilbene compounds and higher PAL and NI activity in comparison to the surrounding woody stem tissues. Some amino acids and stilbenes were identified as being accumulated differently between the graft interfaces of the scion/rootstock combinations in a manner which was unrelated to their concentrations in the surrounding woody stem tissues. Conclusions This study revealed the modification of primary metabolism to support callus cell formation and the stimulation of stilbene synthesis at the graft interface, and how these processes are modified by hetero-grafting. Knowledge of the metabolites and/or enzymes required for successful graft union formation offer us the potential to identify markers that could be used by nurseries and researchers for selection and breeding purposes.

Download Full-text

Subfunctionalization of Duplicate mitf Genes Associated With Differential Degeneration of Alternative Exons in Fish

Genetics ◽

10.1093/genetics/161.1.259 ◽

2002 ◽

Vol 161 (1) ◽

pp. 259-267 ◽

Cited By ~ 2

Author(s):

Joachim Altschmied ◽

Jacqueline Delfgaauw ◽

Brigitta Wilde ◽

Jutta Duschl ◽

Laurence Bouneau ◽

...

Keyword(s):

Danio Rerio ◽

Evolutionary History ◽

Single Gene ◽

Regulatory Elements ◽

Fugu Rubripes ◽

Gene Encoding ◽

Tetraodon Nigroviridis ◽

Mammalian Lineage ◽

History Of ◽

Fish Proteins

Abstract The microphthalmia-associated transcription factor (MITF) exists in at least four isoforms. These are generated in higher vertebrates using alternative 5′ exons and promoters from a single gene. Two separate genes (mitf-m and mitf-b), however, are present in different teleost fish species including the poeciliid Xiphophorus, the pufferfishes Fugu rubripes and Tetraodon nigroviridis, and the zebrafish Danio rerio. Fish proteins MITF-m and MITF-b correspond at both the structural and the expression levels to one particular bird/mammalian MITF isoform. In the teleost lineage subfunctionalization of mitf genes after duplication at least 100 million years ago is associated with the degeneration of alternative exons and, probably, regulatory elements and promoters. For example, a remnant of the first exon specific for MITF-m is detected within the pufferfish gene encoding MITF-b. Retracing the evolutionary history of mitf genes in vertebrates uncovered the differential recruitment of new introns specific for either the teleost or the bird/mammalian lineage.

Download Full-text

Structural diseases of the heart: syndromes affecting the cardiovascular system

ESC CardioMed ◽

10.1093/med/9780198784906.003.0162 ◽

2018 ◽

pp. 719-722

Author(s):

Sabine Klaassen

Keyword(s):

Single Gene ◽

Significant Proportion ◽

Signal Transduction Pathway ◽

Alagille Syndrome ◽

Mitogen Activated Protein Kinase ◽

Neurological Deficits ◽

Deletion Syndrome ◽

Gene Encoding ◽

Mitogen Activated Protein ◽

Craniofacial Features

Congenital heart disease (CHD) occurs in association with extracardiac anomalies or as part of an identified syndrome in 25–40% of cases. Approximately 30% of children with a chromosomal abnormality have CHD. Aneuploidy, or abnormal chromosomal number, accounts for a significant proportion of CHD. Of individuals born with trisomy 21, 50% have CHD, the most common being an atrioventricular septal defect (45%). In segmental aneuploidies, the so-called microdeletion syndromes, small submicroscopic chromosomal deletions can lead to CHD. The 22q11 deletion syndrome causes CHD with thymic and parathyroid hypoplasia (DiGeorge syndrome) and characteristic dysmorphic craniofacial features due to abnormal pharyngeal arch development. Williams–Beuren syndrome with renovascular anomalies, typical elfin facies, and neurological deficits, is characterized by cardiac involvement in the form of supravalvar aortic and peripheral pulmonic stenosis. Chromosome 1p36 deletion syndrome is the most common subterminal deletion syndrome. A substantial proportion of individuals with 1p36 deletion syndrome have CHD which may occur in the presence or absence of cardiomyopathy, most commonly left ventricular non-compaction cardiomyopathy. Single gene mutations may also cause syndromic CHD. Noonan syndrome and related disorders (‘RASopathies’) are caused by dominant gain-of-function mutations in one of the genes which encode proteins that function in the Ras/mitogen-activated protein kinase (RAS-MAPK) signal transduction pathway. Holt–Oram syndrome is associated with mutations in the transcription factor TBX5. Alagille syndrome is caused by mutations in JAG1, a gene encoding a ligand in the Notch signaling pathway. Heterotaxy syndrome, which means randomization of cardiac, pulmonary, or gastrointestinal situs, is frequently associated with CHD.

Download Full-text

In Silico Analysis of the CST6 Tumor Suppressor Gene

International Journal of Systems Biology and Biomedical Technologies ◽

10.4018/ijsbbt.2013070103 ◽

2013 ◽

Vol 2 (3) ◽

pp. 42-58

Author(s):

Athanasia Pavlopoulou ◽

Georgios Tsaramirsis

Keyword(s):

Tumor Suppressor ◽

Splice Variants ◽

Cpg Island ◽

Mammalian Species ◽

Gene Promoter ◽

In Silico Analysis ◽

Regulatory Elements ◽

Suppressor Gene ◽

Differentially Expressed ◽

Gene Encoding

The gene encoding cystatin E/M, CST6, is a Class II tumor suppressor. Using bioinformatics tools for database mining and virtual gene expression profiling, the authors showed that CST6 is differentially expressed in various types of cancer. Moreover, epigenetic silencing mediated by hypermethylation of the CpG island located at the CST6 promoter was found to be conserved in mammalian species. Comprehensive analyses of animal genomes led to the identification of novel CST6 transcript orthologs and splice variants that enabled us to trace the evolutionary origin of CST6. Moreover, eight novel and potentially regulatory SNPs were identified in CST6 gene. Conserved cancer-relevant regulatory elements were identified in the CST6 gene promoter. In addition, miRNAs that are differentially expressed in human cancers were identified as putative posttranscriptional regulators of CST6. Collectively, the authors suggest that expression of CST6 in normal and cancer cells is coordinately regulated by genomic, transcriptional and post-transcriptional mechanisms.

Download Full-text

The (p)ppGpp-mediated stringent response regulatory system globally inhibits primary metabolism and activates secondary metabolism in Pseudomonas protegens H78

Applied Microbiology and Biotechnology ◽

10.1007/s00253-020-10421-5 ◽

2020 ◽

Vol 104 (7) ◽

pp. 3061-3079 ◽

Cited By ~ 1

Author(s):

Lingyu Wu ◽

Zheng Wang ◽

Yejun Guan ◽

Xianqing Huang ◽

Huimin Shi ◽

...

Keyword(s):

Secondary Metabolism ◽

Regulatory System ◽

Stringent Response ◽

Primary Metabolism

Download Full-text

Mls is not a single gene, allelic system. Different stimulatory Mls determinants are the products of at least two nonallelic, unlinked genes.

Journal of Experimental Medicine ◽

10.1084/jem.166.4.1150 ◽

1987 ◽

Vol 166 (4) ◽

pp. 1150-1155 ◽

Cited By ~ 27

Author(s):

R Abe ◽

J J Ryan ◽

R J Hodes

Keyword(s):

T Cells ◽

Single Gene ◽

Surface Structures ◽

Chromosome 1 ◽

Gene Products ◽

Spleen Cells ◽

Gene Encoding ◽

Cell Surface Structures ◽

Genes Encoding ◽

Polymorphic Cell

Mls determinants share with MHC products the unique property of stimulating T cells at extraordinarily high precursor frequencies. The Mls system was originally described as a single locus on chromosome 1, with four alleles, Mlsa, Mlsb, Mlsc, and Mlsd, that encode polymorphic cell surface structures. However, the fundamental issues of polymorphism and allelism in the Mls system remain controversial. To clarify these questions, a formal segregation analysis of the genes encoding Mlsa and Mlsc determinants was carried out by testing the capacity of spleen cells from progeny of (Mlsa X Mlsc)F1 X Mlsb breedings to stimulate responses by unprimed T cells and by Mlsa- and Mlsc-specific cloned T cells. The results of this analysis indicated that the gene encoding Mlsa determinants is neither allelic to nor linked to the gene encoding Mlsc determinants. Together with previous findings, these results also suggest that another strongly stimulatory type, Mlsd, in fact results from the independent expression of unlinked Mlsa and Mlsc gene products. Based on these observations, it is concluded that, contrary to conventional concepts, the stimulatory phenotypes designated as Mlsa, Mlsc, and Mlsd can be accounted for by the independent expression of the products of at least two unlinked gene loci.

Download Full-text