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Filamentous fungi produce a vast number of bioactive secondary metabolites (SMs), some of which have found applications in the pharmaceutical industry including as antibiotics and immunosuppressants. As more and more species are whole genome sequenced the number of predicted clusters of genes for SM biosynthesus is ever increasing - holding a promise of novel useful bioactive SMs. To be able to fully utilize the potential of novel SMs, it is necessary to link the SM and the genes responsible for producing it. This can be challenging, but many strategies and tools have been developed for this purpose. Here we provide an overview of the methods used to establish the link between SM and biosynthetic gene cluster (BGC) and vice versa, along with the challenges and advantages of each of the methods. Part I of the review, associating BCG with SM, is divided into gene manipulations native strain and heterologous expression strategies, depending on the fungal species. Part II, associating SM with BGC, is divided into three main approaches: 1) homology search 2) retro-biosynthesis and 3) comparative genomics.
This article was published in the following journal.
Name: Fungal genetics and biology : FG & B
Bacteria and fungi are prolific producers of secondary metabolites, yet they house a multitude of silent biosynthetic gene clusters that are poorly expressed and whose products are unknown or 'cryptic...
Filamentous cyanobacteria belong to the most prolific producers of structurally unique and biologically active natural products, yet the majority of biosynthetic gene clusters predicted for these mult...
Fungi produce an abundance of bioactive secondary metabolites which can be utilized as antibiotics and pharmaceutical drugs. The genes encoding secondary metabolites are contiguously arranged in biosy...
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An enzyme that catalyzes the cyclization of hydroxymethylbilane to yield UROPORPHYRINOGEN III and water. It is the fourth enzyme in the 8-enzyme biosynthetic pathway of HEME, and is encoded by UROS gene. Mutations of UROS gene result in CONGENITAL ERYTHROPOIETIC PORPHYRIA.
An enzyme that catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX by the conversion of two propionate groups to two vinyl groups. It is the sixth enzyme in the 8-enzyme biosynthetic pathway of HEME, and is encoded by CPO gene. Mutations of CPO gene result in HEREDITARY COPROPORPHYRIA.
An enzyme that catalyzes the formation of anthranilate (o-aminobenzoate) and pyruvic acid from chorismate and glutamine. Anthranilate is the biosynthetic precursor of tryptophan and numerous secondary metabolites, including inducible plant defense compounds. EC 188.8.131.52.
A multi-functional catenin that is highly homologous to BETA CATENIN. Gamma catenin binds CADHERINS and helps link their cytoplasmic tails to ACTIN in the CYTOSKELETON via ALPHA CATENIN. It is also found in DESMOSOMES where it mediates the link between DESMOSOMAL CADHERINS and DESMOPLAKIN.
A secondary structure of proteins where the amino (N-H) groups of a polypeptide backbone, three to ten amino acids in length, establish hydrogen bonds with the carbonyl (C=O) groups in the backbone of adjacent strands. These may form a beta-sheet, where the side chains of the adjacent strands point in the same direction.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...