Subcellular localization of fungal specialized metabolites

Skellam, Elizabeth

doi:10.1186/s40694-022-00140-z

Cited by 10 publications

(9 citation statements)

References 138 publications

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“…To modify host strains to improve target compound production, it is reasonable to optimize the localization of the corresponding biosynthetic enzymes in the cells. Some of the fungal peptidyl compounds reviewed by Skellam (2022) are synthesized in compartments. For example, IAT responsible for penicillin biosynthesis, localizes in peroxisomes ( Meijer et al., 2010 ), and SimA functioning as cyclosporin synthetase, localizes in vacuoles ( Hoppert et al., 2001 ).…”

Section: Discussionmentioning

confidence: 99%

How to improve the production of peptidyl compounds in filamentous fungi

Umemura¹,

Tamano²

2022

Front. Fungal Biol.

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Peptidyl compounds produced by filamentous fungi, which are nonribosomal peptides (NRPs) and ribosomally synthesized and post-translationally modified peptides (RiPPs), are rich sources of bioactive compounds with a wide variety of structures. Some of these peptidyl compounds are useful as pharmaceuticals and pesticides. However, for industrial use, their low production often becomes an obstacle, and various approaches have been challenged to overcome this weakness. In this article, we summarize the successful attempts to increase the production of NRPs and RiPPs in filamentous fungi and present our perspectives on how to improve it further.

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Section: Discussionmentioning

confidence: 99%

How to improve the production of peptidyl compounds in filamentous fungi

Umemura¹,

Tamano²

2022

Front. Fungal Biol.

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“…Relatively few reports have focused on the subcellular compartmentalization of biosynthesis steps. Enzymes required for the biosynthesis of fungal SMs may reside in the cytosol, peroxisome, and other delimited membrane-bound organelles, like vacuoles, vesicles, endosomes, and toxisomes (Skellam, 2022). The complexity of fungal secondary metabolism may therefore also stem from the individuality of the producing hyphae, but so far it is unclear whether such differential spatial expression of biosynthetic enzyme-encoding genes is the norm or the exception.…”

Section: Compa Rtm Ent Ali Z Ation Of P Olyke Tide B Iosynthe S Is In...mentioning

confidence: 99%

Complexity of fungal polyketide biosynthesis and function

Stroe,

Gao,

Pitz

et al. 2023

Molecular Microbiology

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Where does one draw the line between primary and secondary metabolism? The answer depends on the perspective. Microbial secondary metabolites (SMs) were at first believed not to be very important for the producers because they are dispensable for growth under laboratory conditions. However, such compounds become important in natural niches of the organisms, and some are of prime importance for humanity. Polyketides are an important group of SMs with aflatoxin as a well‐known and well‐characterized example. In Aspergillus spp., all 34 afl genes encoding the enzymes for aflatoxin biosynthesis are located in close vicinity on chromosome III in a so‐called gene cluster. This led to the assumption that most genes required for polyketide biosynthesis are organized in gene clusters. Recent research, however, revealed an enormous complexity of the biosynthesis of different polyketides, ranging from individual polyketide synthases to a gene cluster producing several compounds, or to several clusters with additional genes scattered in the genome for the production of one compound. Research of the last decade furthermore revealed a huge potential for SM biosynthesis hidden in fungal genomes, and methods were developed to wake up such sleeping genes. The analysis of organismic interactions starts to reveal some of the ecological functions of polyketides for the producing fungi.

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“…An increasing number of different subcellular localizations of enzymes involved in the biosynthesis of fungal metabolites have been described recently [ 17 ]. For example, in P. chrysogenum and Aspergillus nidulans , the first two enzymes of the penicillin pathway are located in the cytosol, whereas the late enzymes involved in the formation of aromatic penicillins (benzylpenicillin and phenoxymethylpenicillin) are located in peroxisomes [ 16 ].…”

Section: Numerous Transporters Are Involved In the Translocation Of F...mentioning

confidence: 99%

“…For example, in P. chrysogenum and Aspergillus nidulans , the first two enzymes of the penicillin pathway are located in the cytosol, whereas the late enzymes involved in the formation of aromatic penicillins (benzylpenicillin and phenoxymethylpenicillin) are located in peroxisomes [ 16 ]. Subcellular localization of the secondary metabolites biosynthetic enzymes is a very dynamic process and requires targeting the adequate cellular localization [ 17 ].…”

Section: Numerous Transporters Are Involved In the Translocation Of F...mentioning

confidence: 99%

“…In the last decade, evidence has been provided that biosynthesis and secretion of secondary metabolites is an elaborate process that proceeds through several organelles and vesicles (e.g., multivesicular microbodies) [ 17 , 97 ]. Some transporters described in microbodies may be located in peroxisome-related multivesicular structures [ 39 ], although the role of these vesicular structures in the secretion of fungal metabolites is unclear [ 16 , 98 ].…”

Section: Conclusion and Future Outlookmentioning

confidence: 99%

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Vacuolal and Peroxisomal Calcium Ion Transporters in Yeasts and Fungi: Key Role in the Translocation of Intermediates in the Biosynthesis of Fungal Metabolites

Martı́n

2022

Genes

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The intracellular calcium content in fungal cells is influenced by a large number of environmental and nutritional factors. Sharp changes in the cytosolic calcium level act as signals that are decoded by the cell gene expression machinery, resulting in several physiological responses, including differentiation and secondary metabolites biosynthesis. Expression of the three penicillin biosynthetic genes is regulated by calcium ions, but there is still little information on the role of this ion in the translocation of penicillin intermediates between different subcellular compartments. Using advanced information on the transport of calcium in organelles in yeast as a model, this article reviews the recent progress on the transport of calcium in vacuoles and peroxisomes and its relation to the translocation of biosynthetic intermediates in filamentous fungi. The Penicillium chrysogenum PenV vacuole transporter and the Acremonium chrysogenum CefP peroxisomal transporter belong to the transient receptor potential (TRP) class CSC of calcium ion channels. The PenV transporter plays an important role in providing precursors for the biosynthesis of the tripeptide δ-(-α-aminoadipyl-L-cysteinyl-D-valine), the first intermediate of penicillin biosynthesis in P. chrysogenum. Similarly, CefP exerts a key function in the conversion of isopenicillin N to penicillin N in peroxisomes of A. chrysogenum. These TRP transporters are different from other TRP ion channels of Giberella zeae that belong to the Yvc1 class of yeast TRPs. Recent advances in filamentous fungi indicate that the cytosolic calcium concentration signal is connected to the calcitonin/calcineurin signal transduction cascade that controls the expression of genes involved in the subcellular translocation of intermediates during fungal metabolite biosynthesis. These advances open new possibilities to enhance the expression of important biosynthetic genes in fungi.

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Subcellular localization of fungal specialized metabolites

Cited by 10 publications

References 138 publications

How to improve the production of peptidyl compounds in filamentous fungi

How to improve the production of peptidyl compounds in filamentous fungi

Complexity of fungal polyketide biosynthesis and function

Vacuolal and Peroxisomal Calcium Ion Transporters in Yeasts and Fungi: Key Role in the Translocation of Intermediates in the Biosynthesis of Fungal Metabolites

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