Mind the mushroom: natural product biosynthetic genes and enzymes of Basidiomycota

Gressler, Markus; Löhr, Nikolai A; Schäfer, Tim; Lawrinowitz, Stefanie; Seibold, Paula Sophie; Hoffmeister, Dirk

doi:10.1039/d0np00077a

Cited by 78 publications

(78 citation statements)

References 211 publications

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“…Based on recent genome surveys it appears that the fungal secondary metabolome is extremely diverse and is a largely untapped resource of natural products and bioactive molecules (Keller 2019). This may be particularly true for the Agaricomycetes, despite several lines of evidence for a large diversity of secondary metabolites produced by Agaricomycetes (Spiteller 2015;Gressler et al 2021). From the perspective of fruiting body formation, it is important to note that secondary metabolites can serve defense or repellent purposes in fruiting bodies (see chapter on Defense) but can also influence developmental processes.…”

Section: Secondary Metabolism and Natural Product Biosynthesismentioning

confidence: 99%

“…Secondary metabolites are one of the most important classes of molecules in chemical warfare and developmental signaling in fungi (Spiteller 2015;Keller 2019;Gressler et al 2021). Based on recent genome surveys it appears that the fungal secondary metabolome is extremely diverse and is a largely untapped resource of natural products and bioactive molecules (Keller 2019).…”

Section: Secondary Metabolism and Natural Product Biosynthesismentioning

confidence: 99%

“…The number of functionally characterized secondary metabolism genes and linked natural products of Agaricomycetes is rapidly increasing. For example, ArmB and orsellinic acid in Armillaria spp (Lackner et al 2013), LpaA and laetiporic acid in Laetiporus sp (Seibold et al 2020), or St.pks1 and strobilurin in Strobilurus tenacellus (Nofiani et al 2018) as well as numerous terpene synthases have been circumscribed in the past decade (reviewed in more detail by (Gressler et al 2021)). Strobilurin derivatives are available commercially and are the world's most sold fungicides (DW et al 2002).…”

Section: Secondary Metabolism and Natural Product Biosynthesismentioning

confidence: 99%

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Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes

Nagy

Vonk

Künzler

et al. 2021

Preprint

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Fruiting bodies of mushroom-forming fungi (Agaricomycetes) are among the most complex structures produced by fungi. Unlike vegetative hyphae, fruiting bodies grow determinately and follow a genetically encoded developmental program that orchestrates tissue differentiation, growth and sexual sporulation. In spite of more than a century of research, our understanding of the molecular details of fruiting body morphogenesis is limited and a general synthesis on the genetics of this complex process is lacking. In this paper, we aim to comprehensively identify conserved genes related to fruiting body morphogenesis and distill novel functional hypotheses for functionally poorly characterized genes. As a result of this analysis, we report 921 conserved developmentally expressed gene families, only a few dozens of which have previously been reported in fruiting body development. Based on literature data, conserved expression patterns and functional annotations, we provide informed hypotheses on the potential role of these gene families in fruiting body development, yielding the most complete description of molecular processes in fruiting body morphogenesis to date. We discuss genes related to the initiation of fruiting, differentiation, growth, cell surface and cell wall, defense, transcriptional regulation as well as signal transduction. Based on these data we derive a general model of fruiting body development, which includes an early, proliferative phase that is mostly concerned with laying out the mushroom body plan (via cell division and differentiation), and a second phase of growth via cell expansion as well as meiotic events and sporulation. Altogether, our discussions cover 1480 genes of Coprinopsis cinerea, and their orthologs in Agaricus bisporus, Cyclocybe aegerita, Armillaria ostoyae, Auriculariopsis ampla, Laccaria bicolor, Lentinula edodes, Lentinus tigrinus, Mycena kentingensis, Phanerochaete chrysosporium, Pleurotus ostreatus, and Schizophyllum commune, providing functional hypotheses for ~10% of genes in the genomes of these species. Although experimental evidence for the role of these genes will need to be established in the future, our data provide a roadmap for guiding functional analyses of fruiting related genes in the Agaricomycetes. We anticipate that the gene compendium presented here, combined with developments in functional genomics approaches will contribute to uncovering the genetic bases of one of the most spectacular multicellular developmental processes in fungi. Key words: functional annotation; comparative genomics; cell wall remodeling; development; fruiting body morphogenesis; mushroom; transcriptome

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Section: Secondary Metabolism and Natural Product Biosynthesismentioning

confidence: 99%

Section: Secondary Metabolism and Natural Product Biosynthesismentioning

confidence: 99%

Section: Secondary Metabolism and Natural Product Biosynthesismentioning

confidence: 99%

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Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes

Nagy

Vonk

Künzler

et al. 2021

Preprint

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“…To correlate detected volatiles to the biosynthetic capacity of Termitomyces , we analyzed the draft genomes of eight Termitomyces strains using the platform fungiSMASH (v6.0) and web service NRPSpredictor2 (see Table S73 at https://doi.org/10.6084/m9.figshare.16702471 ) ( 32 , 33 ). Overall, each fungal genome encoded more than 20 detectable biosynthetic features related to secondary metabolism, including predominately fungal terpene cyclases (TCs), one nonreducing iterative type I polyketide synthase (NR-PKS) with conserved domain architecture (SAT-KS-AT-PT-ACP-ACP-TE), and a nonribosomal peptide synthetase (NRPS) with a conserved domain architecture (A 1 -T 1 -C 1 -T 2 -C 2 -T 3 -C 3 ) and an adjacent putative cytochrome P450 monooxygenase ( 34 ). Phylogenetic analysis of the NR-PKS sequences revealed their close relationship to known orsellinic acid-producing synthases described from other basidiomycetes ( 35 , 36 ), while an analysis of the detected NRPS sequences indicated their close relationship to one of the most abundant type VI basidiomycete siderophore synthetases that is assumed to produce the trimeric siderophore basidioferrin, derived from N 5 -acylated N 5 -hydroxy -l -ornithine ( l -AHO) (see Table S73 and Fig.…”

Section: Resultsmentioning

confidence: 99%

Comparative Genomic and Metabolomic Analysis of Termitomyces Species Provides Insights into the Terpenome of the Fungal Cultivar and the Characteristic Odor of the Fungus Garden of Macrotermes natalensis Termites

et al. 2022

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The symbiosis between macrotermitinae termites and Termitomyces is obligate for both partners and is one of the most important contributors to biomass conversion in the Old World tropic’s ecosystems. To date, research efforts have dominantly focused on acquiring a better understanding of the degradative capabilities of Termitomyces to sustain the obligate nutritional symbiosis, but our knowledge of the small-molecule repertoire of the fungal cultivar mediating interspecies and interkingdom interactions has remained fragmented.

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“…Yet, most reports are related to products from Ascomycota or dealing with engineered yeasts as a heterologous producers. Reports about processes to obtain compounds from Basidiomycota are hard to nd and little information is available in literature about biotechnological development with those organisms speci cally for the production of pharmaceuticals (16)(17)(18). This publication outlines one approach for transferring the production of illudin M from a high yield shake ask process into a scalable process in stirred tank bioreactors.…”

Section: Introductionmentioning

confidence: 99%

Optimization of the production process for the anticancer lead compound illudin M II. Process development in stirred tank bioreactors

Chaverra-Muñoz

Hüttel

2022

Preprint

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Background: The fungal natural products illudin S and M have been investigated as precursors for the development of semisynthetic anticancer agents such as Irofulven (illudin S derivative) which is currently in phase II clinical trials. Recently, illudin M derivatives have shown in vitro improved selectivity towards cancer cells encouraging further investigations. This requires a stable supply of the precursor which is produced by Basidiomycota of the genus Omphalotus. We have recently developed a stable process for the production of gram quantities of illudin M from Omphalotus nidiformis in shake flasks, but transferring such findings into stirred tank bioreactors - which can be used in a commercial production set-up - is often not straightforward and is particularly challenging when the producer can undergo morphological changes. There are only few reports addressing bioprocess development for production of compounds from Basidiomycota since these organisms have been underexplored i.a because they have complex life cycles and many of them are difficult to cultivate under laboratory conditions.Results: The recently developed shake flask process yielding stable titers of ~940 mg L-1 of illudin M was evaluated using off-gas analysis, and critical parameters were identified to facilitate the transfer from shaken into stirred tank bioreactors. The process was adapted in 2 L stirred tank bioreactors (1.5 L working volume) by controlling growth of biomass with a carefully timed pH-shift combined with an improved precursor-feeding strategy. This resulted in comparable titers as in shake flasks. A scale-up experiment in a 15 L bioreactor (10 L working volume), resembling the process at 1.5 L resulted in illudin M >500 mg L-1 and will be the starting point for optimization of the identified parameters at that scale.Conclusion: By identifying and controlling key process parameters, the production process for illudin M was transferred from shake flasks into stirred tank bioreactors reaching comparable titers (> 900 mg L-1) which is significantly higher than any previously reported yield. The established bioprocess at bench-scale (~500 mg L-1) paves the way towards further scale-up studies that will enable industrial supply of illudin M to support preclinical and clinical development programs.

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Mind the mushroom: natural product biosynthetic genes and enzymes of Basidiomycota

Abstract: This article comprehensively reviews basidiomycete enzymes and their genes involved in natural product biosynthesis and primarily focuses on typical pathways and enzymes, along with the methods applied to investigate mushroom metabolism.

Cited by 78 publications

References 211 publications

Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes

Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes

Comparative Genomic and Metabolomic Analysis of Termitomyces Species Provides Insights into the Terpenome of the Fungal Cultivar and the Characteristic Odor of the Fungus Garden of Macrotermes natalensis Termites

Optimization of the production process for the anticancer lead compound illudin M II. Process development in stirred tank bioreactors

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