Category Archives: secondary metabolite

Some recent fungal and oomycete genome papers A few papers covering some published genomes you should definitely read if you have the chance.

  • Youssef NH, Couger MB, Struchtemeyer CG, Liggenstoffer AS, Prade RA, Najar FZ, Atiyeh HK, Wilkins MR, & Elshahed MS (2013). The Genome of the Anaerobic Fungus Orpinomyces sp. Strain C1A Reveals the Unique Evolutionary History of a Remarkable Plant Biomass Degrader. Applied and environmental microbiology, 79 (15), 4620-34 PMID: 23709508
    Describes first published genome of a Neocallimastigomycota fungus that resides within the rumen gut. Cool findings related to lignocellulolytic degradation pathways and basic biology about early diverging fungi which have intact flagellar apparatus.
  • Bushley KE, Raja R, Jaiswal P, Cumbie JS, Nonogaki M, Boyd AE, Owensby CA, Knaus BJ, Elser J, Miller D, Di Y, McPhail KL, & Spatafora JW (2013). The Genome of Tolypocladium inflatum: Evolution, Organization, and Expression of the Cyclosporin Biosynthetic Gene Cluster. PLoS Genetics, 9 (6) PMID: 23818858Describes the genome of a pathogen of beetle larvae (and related to Cordyceps). This fungus is important as it produces the immunosuppresive drug cyclosporin as a secondary metabolite. Analysis of the complete secondary metabolite pathways in the genome help shed light on the origin of this and other secondary metabolite gene clusters.
  • Schardl CL, Young CA, Hesse U, Amyotte SG, Andreeva K, Calie PJ, Fleetwood DJ, Haws DC, Moore N, Oeser B, Panaccione DG, Schweri KK, Voisey CR, Farman ML, Jaromczyk JW, Roe BA, O’Sullivan DM, Scott B, Tudzynski P, An Z, Arnaoudova EG, Bullock CT, Charlton ND, Chen L, Cox M, Dinkins RD, Florea S, Glenn AE, Gordon A, Güldener U, Harris DR, Hollin W, Jaromczyk J, Johnson RD, Khan AK, Leistner E, Leuchtmann A, Li C, Liu J, Liu J, Liu M, Mace W, Machado C, Nagabhyru P, Pan J, Schmid J, Sugawara K, Steiner U, Takach JE, Tanaka E, Webb JS, Wilson EV, Wiseman JL, Yoshida R, & Zeng Z (2013). Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the clavicipitaceae reveals dynamics of alkaloid loci. PLoS Genetics, 9 (2) PMID: 23468653 

    A very rich and detailed paper, this presents a gold mine of complete genome data of 15 species and secondary metabolite profiling. The data include genomes of 10 epichloae fungi that are endophytes of grasses, three Claviceps species (ergot fungi), a morning-glory symbiont and a bamboo pathogen. The analyses of the genes from pathway analyses of the genomes along with profiling alkaloid productions the authors were able to link clusters to products in many cases. This is a rich and useful paper for anyone working in this field of secondary metabolites and sets the standard for a how a biological question can be answered by genome sequencing of a clade of related species.

  • Wicker T, Oberhaensli S, Parlange F, Buchmann JP, Shatalina M, Roffler S, Ben-David R, Doležel J, Simková H, Schulze-Lefert P, Spanu PD, Bruggmann R, Amselem J, Quesneville H, van Themaat EV, Paape T, Shimizu KK, & Keller B (2013). The wheat powdery mildew genome shows the unique evolution of an obligate biotroph. Nature Genetics PMID: 23852167

    Genome of wheat pathogen Blumeria graminis f.sp. tritici.This paper includes an identification and analysis of effector genes and dating the emergence of the pathogen relative the domestication and diversification of wheat.
  • Jiang RH, de Bruijn I, Haas BJ, Belmonte R, Löbach L, Christie J, van den Ackerveken G, Bottin A, Bulone V, Díaz-Moreno SM, Dumas B, Fan L, Gaulin E, Govers F, Grenville-Briggs LJ, Horner NR, Levin JZ, Mammella M, Meijer HJ, Morris P, Nusbaum C, Oome S, Phillips AJ, van Rooyen D, Rzeszutek E, Saraiva M, Secombes CJ, Seidl MF, Snel B, Stassen JH, Sykes S, Tripathy S, van den Berg H, Vega-Arreguin JC, Wawra S, Young SK, Zeng Q, Dieguez-Uribeondo J, Russ C, Tyler BM, & van West P (2013). Distinctive Expansion of Potential Virulence Genes in the Genome of the Oomycete Fish Pathogen Saprolegnia parasitica. PLoS Genetics, 9 (6) PMID: 23785293

    Genome of the fish pathogen and Oomycete Saprolegnia provide additional perspective on this diverse group organisms, evolution of metabolism and host-associated lifestyles.
  • Aylward FO, Burnum-Johnson KE, Tringe SG, Teiling C, Tremmel DM, Moeller JA, Scott JJ, Barry KW, Piehowski PD, Nicora CD, Malfatti SA, Monroe ME, Purvine SO, Goodwin LA, Smith RD, Weinstock GM, Gerardo NM, Suen G, Lipton MS, & Currie CR (2013). Leucoagaricus gongylophorus produces diverse enzymes for the degradation of recalcitrant plant polymers in leaf-cutter ant fungus gardens. Applied and environmental microbiology, 79 (12), 3770-8 PMID: 23584789Genome of the ant farmed fungus Leucoagaricus. This paper presents a draft genome assembly a useful step in understanding the fascinating symbiosis between ants and their cultivated fungi.

Horizontal gene transfer from Zygo to pea aphid

Pea AphidAnother result from the analysis of the recently published genome of the pea aphid, Acyrthosiphon pisum. Nancy Moran and Tyler Jarvik present a study of the origin of the carotenoid production gene in pea aphid. Animals typically cannot make carotenoids so they sought to discover how this is possible. They find that it is derived from a horizontal gene transfer event of a fungal gene into the aphid lineage. This gene is responsible for the red-green color polymorphism in the aphid. It appears the gene is derived from a ‘zygomycete’ or relative in the early branching lineage of the fungi. One gene, a carotenoid desaturase, is encoded in a 30kb genomic region that is missing in green aphids but present in the red morphs. The region is apparently maintained in the population by frequency dependent selection since each color has an advantage or disadvantage for evading detection by predators in different environments.

The reports of eukaryotic HGT event from fungi to animals is quite rare so this finding is surprising in that sense, but the authors argue that the important ecological role of carotenoids suggest we might see even more examples if we look harder.

Moran, N., & Jarvik, T. (2010). Lateral Transfer of Genes from Fungi Underlies Carotenoid Production in Aphids Science, 328 (5978), 624-627 DOI: 10.1126/science.1187113

Genome survey sequencing of Witches’ Broom

Genome survey sequencing (1.9X coverage) was generated for Moniliophthora perniciosa, the cause of witches’ broom disease on cacao plants. The sequence for this basidiomycete plant pathogen was published in BMC Genomics this week. The authors report a higher number of ROS metabolism and P450 genes. Evaluating whether these copy number differences are significantly different from other basidiomycete fungi and are lineage specific expansions will help determine if these families played a role in the adaptation of this plant pathogen.

This work provides an important stepping stone in understanding and eventually controlling this pathogen which is devastating cacao plantations. An associated review describes what we have and can learn about Witches’ broom disease.

See related:

Jorge MC Mondego, Marcelo F Carazzolle, Gustavo GL Costa, Eduardo F Formighieri, Lucas P Parizzi, Johana Rincones, Carolina Cotomacci, Dirce M Carraro, Anderson F Cunha, Helaine Carrer, Ramon O Vidal, Raissa C Estrela, Odalys Garcia, Daniela PT Thomazella, Bruno V de Oliveira, Acassia BL Pires, Maria Carolina S Rio, Marcos Renato R Araujo, Marcos H de Moraes, Luis AB Castro, Karina P Gramacho, Marilda S Goncalves, Jose P Moura Neto, Aristoteles Goes Neto, Luciana V Barbosa, Mark J Guiltinan, Bryan A Bailey, Lyndel W Meinhardt, Julio CM Cascardo, Goncalo AG Pereira (2008). A genome survey of Moniliophthora perniciosa gives new insights into Witches’ Broom Disease of cacao BMC Genomics, 9 (1) DOI: 10.1186/1471-2164-9-548

Fungal P450s

A paper (Park et al, BMC Genomics) from Fungal Bioinformatics Lab at Seoul University in South Korea describes their new “Fungal P450 Database”. The database contains sequence, names, and genome links for P450’s (or Cytochrome P450s) identified by similarity and phylogenetic classification from genome annotations.  The group is using most of annotated genomes in GenBank (and I think some from elsewhere) of bacterial, fungi, animals, and plants.

I find the current nomenclature for this family of genes confusing but it has been I am sure a difficult job and wrangled to a large part by David Nelson (who also has a new paper on the CYPome of Aspergillus nidulans). I have found it difficult to follow the logic for naming these members, as it didn’t seem to be particularly phylogenetic at first, although I think that has improved. However, a stable and solid reference database is needed to for naming these gene members and for mapping new members in through straightforward analyses is an essential resource. Park et al have made great inroads to that end and it may indeed meet needs (I am cautious to say it is solved without more exploration or some sense of whether it is intended or will be taken up as just that sort of reference by the P450 community).  It has seemed to me that a proper phylogenetic (or really, a phylogenomic) approach is essential for naming the P450 member genes as orthologous or paralogous members across multiple species. The group has defined their classes as clusters of homologs (e.g. Mg004 is Magnaporthe grisea gene in Cluster 9.1) and linked these also to the Nelson nomeclature (CYP68E1).  By defining orthologous family members we can make more interpretations about how to transfer functional annotation in a truly phylogenomic context. 

The overall family is so large and diverse (they report 4538 fungal P450s into 141 clusters/sub-families from 68 species) across many different species. The fungi tend to have very large families in some clades (e.g. some filamentous fungi) so I think this type of systematic and searchable system that will have stable identities for clusters is an essential resource. I know I’m going to try and give it a whirl. We have a couple of cool findings about changes in the P450 families in Basidiomycete Coprinopsis and related species comparisons that I hope we’ll be able to better interpret with this additional phylogenomic naming of gene family members.

Jongsun Park, Seungmin Lee, Jaeyoung Choi, Kyohun Ahn, Bongsoo Park, Jaejin Park, Seogchan Kang, Yong-Hwan Lee (2008). Fungal cytochrome P450 database BMC Genomics, 9 (1) DOI: 10.1186/1471-2164-9-402

Deconstructing aflatoxin biosynthesis

A paper in Science from Jason Crawford and colleagues explores the function of polyketide synthetases (PKS) in the synthesis of the secondary metabolite and carcinogen aflatoxin. Previous work (nicely reviewed in the fungi by Nancy Keller and colleagues) has shown the the PKS genes have several domains. These domains include acyl carrier protein (ACP), transacylase (SAT), ketosynthase (KS), malonyl-CoA:ACP transacylase (MAT), “product template” PT, Aand thioesterase/Claisen cyclase (TE/CLC).  These domains make up PksA, but the specific role of each domain’s in synthesis steps has not been fully worked out. Understanding this process and the specificity of the chemical structures that are created can help in redesign of these enzymes for synthesis of new molecules and drugs.

Then authors cloning and combining the domains from a cDNA template of pksA [accession AY371490]  (from Aspergillus parasiticus) into various combinations and then evaluated the synthesized products via HPLC.  This deconstruction of a complicated protein and its domains is a great example of functionally mapping the role of each part of the enzyme and integrating with the biochemistry of the synthesized products.  The findings of this research also mapped a role for the PT product template domain which could suggest where modifications could be made to tweak the synthesized products by these enzymes.

Crawford, J.M., Thomas, P.M., Scheerer, J.R., Vagstad, A.L., Kelleher, N.L., Townsend, C.A. (2008). Deconstruction of Iterative Multidomain Polyketide Synthase Function. Science, 320(5873), 243-246. DOI: 10.1126/science.1154711

Phytopathogenic Fungi: what have we learned from genome sequences?

ResearchBlogging.orgA review in Plant Cell from Darren Soanes and colleagues summarizes some of the major findings about evolution of phytopathogenic fungi gleaned from genome sequencing highlighting 12 fungi and 2 oomycetes. By mapping evolution of genes identified as virulence factors as well as genes that appear to have similar patterns of diversification, we can hope to derive some principals about how phytopathogenic fungi have evolved from saprophyte ancestors.

They infer from phylogenies we’ve published (Fitzpatrick et al, James et al) that plant pathogenic capabilities have arisen at least 5 times in the fungi and at least 7 times in the eukaryotes. In addition they use data on gene duplication and loss in the ascomycete fungi (Wapinski et al) to infer there large numbers of losses and gains of genes have occurred in fungal lineages.

Continue reading Phytopathogenic Fungi: what have we learned from genome sequences?

Amanita toxin genes

A. bisporigeraMichigan State researchers Heather Hallen and Jonathan Walton have reportedly cloned genes from Amanita for alpha-amanitin (mispelled as alpha-aminitin in NYTimes article) which inhibits RNA polymerase II and phallacidin which inhibits actin filament polymerization. The gene sequences are in GenBank for those itching to look at evolutionary relationships of these genes in other fungi.

This is unfortunately another annoying example of science-by-press release where the PNAS publication is not available but the press release and NYtimes article are, but that shouldn’t take aware from a cool result. We also had to wait a week after the dandruff genome announcement to read that paper, I hope the PNAS press-release publication-release timeline gets synchronized soon…

Update: Gene family encoding the major toxins of lethal Amanita mushrooms manuscript is available now.

A writeup about the A. bisporigera “destroying angel” shown here can be read at the Cornell Mushroom blog and the deadly consequences of ingesting it.

[Thanks ShannonS via FredS]

Evolution of aflatoxin gene cluster

Blogging on Peer-Reviewed ResearchIgnazio Carbone and colleagues published a recent analysis of the evolution of the aflatoxin gene cluster in five Aspergillus fungi entitled “Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster” in BMC Evolutionary Biology. The authors were able to identify seven modules pairs of genes whose history of duplication were highly correlated. Several genomes of Aspergillus have been sequenced along with more Eurotioales fungi. Continue reading Evolution of aflatoxin gene cluster

Genomes on the horizon at JGI

Several more fungi are on the docket for sequencing at JGI through their community sequencing program. This includes

This complements an ever growing list of fungal genome sequences which is probably topping 80+ now not including the several dozen strains of Saccharomyces that are being sequenced at Sanger Centre and a separately funded NIH project to be sequenced at WashU.

Exploring a global regulator of gene expression in Aspergillus

Blogging about Peer-Reviewed ResearchWhen first discovered, the gene LaeA was thought to be a master switch for silencing of several NRPS secondary metabolite gene clusters in Aspergillus. NRPS and PKS are important genes in filamentous fungi as they produce many compounds that likely help fungi compete in the ecological niche mycotoxins (e.g. aflatoxin, gliotoxin), plant hormone (e.g. Gibberellin), and a potential wealth of additional undiscovered activities.

A recent paper from Nancy Keller’s lab entitled Transcriptional Regulation of Chemical Diversity in Aspergillus fumigatus by LaeA has followed up previous studies with whole genome expression profiling of a LaeA knockout strain to explore the breadth of the genome that is regulated by this transcriptional regulator. Continue reading Exploring a global regulator of gene expression in Aspergillus