Return of the Fungi

Fungal Genomics

The genome sequence of Saccharomyces cerevisiae was published in 1996. ⁹ It was the first eukaryotic genome sequence published. Over the following several years, additional fungal genomes were sequenced and analyzed. ^{5,10 –17} Highlighted on the cover of this issue of IB is a helium ion micrograph of Yarrowia lipolytica, an oleaginous yeast that accumulates lipids and may be a promising source of biofuels and biofuel precursors. It represents one of the “early” fungal genomes to be sequenced. Over the years, as sequencing throughputs have increased and costs have decreased, what was once a trickle of fungal genomics data is now a roaring river of sequence data. The Department of Energy (DOE) Joint Genome Institute (JGI) led the sequencing and analysis of the first Basidiomycete genome, Phanerochate chrysosporium. ¹⁴ The JGI has played a critical role in keeping fungal genomics at the cutting edge and focused on research relevant to energy and environmental science.

The JGI has increased its productivity in fungal genomics every year and is now hosting the 1000 Fungal Genomes Project. In addition to providing reference genomes that will better enable large metagenomic studies in which fungi play important roles in environmental processes, this project will greatly augment the catalog of fungal enzymes and metabolic pathways that are useful in biofuel and renewable chemical applications. ^{18 –20} Industrial Biotechnology interviewed Igor Grigoriev, who leads the JGI Fungal Genomics Program. Dr. Grigoriev talks about the importance of the 1000 Fungal Genomes Project. In addition, he highlights the strong contributions the JGI has made to fungal genomics over the last several years. He explains how the JGI Fungal Genomics Program is helping to accelerate fungal research for DOE mission science in energy and the environment and highlights a number of collaborative projects with academic, government and industry laboratories.

Expanding the Molecular Genetic Toolbox

The number of fungi being studied continues to increase as new molecular genetic tools are developed. Molecular genetic toolsets for model organisms such as Neurospora crassa and Aspergillus nidulans are well established, and those for other organisms are also under continuous development and improvement. Over the last several years, a robust genetic toolset emerged for Trichoderma reesei, A. niger, and many other filamentous ascomycetes. ^{21 –24} In another IB interview with Randy Berka of Novozymes, he describes how genetic toolbox development has positively impacted the way in which fungi have been able to propel the biotechnology industry. ²⁵ At the beginning of his career the toolbox was limited to major genetic model organisms, but as the number of new toolboxes for a variety of fungi has grown, so too has the impact of fungi in the world of industrial biotechnology. Dr. Berka also highlights the importance of genomics to fungal biotechnology. Genomics has catalyzed our ability to mine fungal genomes for enzymes and metabolic pathways that are of value to industry and has allowed us to pursue greener approaches to the production of fuels and chemicals.

Understanding Fungal Biology

Over the last several years the JGI has sequenced and analyzed key industrial fungi, including strains of two of the most important industrial filamentous fungi—A. niger and T. reesei. ^6,26 These reference genomes provide the foundation from which we can resequence mutated strains and compare them to the wild type in order to associate phenotypes with genotypes. As the cost of sequencing decreases and throughput increases, it is increasingly attractive to resequence mutated strains and compare them to wildtype. ^27,28 In this issue, Koike and coauthors perform a detailed in silico comparison of the wild type Qm6a T. reesei strain with de novo assembled T. reesei RUT-C30 strain. ²⁹ This study identifies chromosomal rearrangements as well as a large number of mutations—some of which were discovered previously and reported in earlier publications—that were discovered using next generation sequencing or microarray technology; and it reports several additional novel mutations. ^30,31

Conversion of biomass to fermentable sugar continues to be an important process for biofuel production. The previous IB IN DEPTH Special Research Section on Fungal Biology highlighted a number of important aspects of this area of research. ^{32 –34} It is well known that multiple enzymatic activities are needed for the degradation of cellulose, and in this current issue an article by Chuave et al. elaborates on a method for kinetic modeling of enzymes needed for hydrolysis of cellulose. ^35,36

Moving forward, it is clear that genomics, modeling, and physiology are all important areas for fungal biology research,especially in the area of industrial biotechnology. To develop fully fungal bioprocesses, one must understand the genetic potential of an organism as well as its physiology, so models can be created that will drive the next generation of experiments and accelerate the development of sustainable and economical bioprocesses for the production of enzymes, renewable chemicals, and biofuels.