Development of a versatile and conventional technique for gene disruption in filamentous fungi based on CRISPR-Cas9 technology

Zheng, Yanmei; Lin, Fu-Long; Gao, Hao; Zou, Gen; Wang, Gao-Qian; Chen, Guodong; Zhou, Zhihua; Yao, Xin‐Sheng; Hu, Dan

doi:10.1038/s41598-017-10052-3

Cited by 65 publications

(59 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Genome editing using CRISPR-Cas9 is reported in various fungi and can be used for pathway engineering via gene inactivation [32,33]. Talaromyces atroroseus is an unexplored fungal species that synthesizes ZG-1494a, a PAF acetyltransferase inhibitor.…”

Section: Pathway Engineeringmentioning

confidence: 99%

Strategies for Engineering Natural Product Biosynthesis in Fungi

Skellam

2019

Trends in Biotechnology

View full text Add to dashboard Cite

Fungi are a prolific source of bioactive compounds, some of which have been developed as essential medicines and life-enhancing drugs. Genome sequencing has revealed that fungi have the potential to produce considerably more natural products (NPs) than are typically observed in the laboratory. Recently, there have been significant advances in the identification, understanding, and engineering of fungal biosynthetic gene clusters (BGCs). This review briefly describes examples of the engineering of fungal NP biosynthesis at the global, pathway, and enzyme level using in vivo and in vitro approaches and refers to the range and scale of heterologous expression systems available, developments in combinatorial biosynthesis, progress in understanding how fungal BGCs are regulated, and the applications of these novel biosynthetic enzymes as biocatalysts. Fungal NPs and Human Health NPs (see Glossary) or NP derivatives represented 25% of all FDA-approved drugs in the years spanning 1981 to 2014 [1]. Fungi are prolific producers of some of these important drugs, such as antibiotics (e.g., penicillin, pleuromutilin), cholesterol-lowering drugs (e.g., lovastatin, compactin), and immunosuppressants (e.g., mycophenolic acid, cyclosporine). Fungal NPs have many biological activities, ranging from carcinogens (e.g., aflatoxins), deadly toxins (e.g., a-amanitin), and industrial fungicides (e.g., strobilurin) to food colorants (e.g., azaphilones), hormones (e.g., gibberellin), and psychedelics (e.g., psilocybin) [2,3]. In nature, these NPs serve to protect fungi from predators (e.g., insects), UV radiation, and competition from other microorganisms and have evolved to secure their survival in niche habitats; they just happen to have had a profound effect on human health. The broad spectrum of biological activities reflects their structural diversity, which arises from their biosynthetic classification (e.g., polyketides, peptides, terpenes, alkaloids) (Figure 1). The complexity of fungal secondary metabolism presents numerous challenges for traditional drug discovery. Fungi often produce NPs at very low levels or in response to specific environmental cues that are difficult to reproduce in the laboratory [4]. The prominence of NPs in the pharmaceutical industry and re-emerging interest in NPs as lead structures in drug discovery [5] require methods to engineer improved NP analogs and activate silent biosynthetic pathways. In recent years there have been substantial advances in strategies for engineering fungal NP biosynthesis (Figure 2, Key Figure), which are highlighted in this review. These strategies can be divided into three broad categories: (i) inducing global transcriptional perturbations (e.g., through epigenetic modifications or the overexpression of global transcriptional regulators), which effectively 'awakens' the biosynthetic machinery and often affects multiple pathways resulting in the production of a variety of NPs, but is unpredictable and difficult to control Highlights

show abstract

Section: Pathway Engineeringmentioning

confidence: 99%

Strategies for Engineering Natural Product Biosynthesis in Fungi

Skellam

2019

Trends in Biotechnology

View full text Add to dashboard Cite

show abstract

“…The rapid development of bioinformatics infrastructures has facilitated a boom in Asian fungal genomics in the region [19,82]. In addition, several mycological breakthroughs have been published by Asian scientists, such as massive decoding of non-model fungal genomes [19,20] and successful application of Agrobacterium-mediated fungal transformation and CRISPR/CAS9 systems [83]. While China leads the way, many governments and private sectors in Asia are investing billions of dollars into genetics research.…”

Section: Genomicsmentioning

confidence: 99%

The rise of mycology in Asia

Hyde¹,

Chethana²,

Jayawardena³

et al. 2020

ScienceAsia

View full text Add to dashboard Cite

Mycology was a well-studied discipline in Australia and New Zealand, Europe, South Africa and the USA. In Asia (with the exception of Japan) and South America, the fungi were generally poorly known and studied, except for the result of forays from some American and European mycologists. However, in the last 20 years, the situation has changed. With the development of Asian economies, the funding for science research and development has greatly increased. Mycological research has also diversified in many fields. Many studies have focused on applied aspects and new journals and websites have been established as a platform for Asian mycologists to publish their research. This paper will briefly review the history of the study of fungi in Asia and then discuss how it advanced during the last two decades. It will examine the current situation using case studies in plant pathogens, terrestrial saprobes, aquatic fungi, evolution studies, genomics and applied mycology and biotechnology. Finally, it will suggest research that is needed in the future.

show abstract

“…The CRISPR-Cas system was selected by the journal Science as its 2015 Breakthrough of the Year (McNutt, 2015); you can read about the latest developments in the 'CRISPR revolution' topic page written by Jon Cohen (a staff writer for Science) at this URL: http://www.sciencemag.org/topic/crispr. Gene editing technologies have been developed for application to animals (Dunn & Pinkert, 2014), plants (Mohanta et al, 2017) and fungi (Nødvig et al, 2015;Chen et al, 2017;Pudake et al, 2017;Zheng et al, 2017), and these publications all make fascinating reading. Anzalone et al (2019) describe a technique they call prime editing (or search-and-replace genome editing) as being:…”

Section: Manipulating Genomes: Gene Editingmentioning

confidence: 99%

21st century miniguide to fungal biotechnology

et al. 2019

View full text Add to dashboard Cite

Realising the biotechnological potential of fungi requires full appreciation of the molecular biology and genetics of this kingdom. We review recent advances in our understanding of fungal genetic structure as it might influence biotechnology; including introns, alternative splicing of primary transcripts, transposons (transposable elements, or TEs), heterokaryosis, ploidy and genomic variation, sequencing, annotation and comparison of fungal genomes, and gene editing. We end by indicating under-researched, but unique, aspects of fungal cell biology that offer opportunities for developing new strategies to manage the activities of fungi to our benefit. As a closing example, we discuss the potential of bioengineering fungi specifically for bioremediation of plastic wastes.

show abstract

Development of a versatile and conventional technique for gene disruption in filamentous fungi based on CRISPR-Cas9 technology

Cited by 65 publications

References 28 publications

Strategies for Engineering Natural Product Biosynthesis in Fungi

Strategies for Engineering Natural Product Biosynthesis in Fungi

The rise of mycology in Asia

21st century miniguide to fungal biotechnology

Contact Info

Product

Resources

About