Synthetic biology of fungal natural products

Mattern, Derek J.; Valiante, Vito; Unkles, Shiela E.; Brakhage, Axel A.

doi:10.3389/fmicb.2015.00775

Cited by 34 publications

(16 citation statements)

References 74 publications

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“…Fungi have also been widely used for the biotechnological production of enzymes and other proteins and a variety of primary and secondary metabolites including organic acids, pigments, antibiotics, hormones and other pharmaceutical compounds (Meyer et al, 2016a). They likewise hold great promise as organisms to be used in synthetic biology to engineer and control the production of existing and novel compounds with commercial applications (Paddon and Keasling, 2014;Mattern et al, 2015;Boecker et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

FungalBraid: A GoldenBraid-based modular cloning platform for the assembly and exchange of DNA elements tailored to fungal synthetic biology

Hernanz-Koers

Gandía

Garrigues

et al. 2018

Fungal Genetics and Biology

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Current challenges in the study and biotechnological exploitation of filamentous fungi are the optimization of DNA cloning and fungal genetic transformation beyond model fungi, the open exchange of ready-to-use and standardized genetic elements among the research community, and the availability of universal synthetic biology tools and rules. The GoldenBraid (GB) cloning framework is a Golden Gate-based DNA cloning system developed for plant synthetic biology through Agrobacterium tumefaciens-mediated genetic transformation (ATMT). In this study, we develop reagents for the adaptation of GB version 3.0 from plants to filamentous fungi through: (i) the expansion of the GB toolbox with the domestication of fungal-specific genetic elements; (ii) the design of fungal-specific GB structures; and (iii) the ATMT and gene disruption of the plant pathogen Penicillium digitatum as a proof of concept. Genetic elements domesticated into the GB entry vector pUPD2 include promoters, positive and negative selection markers and terminators. Interestingly, some GB elements can be directly exchanged between plants and fungi, as demonstrated with the marker hph for Hyg or the fluorescent protein reporter YFP. The iterative modular assembly of elements generates an endless number of diverse transcriptional units and other higher order combinations in the pDGB3α/pDGB3Ω destination vectors. Furthermore, the original plant GB syntax was adapted here to incorporate specific GB structures for gene disruption through homologous recombination and dual selection. We therefore have successfully adapted the GB technology for the ATMT of fungi. We propose the name of FungalBraid (FB) for this new branch of the GB technology that provides open, exchangeable and collaborative resources to the fungal research community.

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Section: Introductionmentioning

confidence: 99%

FungalBraid: A GoldenBraid-based modular cloning platform for the assembly and exchange of DNA elements tailored to fungal synthetic biology

Hernanz-Koers

Gandía

Garrigues

et al. 2018

Fungal Genetics and Biology

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“…Chemistry in a cell makes use of biosynthetic machinery of plants, microorganisms, and fungi 36 to produce NPs derivatives with therapeutic interest. NPs have already provided myriad of human medicines, including antibiotics, antifungals, antitumors, immunosuppressants, and cholesterol-lowering agents.…”

Section: Mining Nps Spacementioning

confidence: 99%

Synthetic biology for pharmaceutical drug discovery

Trosset¹,

Carbonell²

2015

DDDT

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Synthetic biology (SB) is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell–cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity.

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“…Over the decades, metabolic engineering and synthetic biology gained momentum in white biotechnology . The metabolic engineering and synthetic biology strategies led to enhanced production of endogenous and heterologous metabolites . The production of these metabolites cause toxicity in cells and also increases the pressure on the cell membrane .…”

Section: Introductionmentioning

confidence: 99%

“…1 The metabolic engineering and synthetic biology strategies led to enhanced production of endogenous and heterologous metabolites. [2][3][4][5] The production of these metabolites cause toxicity in cells 6 and also increases the pressure on the cell membrane. 7 The accumulation of these toxic metabolites can damage the cell membrane.…”

Section: Introductionmentioning

confidence: 99%

Identification of effective membrane efflux transporters against β‐amyrin through molecular docking approach

Ahmed

Sehgal

Tahir

et al. 2019

J of Chemical Tech & Biotech

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BACKGROUND Metabolic engineering techniques in microorganisms can produce high‐value complex metabolites. However, this efficiency was frequently hampered by toxic‐compounds produced due to the engineering of foreign genes. Comparatively, to other strategies, the efflux transporter engineering strategy is efficient to create a pulling effect at the downstream of the biosynthetic pathway, generally enhancing the cultural vitality and the total production yields due to which wild strains can withstand toxic compounds. However, it was difficult to select hundreds of transporters for the possible efflux of β‐amyrin. Thus, in silico approaches were used to explore the binding sites of the transporters and identify the stable binding patterns of transporters for the possible efflux of β‐amyrin. RESULTS A total 111 transporters were shortlisted having the ability to transport different compounds. Molecular docking analyses elucidated that YajR, UraA, GlcPse, and LeuT, transporters have strong binding affinities against β‐amyrin having least binding energies of −13.6, −13.4, −12.2, and − 11.9 kcal/mol, respectively. CONCLUSION For the first time, it was observed that the mentioned top‐ranked transporters might be the better option to efflux β‐amyrin for being effectively bound within the enclosed active site. These novel findings based on computational docking analyses may be momentous to enhance the metabolites production in the microorganism. © 2019 Society of Chemical Industry

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Synthetic biology of fungal natural products

Cited by 34 publications

References 74 publications

FungalBraid: A GoldenBraid-based modular cloning platform for the assembly and exchange of DNA elements tailored to fungal synthetic biology

FungalBraid: A GoldenBraid-based modular cloning platform for the assembly and exchange of DNA elements tailored to fungal synthetic biology

Synthetic biology for pharmaceutical drug discovery

Identification of effective membrane efflux transporters against β‐amyrin through molecular docking approach

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