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University of Groningen Genetic engineering of Penicillium chrysogenum for the reactivation of biosynthetic pathways with potential pharmaceutical value Guzmán Chávez, Fernando

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University of Groningen

Genetic engineering of Penicillium chrysogenum for the reactivation of biosynthetic pathways

with potential pharmaceutical value

Guzmán Chávez, Fernando

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2018

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Guzmán Chávez, F. (2018). Genetic engineering of Penicillium chrysogenum for the reactivation of biosynthetic pathways with potential pharmaceutical value. University of Groningen.

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PROPOSITIONS

Genetic engineering of Penicillium chrysogenum

for the reactivation of biosynthetic pathways

with potential pharmaceutical value

1) A change in a single nucleotide of the sorA gene can silence or activate the complete biosynthetic pathway for sorbicilli-noids (Chapter 2). 2) Sorbicillinoid biosynthesis is regulated by SorR1 and SorR2, which orchestrate an auto induction mechanism (Chapter 3). 3) SorR1 is the main activator of the sorbicillinoid pathway while SorR2 and HdaA act as negative regulators (Chapter 3 and 4). 4) HdaA regulates the expression of PKS and NRPS genes and

promotes crosstalk between biosynthetic gene clusters (Chapter 4). 5) Deletion of seven putative candidate genes for the penicillin transporter did not affect penicillin production, but the de- letion of Pc22g00380 decreased the uptake of the precur-sors phenylacetic acid and phenoxyacetic acid (Chapter 5). 6) ”Awakening” of the sorbicillin gene cluster shows the poten-tial of this technology to elucidate other silenced biosyn-thetic gene clusters in Penicillium chrysogenum (all chapters). 7) A side project can convert into the main PhD project after effort and work, since you never know where the fortune will come from. 8) Weekends are the best time to work, especially when criti-cal equipments like “Lola” are available for running the key experiments.

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