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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Publication date: 2018
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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.