PhD Student: Sara Foiadelli (ORCID n. 0009-0005-6158-4999)
Supervisor: Prof. Francesco Molinari (DeFENS)
Co-tutor: Dr. Davide Berlanda (Company tutor)
Dean: Prof. Diego Mora
Research area: Chemistry and Biochemistry
Research topic
Biotechnological processes for the transformation of agri-food residues into added-value molecules
Project Synopsis
Sustainable bioprocesses for plant secondary metabolite biotransformation
The demethylation of natural products has the potential to generate derivatives with an enhanced bioactivity, but chemical methods are poorly selective.1 The selective demethylation of methoxy-compounds has been reported in Priestia megaterium, operated by the CYP102A1 encoded BM3-p450 cytochrome.2 In this project the P. megaterium DSM32 strain will be used for the selective demethylation and subsequent glycosylation of methoxy-containing natural products for the generation of bioactive compounds with improved properties. Different strategies will be pursued: i) fermentation will be tested using different waste residues and growth media to enhance the sustainability of the process; ii) immobilized whole cells will be used in flow reactors and rotating bed reactors to improve their efficiency; iii) the enzymes involved in the bioconversion will be produced as recombinant proteins and characterized.
Finally, semi-rational protein engineering will be applied to Cytochrome P450 BM3 monooxygenase from Bacillus megaterium. This strategy will be undertaken to design and produce mutants with improved efficiency.
1) Harvey AL, Edrada-Ebel R, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov. 2015 Feb;14(2):111-29. doi: 10.1038/nrd4510
2) Ponzone C, Berlanda D, Donzelli F, Acquati V, Ciulla R, Negrini A, Rovati M, Evangelista D, Fata E, Ciceri D, Perterlongo F, Cabri W. Biotransformation of colchicinoids into their corresponding 3-O-glucosyl derivatives by selected strains of Bacillus megaterium. Mol Biotechnol. 2014 Jul;56(7):653-9. doi: 10.1007/s12033-014-9741-5.
Project keywords
biocatalysis, fermentation, flow chemistry, natural bioactives.
Contacts
University of Milan, Department of Food, Environmental and Nutritional Sciences (DeFENS), Via Mangiagalli 25, 20133 Milan, Italy; sara.foiadelli@unimi.it
Collaborations
Dr. Davide Berlanda, Dr. Otto Bazzana (Biotechnology Lab at Indena SpA)
Sponsor
Fellowship sponsor: Indena SpA
Publications
Cocorullo, M.; Bettoni, C.; Foiadelli, S.; Stelitano, G. Moles of Molecules against Mycobacterium abscessus: A Review of Current Research. Future Pharmacol. 2023, 3, 637–663. https://doi.org/10.3390/futurepharmacol3030041