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You searched for id:"oai:archiv.ub.uni-marburg.de:urn:nbn:de:hebis:04-z2018-0497". One record found.

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Philipps-Universität Marburg

1. Yu, Huili. Untersuchungen zur Entstehung und Metabolismus von zyklischen Dipeptiden in Aktinomyzeten sowie Anwendungen von pilzlichen Prenyltransferazen in der chemoenzymatischen Synthese.

Degree: PhD, Fachbereich Pharmazie, 2018, Philipps-Universität Marburg

Secondary metabolites originated from plants, bacteria and fungi constitute a large group of compounds, which are not directly related to the growth, development and reproduction of the organism. However, the producer can benefit from these metabolites to defend itself against natural enemies, competitors or environmental pressure. Furthermore, they often exhibit useful and interesting biological and pharmaceutical activities, which provide benefits to human health and life. For example, cyclodipeptides (CDPs) and their derivatives have gained increasing attention for their interesting and diverse pharmaceutical activities. Natural CDPs are mainly formed by nonribosomal peptide synthetases (NRPSs) or cyclodipeptide synthases (CDPSs). The CDP cores resulted from the NRPS or CDPS pathways are often further modified by varieties of tailoring enzymes leading to the formation of sophisticated natural products. The small size of CDPSs (200−300 residues) makes them genetically easily manipulated in synthetic biology. In the first project of this thesis, a cooperation project with Jing Liu, nine new CDPS genes from eight Streptomyces strains were functionally characterized after cloning into pET28a vector and expressing in E. coli. The products were analyzed on LC-MS and then isolated for NMR analysis. The products were identified as tryptophan-containing cyclodipeptides (cWXs) that are the most common precursors of diketopiperazines (DKPs) with pharmaceutical interest, due to the various modification possibilities on the indole ring. The nine identified CDPSs include six specific CDP synthases consisting of one cWL synthase, two cWP synthases and three new cWW synthases as well as three unspecific CDPSs producing several products with cWA or cWY as the major cyclodipeptide. Total product yields of CDPs were calculated based on HPLC analysis to be 46 to 211 mg/L E. coli culture. Our findings represent rare examples of cWXs derived from CDPS pathways in actinobacteria. This study also provides a valid experimental basis for further combination of CDPSs with other tailoring enzymes in biosynthesis of interesting compounds. The three identified cWW synthases from Streptomyces purpureus NRRL B-5737, Streptomyces lavendulae NRRL B-2774, and Streptomyces xanthophaeus NRRL B-5414 are genetically associated with a putative cytochrome P450. The three P450 homologues share sequence identities of more than 75% with each other on the amino acid level, indicating same or very similar function. As a representative, the function of P450NB5737 from S. purpureus was identified by heterologous expression in Streptomyces coelicolor and in vitro assays with the recombinant protein produced in E. coli. Isolation and structure elucidation confirmed that P450NB5737 catalyzes the transfer of a guanine moiety onto the indole ring of cWW via a C–N bond, leading to unprecedented adducts of cyclodipeptide with a nucleobase. This represents one additional example of rare P450 enzymes catalyzing the coupling of two different substrates. Besides… Advisors/Committee Members: Li, Shu-Ming (advisor).

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APA (6th Edition):

Yu, H. (2018). Untersuchungen zur Entstehung und Metabolismus von zyklischen Dipeptiden in Aktinomyzeten sowie Anwendungen von pilzlichen Prenyltransferazen in der chemoenzymatischen Synthese. (Doctoral Dissertation). Philipps-Universität Marburg. Retrieved from http://archiv.ub.uni-marburg.de/diss/z2018/0497

Chicago Manual of Style (16th Edition):

Yu, Huili. “Untersuchungen zur Entstehung und Metabolismus von zyklischen Dipeptiden in Aktinomyzeten sowie Anwendungen von pilzlichen Prenyltransferazen in der chemoenzymatischen Synthese.” 2018. Doctoral Dissertation, Philipps-Universität Marburg. Accessed November 20, 2018. http://archiv.ub.uni-marburg.de/diss/z2018/0497.

MLA Handbook (7th Edition):

Yu, Huili. “Untersuchungen zur Entstehung und Metabolismus von zyklischen Dipeptiden in Aktinomyzeten sowie Anwendungen von pilzlichen Prenyltransferazen in der chemoenzymatischen Synthese.” 2018. Web. 20 Nov 2018.

Vancouver:

Yu H. Untersuchungen zur Entstehung und Metabolismus von zyklischen Dipeptiden in Aktinomyzeten sowie Anwendungen von pilzlichen Prenyltransferazen in der chemoenzymatischen Synthese. [Internet] [Doctoral dissertation]. Philipps-Universität Marburg; 2018. [cited 2018 Nov 20]. Available from: http://archiv.ub.uni-marburg.de/diss/z2018/0497.

Council of Science Editors:

Yu H. Untersuchungen zur Entstehung und Metabolismus von zyklischen Dipeptiden in Aktinomyzeten sowie Anwendungen von pilzlichen Prenyltransferazen in der chemoenzymatischen Synthese. [Doctoral Dissertation]. Philipps-Universität Marburg; 2018. Available from: http://archiv.ub.uni-marburg.de/diss/z2018/0497

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