Structural and functional analysis of proteins involved in natural product biosynthesis and morphological differentiation in Streptomyces

Xiao, X. (2020)

Doctoral Thesis

Streptomyces present a valuable platform for natural product discovery. Lugdunomycin is a novel angucycline-derived polyketide from Streptomyces sp QL37, with unprecedented skeleton and antimicrobial activity. This dissertation covers the research on the biosynthesis of this novel antibiotic and the developmental biology of Streptomyces. The data in this thesis have provided important new insights into the puzzle of lugdunomycin biosynthesis and the sporulation-specific cell division of Streptomyces. By means of molecular biology, structural biology, biochemical, chemical and bioinformatics approaches, we have uncovered the potential functions of the key enzymes, especially those encoded oxygenases (LugOI-LugOV) in lugdunomycin biosynthesis. Furthermore, we extensively studied the role of SsgB in Streptomyces development, that led us to the discovery of longitudinal cell division that support the predominant role of SsgB in the accurate positioning of the division site and the placement of the Z-ring.

• Streptomyces
• Lugdunomycin biosynthesis
• Oxygenases
• Enzymatic teamwork
• Developmental biology
• SsgB
• Cell division

• All authors: Xiao, X.
• Supervisor: Wezel, G.P. van
• Co-supervisor: Elsayed, S.S.
• Committee: Meijer, A.H.; Winde, J.H. de; Martin, N.I.; Masschelein, J.; Metsä-Ketelä, M.
• Qualification: Doctor (dr.)
• Awarding Institution: Institute of Biology Leiden (IBL), Faculty of Science, Leiden University
• Date: 2020-12-08
• Sponsorship: This work was supported by grant No. 201504910722 from China Scholarship Council.