Dissertation

Exploring the metabolism and toxicity of amino sugars and 2-deoxyglucose in Streptomyces

Streptomyces are prolific producers of enzymes and secondary metabolites, including more than 50% of all clinical antibiotics. This makes them highly attractive for medical, biotechnological, and industrial purposes.

Author: C. Li
Date: 30 October 2024
Links: Thesis in Leiden Repository

Amino sugars, such as GlcN and GlcNAc, are vital for streptomycetes, as they are important carbon and nitrogen sources, and GlcNAc is involved in nutrient-mediated signalling that controls Streptomyces development and antibiotic production. In my thesis, the metabolism and toxicity of three glucose analogues, including GlcN, GlcNAc, and 2-deoxyglucose, are studied in Streptomyces coelicolor. We investigated the functions of two newly conserved proteins (RokL6 and NagS), aiming to work out their roles in GlcN(Ac) toxicity. We identified a transporter protein SCO1448, which is proposed to exports the toxic intermediates produced by GlcN and 2-deoxyglucose. Besides, we determined that NagS acts as a phosphosugar dehydratase, an activity has never been reported in any organism. With this, we propose a new model that explains the role of GlcNAc in streptomycetes morphological and chemical differentiation. We also found that pentose phosphate pathway is the key reaction for 2-deoxyglucose toxicity in S. coelicolor, shedding new lights on the mode of action of 2-deoxyglucose in bacteria.