Off-campus UNL users: To download campus access dissertations, please use the following link to log into our proxy server with your NU ID and password. When you are done browsing please remember to return to this page and log out.
Non-UNL users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Biological Functions of Polycyclic Tetramate Macrolactams from Lysobacter enzymogenes
Abstract
Lysobacter species are gliding Gram-negative bacteria and prolific producers of new bioactive natural products which are largely underexplored. So far, several classes of structurally distinct and biologically active natural products have been isolated from Lysobacter. This dissertation will focus on the polycyclic tetramate macrolactams (PoTeM) from Lysobacter enzymogenes, including HSAF (heat stable antifungal factor), alteramides, and their 3-dehydroxyl analogs.The work described in Chapter 2 discovered that Lysobacter, a predator of fungi, has evolved a smart mechanism in which a “wall opener” (LPMO, lytic polysaccharide monooxygenase) and “warheads” (HSAF and analogs) are packaged together into a lethal cargo (OMV, outer membrane vesicle) to coordinately kill the fungal prey. LPMO is a lytic enzyme that oxidatively cleaves chitin of fungal cell walls and was identified and characterized in Lysobacter for the first time. OMV is produced by Gram-negative bacteria under certain circumstances, often in response to stress-related conditions.Building upon this previously uncharacterized synergistic strategy, we identified a major facilitator superfamily (MFS) transporter gene hsaf-orf1 which might assist this process. This work is described in Chapter 3. Gene hsaf-orf1 is the first open reading frame in HSAF biosynthetic gene cluster (BGC). Results obtained from gene deletion and labeled substrate uptake showed that the role of hsaf-orf1 is not extracellular export of HSAF and analogs. Instead, it plays an important role in production of HSAF and analogs, through controlling the import of small sugars, such as glucose or N-acetylglucosamine (the ultimate product of chitin hydrolysis), that may serve as nutrients and signals.HSAF and analogs have attracted lots of attention in the past decade. However, very little is known about the relations between their physiological functions and the downstream genes of HSAF BGC. In Chapter 4, we have investigated the potential relations through generating mutants of genes hsaf-orfD and hsaf-orfE and examining their impacts on growth of L. enzymogenes. The results suggested that these two genes are related to some other biological functions of L. enzymogenes instead of the oxidative stress modulation.
Subject Area
Chemistry|Biochemistry|Molecular biology
Recommended Citation
Yue, Huan, "Biological Functions of Polycyclic Tetramate Macrolactams from Lysobacter enzymogenes" (2022). ETD collection for University of Nebraska-Lincoln. AAI29167481.
https://digitalcommons.unl.edu/dissertations/AAI29167481