An Investigation of Inhibitory Mechanisms of Flavonoids Against Bacterial Enoyl-reductase

Author(s)

Puneet MannFollow

Presentation Type

Oral Presentation

Keywords

FabI, reversibility, flavonoids, inhibitors, ACP enoyl reductase, antibiotic resistance

Major

Biology

Abstract

Flavonoids are naturally occurring compounds found in plants. Flavonoids have a general structure of 15 carbons arranged as two phenyl groups and a heterocyclic ring connected by a carbon chain. Although flavonoids may have health benefits, minimal information exists about permanent inhibitory effects of flavonoids on protein activity and the resulting overall systemic effect on an organism. In particular, the enzyme FabI or enoyl-ACP reductase is responsible for catalyzing the last step of fatty acid elongation in bacteria and some flavonoid compounds have been found to inhibit this enzymatic step, resulting in the termination of bacterial fatty acid synthesis.

The goal of this project was to assess quercetin and catechin as potential reversible inhibitors of FabI, while triclosan served as a positive control. Research gleaned from literary review aided in the development of two hypotheses: 1) catechin and quercetin will display different FabI inhibition mechanisms, 2) catechin and quercetin are reversible inhibitors. Preliminary results collected from enzyme kinetics assays and spin column filtration, showed that both catechin and quercetin are reversible inhibitors. Data suggestive of quercetin’s reversibility is intriguing as it may point to new discoveries in drug therapy, while data showing catechin’s reversibility directly contradicts published literature. Previous experiments in the Joyner lab suggested that quercetin may form a permanent covalent bond with cysteine residues, while other articles have indicated that the covalent bond is continuously being broken and reformed. Results from this thesis provide support for the latter regarding quercetin’s inhibitory properties and will require further study to confirm its classification as a reversible inhibitor. Data suggestive of quercetin’s reversibility is intriguing as it may point to new discoveries in drug therapy, while data showing catechin’s reversibility directly contradicts published literature.

Faculty Mentor

Dr. Matt Joyner

Funding Source or Research Program

Undergraduate Research Fellowship

Presentation Session

Session A

Location

Black Family Plaza Classroom 188

Start Date

25-3-2022 4:15 PM

End Date

25-3-2022 4:30 PM

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Mar 25th, 4:15 PM Mar 25th, 4:30 PM

An Investigation of Inhibitory Mechanisms of Flavonoids Against Bacterial Enoyl-reductase

Black Family Plaza Classroom 188

Flavonoids are naturally occurring compounds found in plants. Flavonoids have a general structure of 15 carbons arranged as two phenyl groups and a heterocyclic ring connected by a carbon chain. Although flavonoids may have health benefits, minimal information exists about permanent inhibitory effects of flavonoids on protein activity and the resulting overall systemic effect on an organism. In particular, the enzyme FabI or enoyl-ACP reductase is responsible for catalyzing the last step of fatty acid elongation in bacteria and some flavonoid compounds have been found to inhibit this enzymatic step, resulting in the termination of bacterial fatty acid synthesis.

The goal of this project was to assess quercetin and catechin as potential reversible inhibitors of FabI, while triclosan served as a positive control. Research gleaned from literary review aided in the development of two hypotheses: 1) catechin and quercetin will display different FabI inhibition mechanisms, 2) catechin and quercetin are reversible inhibitors. Preliminary results collected from enzyme kinetics assays and spin column filtration, showed that both catechin and quercetin are reversible inhibitors. Data suggestive of quercetin’s reversibility is intriguing as it may point to new discoveries in drug therapy, while data showing catechin’s reversibility directly contradicts published literature. Previous experiments in the Joyner lab suggested that quercetin may form a permanent covalent bond with cysteine residues, while other articles have indicated that the covalent bond is continuously being broken and reformed. Results from this thesis provide support for the latter regarding quercetin’s inhibitory properties and will require further study to confirm its classification as a reversible inhibitor. Data suggestive of quercetin’s reversibility is intriguing as it may point to new discoveries in drug therapy, while data showing catechin’s reversibility directly contradicts published literature.