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Updated: Jun 5, 2025

EPR Monitored Redox Titration of the Cofactors of Saccharomyces cerevisiae Nar1
Published on: November 26, 2014
A specialized role played by a redox cofactor.
Shengling Xie1,2, Lihan Zhang2,3
1Department of Chemistry, Zhejiang University, Hangzhou 310058, Zhejiang Province, China.
Nicotinamide adenine dinucleotide (NAD) is a building block for altemicidin biosynthesis. A novel enzyme using NAD and S-adenosylmethionine (SAM) creates the alkaloid structure, enabling studies on NAD-derived natural products.
Area of Science:
- Biochemistry
- Natural Product Biosynthesis
- Enzymology
Background:
- Nicotinamide adenine dinucleotide (NAD) is a crucial redox cofactor in cellular metabolism.
- Alkaloid natural products possess diverse biological activities and complex structures.
- Understanding biosynthetic pathways is key to natural product discovery and engineering.
Purpose of the Study:
- To elucidate the biosynthetic pathway of the alkaloid altemicidin.
- To identify the enzymes involved in altemicidin formation.
- To explore the use of NAD as a precursor in natural product biosynthesis.
Main Methods:
- Biosynthetic pathway investigation using enzymatic assays.
- Identification and characterization of a novel pyridoxal pyrophosphate (PLP)-dependent enzyme.
- Analysis of substrate utilization (NAD and S-adenosylmethionine (SAM)).
Main Results:
- β-Nicotinamide adenine dinucleotide (NAD) serves as a direct building block for altemicidin.
- A unique PLP-dependent enzyme was identified as the key catalyst.
- The enzyme utilizes both NAD and S-adenosylmethionine (SAM) to construct the bicyclic alkaloid scaffold.
Conclusions:
- The biosynthesis of altemicidin involves a novel enzymatic mechanism utilizing NAD.
- This discovery expands the known roles of NAD in secondary metabolism.
- Opens new avenues for the biosynthesis of other NAD-derived natural products.
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