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Published on: December 7, 2021
Terminal Alkyne Biosynthesis in Marine Microbes
1University of California, Berkeley, CA, United States.
Synthetic biology offers new pathways to terminal alkynes, crucial for drug discovery and materials. Researchers are exploring marine natural products to understand and engineer this vital chemical synthesis.
Area of Science:
- Biochemistry
- Synthetic Biology
- Natural Products Chemistry
Background:
- Terminal alkynes are versatile functional groups with applications in material science, pharmaceuticals, and chemical biology.
- Synthetic routes to terminal alkynes are highly sought after but remain underexplored.
- Marine natural products and their biosynthetic gene clusters (e.g., jamaicamide B, carmabin A) have opened new avenues for understanding terminal alkyne biosynthesis.
Purpose of the Study:
- To provide an overview of recent advancements in understanding the biosynthetic machinery for terminal alkyne synthesis.
- To detail methodologies for elucidating terminal alkyne biosynthetic pathways.
- To discuss strategies for discovering new enzymes and metabolites involved in terminal alkyne production.
Main Methods:
- Elucidating biosynthetic mechanisms via heterologous expression, protein purification, and in vitro biochemical assays.
- Utilizing an in vivo reporting system to characterize membrane-bound desaturase/acetylenase enzymes.
- Employing click chemistry for the identification and quantification of terminal alkyne-containing metabolites.
Main Results:
- Established methods for characterizing enzymes involved in terminal alkyne formation.
- Demonstrated the utility of heterologous expression and in vitro assays for pathway elucidation.
- Showcased click chemistry as a tool for metabolite discovery in microbial systems.
Conclusions:
- Significant progress has been made in understanding and engineering terminal alkyne biosynthesis.
- Further research is needed to address current challenges and explore future directions in the field.
- The integration of synthetic biology, biochemistry, and natural product discovery holds great promise for accessing novel terminal alkyne compounds.
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Biosynthesis of Lipids
Biosynthesis in Bacteria
Preparation of Alkynes: Alkylation Reaction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
Preparation of Alkynes: Dehydrohalogenation
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
Alkynes to Carboxylic Acids: Oxidative Cleavage

