Studies in enantioselective microbial deuteration

Area of Science:

• Biocatalysis and Isotope Labeling
• Synthetic Organic Chemistry
• Microbial Biotechnology

Background:

• Deuterium-labeled compounds are crucial for medicinal and analytical applications.
• Current methods for achieving high levels of isotopic labeling can be expensive and complex.
• Exploring diverse microbial resources offers potential for more economical isotope labeling strategies.

Purpose of the Study:

• To develop economical methods for reductive microbial deuteration with high isotopic labeling.
• To evaluate various yeast strains and inexpensive carbon sources for deuterium incorporation.
• To assess the utility of molecular rotational resonance spectroscopy for process evaluation.

Main Methods:

• Utilized a strategy of alpha-hydrogen exchange followed by microbial reduction for deuteration.
• Employed specific yeast strains like Saccharomyces cerevisiae MBG5177 and Pichia pastoris X-33.
• Used methanol-d4 as an affordable deuterated carbon source.
• Applied molecular rotational resonance spectroscopy (MRR) for analysis of deuteration levels and enantiopurity.

Main Results:

• >95% backbone perdeuteration achieved for chiral building blocks without loss of enantioselectivity.
• Saccharomyces cerevisiae MBG5177 showed superior performance over baker's yeast for (2-2H1)solketal synthesis.
• Pichia pastoris X-33 demonstrated >95% deuteration using methanol-d4.
• MRR accurately measured site-specific deuteration and enantiopurity, simplifying process evaluation.

Conclusions:

• Diverse microbial strains, not traditionally used in synthesis, are effective for isotope labeling.
• Economical microbial deuteration methods are feasible using selected yeast strains and affordable deuterated sources.
• Molecular rotational resonance spectroscopy is a valuable tool for analyzing deuterium-labeling processes.
• This work advances isotope labeling and biocatalysis with implications for research and industry.