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Scientists from the Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences have developed a lipid-rich mutant strain of Saccharomyces cerevisiae using a high-throughput, label-free screening technique, opening new possibilities for microbial production of palmitoleic acid—an omega-7 fatty acid with proven anti-inflammatory and metabolic benefits.

The findings, published in , address a critical challenge in producing palmitoleic acid, which is scarce in conventional oil crops.

Currently, the fatty acid is primarily sourced from plants like sea buckthorn and macadamia, whose cultivation is limited by geographic constraints and low yields. While S. cerevisiae naturally produces palmitoleic acid, its low total lipid content has blocked industrial-scale applications.

To overcome this, the research team used a combined mutagenesis approach—employing zeocin, an antibiotic-based mutagen, and Atmospheric and Room Temperature Plasma (ARTP)—to create a diverse library of yeast mutants. They then deployed FlowRACS, a Raman flow cytometry system, to select live yeast cells with elevated lipid levels by analyzing their intrinsic single-cell Raman spectra, eliminating the need for chemical stains or genetic reporters.

This method identified the mutant strain MU2R48, which achieved a lipid content of 40.26%—a 30.85% increase over its parental strain SC018—while maintaining similar biomass production.

"FlowRACS enables label-free, non-invasive selection of lipid-producing cells at single-cell resolution," said Ji Xiaotong, co-first author of the study, and a postdoctoral fellow at QIBEBT. "It directly connects phenotype to function without requiring genetic modification or chemical labeling."

Multi-omics analysis revealed that MU2R48's enhanced lipid accumulation stems from coordinated metabolic changes: increased activity in glycolysis, ethanol degradation, and the pentose phosphate pathway boosted production of acetyl-CoA and NADPH—key building blocks for fatty acid synthesis—while fatty acid breakdown pathways were suppressed.

This metabolic reshaping illustrates how targeted mutagenesis and advanced screening can collaboratively optimize microbial production. The mutant strain provides a potential foundation for the biosynthesis of palmitoleic acid, as noted by the team.

The study underscores the value of combining advanced cell-sorting technologies with multi-omics analysis to develop high-performance microbial strains without transgenic methods.