PROCESS OPTIMIZATION FOR IMPROVED VITAMIN B₁₂ YIELD BY LACTIC ACID BACTERIAL FERMENTATION: A REVIEW

Abstract

Vitamin B₁₂ (cobalamin) is one of the most intriguing biomolecules in nutritional science, first identified as the anti-pernicious anemic factor and later recognized for its exceptionally complex structure and chemistry. Despite its vital role in human health supporting only two key enzymatic reactions, methionine synthase and (R)-methylmalonyl-CoA mutase, its biosynthesis occurred exclusively in selected prokaryotes and had never been naturally adopted by eukaryotes. Humans require only trace amounts of this vitamin, approximately 1 µg per day, yet global demand exceeded ten tons annually, largely fulfilled through microbial fermentation. Among various microbial producers, lactic acid bacteria (LAB) had gained attention due to their Generally Recognized as Safe (GRAS) status, probiotic benefits, and compatibility with food-grade fermentation systems. This review highlighted the historical milestones of vitamin B₁₂ research, outlined its physiological significance, and summarized the complex bacterial pathways responsible for its de novo formation. Furthermore, it discussed emerging strategies to enhance vitamin B₁₂ production using LAB grown in readily available dairy substrates, emphasizing process optimization, strain improvement and the potential for sustainable, cost-effective nutraceutical development.