Abstract:Lactococcus lactis, a representative lactic acid bacterium widely used in the food industry, is a generally recognized as safe organism characterized by a relatively simple metabolic network, a small genome, and the absence of endotoxins. Traditionally categorized as a facultative anaerobe relying primarily on fermentation, L. lactis can switch to respiratory metabolism under conditions of heme supplementation and oxygen availability. With the rapid development of synthetic biology, potential use of L. lactis as a safe chassis microorganism is increasingly recognized; its metabolic regulatory mechanisms, particularly those related to aerobic respiration, have attracted interest. This review summarizes recent advances in elucidating heme-dependent L. lactis aerobic respiration. It focuses on the effects of oxygen on respiratory metabolism, composition and mechanisms of the aerobic respiratory chain, the central role of heme in aerobic respiration, and related metabolic processes involving heme, such as carbon and nitrogen metabolism, in L. lactis. The potential application of aerobic respiration in L. lactis for food fermentation and biomedicine is also discussed in this review. This review provides a reference for future collaborative research on the aerobic respiration and fermentation of L. lactis and its industrial applications.