Background and aim Difucosyllactose (Di‐FL) has strong antimicrobial activity against various pathogens, including group B Streptococcus, identified as the leading cause of neonatal sepsis. In this study, we sought to develop Escherichia coli as a microbial cell factory for efficiently producing Di‐FL as well as 2′‐fucosyllactose (2′‐FL), the most abundant fucosylated oligosaccharide in human milk, by utilizing the salvage guanosine 5′‐diphosphate (GDP)‐l‐fucose biosynthetic pathway. Main methods and major results The biosynthetic pathway for producing fucosylated oligosaccharides via the salvage pathway requires two enzymes, l‐fucokinase/GDP‐l‐fucose phosphorylase (FKP) from Bacteroides fragilis and α‐1,2‐fucosyltransferase (FucT2) from Helicobacter pylori. To decrease the intracellular accumulation of 2′‐FL while increasing substrate accessibility to FKP and FucT2, we evaluated whether extracellular secretion of FKP and FucT2 would enhance the production of fucosylated oligosaccharides. Among various engineered strains constructed in this study, the ΔLFAR‐YA/FF+P‐PLA2 strain expressing phospholipase A2 (PLA2) from Streptomyces violaceoruber, whose native signal peptide was replaced with the PelB signal peptide (P‐PLA2), could secrete both FKP and FucT2 into the culture medium. Notably, it was observed that FKP and FucT2 present in the extracellular fraction could catalyze the synthesis of Di‐FL from lactose and fucose. As a result, a batch fermentation with the ΔLFAR‐YA/FF+P‐PLA2 strain resulted in the production of 1.22 ± 0.01 g L−1 Di‐FL and 0.47 ± 0.01 g L−1 2′‐FL, whereas the control strain could only produce 0.65 ± 0.01 g L−1 2′‐FL. Conclusions and implications This study highlights the benefits of extracellular secretion of enzymes to improve biotransformation efficiency, as the transport of substrates and/or products across the cell membrane is limited.

Interaction between dipoles often emerges intriguing physical phenomena, such as exchange bias in the magnetic heterostructures and magnetoelectric effect in multiferroics, which lead to advances in multifunctional heterostructures. However, the defect-dipole tends to be considered the undesired to deteriorate the electronic functionality. Here, we report deterministic switching between the ferroelectric and the pinched states by exploiting a new substrate of cubic perovskite, BaZrO 3 , which boosts square-tensile-strain to BaTiO 3 and promotes four-variants in-plane spontaneous polarization with oxygen vacancy creation. First-principles calculations propose a complex of an oxygen vacancy and two Ti 3+ ions coins a charge-neutral defect-dipole. Cooperative control of the defect-dipole and the spontaneous polarization reveals three types of in-plane polar states characterized by biased/pinched hysteresis loops. Furthermore, we experimentally demonstrate that three electrically controlled polar-ordering states lead to switchable and non-volatile dielectric states for application of non-destructive electro-dielectric memory. This discovery opens a new route to develop functional materials via manipulating defect-dipoles and offers a novel platform to advance heteroepitaxy beyond the prevalent perovskite substrates.