Continuous-flow biocatalysis is gaining attention for the synthesis of highly valuable pharmaceuticals and fine chemicals. The integrated approach combines the high activity and selectivity of biocatalysts with the superior efficiency in mass and heat transfer of continuous-flow systems. Considerable progress has been made in the continuous-flow biocatalysis, but there are only a few reviews on the specific challenges and strategies encountered in continuous-flow reactions involving different biocatalysts. This review aims to present a general overview of the implementation of various biocatalysts in continuous-flow systems for synthetic applications, and their specific issues and strategies associated with each category were discussed in detail. Future directions for biocatalysis in continuous flow, including current problems and potential strategies were proposed to offer insights and support for the advancement of continuous-flow biocatalysis. Recent advances in continuous-flow biocatalysis were summarized according to the types of biocatalysts involved, encompassing single enzymes, multienzyme catalysts, whole-cell catalysts, metal-enzymatic catalysts, and organo-enzymatic catalysts, along with their combination with photocatalysis and electrocatalysis. The main challenges faced by diverse biocatalysts in continuous-flow processes have been systematically discussed, including poor substrate solubility with lipases, low oxygen availability for oxidoreductases, cofactor regeneration, catalyst leaching, as well as incompatibility problems in multi-enzyme cascade catalysis, and biocatalysis coupling with chemo-catalysis or other catalysis. Various strategies have been developed for addressing these challenges, such as construction of continuous-flow biphasic systems, design of self-sufficient biocatalysts, easy preparation of bioreactors mediated by fusion-tag. Future researches should focus on machine learning-assisted protein engineering and materials design, as well as computer-aided optimization of continuous-flow cascade systems, to reduce enzyme activity loss due to immobilization, and address mismatches between multiple enzymes and chemo-/photocatalysts in cascade processes, thereby developing sustainable, efficient, and industrially viable processes.

To explore the effects of microbial community changes on the key flavor substances in base Baijiu, this study analyzed the microbiome of the pre-pit fermentation grains using high-throughput sequencing technology and determined the flavor substances of the base Baijiu by GC-FID. The results showed the microbial community changed dynamically between the different rounds, as well as bacteria and fungi displayed different succession patterns. Next, the variations of skeletal flavor substances in the base Baijiu were analyzed by multiomics, and it was found that alcohols, acids, and esters were the most abundant, accounting for 88.16–98.87% of the total flavor substances, and decreased with the increase of the rounds. By calculating the Spearman coefficient, it was found that microorganisms such as Acinetobacter, Oceanobacillus, Saccharomyces, and Byssochlamys were significantly correlated with the n-Propano and 2,3-Butanediol and other components in the base Baijiu. Finally, 15 flavor substances such as Acetaldehyde, Propionaldehyde, and Isobutyraldehyde were identified as key substances by OAV analysis. This study is the first to reveal the potential association between the microbial community of pre-pit fermentation grains and flavor of base Baijiu and has the benefit of improving the quality of base Baijiu.

A complete and efficient utilization of sweet sorghum stalk including sweet sorghum juice (SSJ) and sweet sorghum bagasse (SSB) was achieved via the open simultaneous saccharification and fermentation (SSF) of L-lactic acid. To simplify the pretreatment process and reduce water consumption, a combined hydrolysis approach was applied and the NaOH-pretreated liquor (SL) was utilized as a partial neutralizing agent. In order to further enhance the product titer, the acid hydrolysate of SSJ (SSJAH) was fed, and MgO was used as a neutralizing agent. A product titer of 94 g L⁻¹ was obtained with a productivity of 1.55 g L⁻¹ h⁻¹, and the yield reached 98.31%. Totally, 274.79 g L-lactic acid was produced from 1 kg sweet sorghum stalk, and 83.22% water was saved compared with the previous study based on alkali pretreatment of SSB. This study provides an effective process for L-lactic acid biosynthesis from lignocellulosic substrates.