Lactic acid (LA) is an important platform chemical due to its significant applications in various fields and its use as a monomer for the production of biodegradable poly(lactic acid) (PLA). Free LA ...production is required to get rid of CaSO
4
, a waste material produced during fermentation at neutral pH which will lead to easy purification of LA required for the production of biodegradable PLA. Additionally, there is no need to use corrosive acids to release free LA from the calcium lactate produced during neutral fermentation. To date, several attempts have been made to improve the acid tolerance of lactic acid bacteria (LAB) by using both genome-shuffling approaches and rational design based on known mechanisms of LA tolerance and gene deletion in yeast strains. However, the lack of knowledge and the complexity of acid-tolerance mechanisms have made it challenging to generate LA-tolerant strains by simply modifying few target genes. Currently, adaptive evolution has proven an efficient strategy to improve the LA tolerance of individual/engineered strains. The main objectives of this article are to summarize the conventional biotechnological LA fermentation processes to date, assess their overall economic and environmental cost, and to introduce modern LA fermentation strategies for free LA production. In this review, we provide a broad overview of free LA fermentation processes using robust LAB that can ferment in acidic environments, the obstacles to these processes and their possible solutions, and the impact on future development of free LA fermentation processes commercially.
Traditional fermented foods are a significant source of starter and/or non‐starter lactic acid bacteria (nsLAB). Moreover, these microorganisms are also known for their role as probiotics. The ...potential of nsLAB is huge; however, there are still challenges to be overcome with respect to characterization and application. In the present review, the most important steps that autochthonous lactic acid bacteria isolated from fermented foods need to overcome, to qualify as novel starter cultures, or as probiotics, in food technology and biotechnology, are considered. These different characterization steps include precise identification, detection of health‐promoting properties, and safety evaluation. Each of these features is strain specific and needs to be accurately determined. This review highlights the advantages and disadvantages of nsLAB, isolated from traditional fermented foods, discussing safety aspects and sensory impact.
High chiral purity of lactic acid is a crucial indicator for the synthesis of chiral lactide as the primary intermediate chemical for ring‐open polymerization of high molecular weight polylactic acid ...(PLA). Lignocellulose biomass is the most promising carbohydrate feedstock for commercial production of PLA, but the presence of trace d‐lactic acid in the biorefinery chain adversely affects the synthesis and quality of chiral lactide. This study analyzed the fingerprint of trace
d‐lactic acid in the biorefinery chain and found that the major source of
d‐lactic acid comes from lignocellulose feedstock. The naturally occurring lactic acid bacteria and water‐soluble carbohydrates in lignocellulose feedstock provide the necessary conditions for
d‐lactic acid generation. Three strategies were proposed to eliminate the generation pathway of
d‐lactic acid, including reduction of moisture content, conversion of water‐soluble carbohydrates to furan aldehydes in pretreatment, and conversion to
l‐lactic acid by inoculating engineered
l‐lactic acid bacteria. The natural reduction of lactic acid content in lignocellulose feedstock during storage was observed due to the lactate oxidase‐catalyzed oxidation of
l‐ and
d‐lactic acids. This study provided an important support for the production of cellulosic
l‐lactic acid with high chiral purity.
Trace d‐lactic acid fingerprint was identified in the biorefinery processing chain, then lignocellulose feedstock was the primary source of
d‐lactic acid generation due to the existence of occurring lactic acid bacteria and water‐soluble carbohydrates. Three strategies were proposed and tested to eliminate the trace
d‐lactic acid generation in the biorefinery chain. This study provides strong technical support for the production of high chiral purity
l‐lactic acid from lignocellulose feedstocks.
The purpose of the present work was to gain a fundamental understanding of how the composition and physico-chemical properties affect the rheology, morphology, miscibility, and thermal stability of ...poly(lactic acid) (PLA)-poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) biopolymer blends obtained by melt mixing. First, restricted processing conditions were chosen, due to the inherent thermal degradation of PHBV, as proven by rheological dynamic time sweep (DTS) measurements and size-exclusion chromatography (SEC). Based on this, the composition dependence of the blends was investigated using small-amplitude oscillatory shear rheology (SAOS), and the results were confirmed by scanning electron microscopy (SEM) analysis. Subsequently, the changes in glass transition temperatures (Tsub.gs) from the molten to the solid state, as observed by DMA and DSC, were verified by coupling SAOS to dielectric relaxation spectroscopy (DRS). Herein, the thermo-rheological complexity of PLA/PHBV blends in the melt was revealed, especially for PLA-rich blends. Irregularly structured morphologies, caused by highly mismatched viscoelastic properties, illustrated the degree of partial miscibility. Moreover, the thermo-rheological complexity appeared in the molten state of the asymmetric PLA-rich phases could be correlated to the crystal-amorphous interfacial MWS polarization, because of the locally-induced phase separation and heterogeneity, and owing to the differences in their crystallization properties during cooling. The miscibility also suffered from the lower thermal stability of PLA and the even more unstable PHBV. Nevertheless, the melt-induced degradation process of the PLA/PHBV blends seemed to be responsible for some of the in situ self-compatibilization and plasticization mechanisms. As a result, the miscibility and thermo-rheological simplicity were improved for the intermediate and PHBV-rich compositions at low temperatures, since their properties were, to a large extent, governed by the significant degradation of PHBV. The present findings should increase the understanding of morphological changes in PLA/PHBV blends and help control their micro/nanostructure.
The development and implementation of renewable materials for the production of versatile chemical resources have gained considerable attention recently, as this offers an alternative to the ...environmental problems caused by the petroleum industry and the limited supply of fossil resources. Therefore, the concept of utilizing biomass or wastes from agricultural and industrial residues to produce useful chemical products has been widely accepted. Lactic acid plays an important role due to its versatile application in the food, medical, and cosmetics industries and as a potential raw material for the manufacture of biodegradable plastics. Currently, the fermentative production of optically pure lactic acid has increased because of the prospects of environmental friendliness and cost-effectiveness. In order to produce lactic acid with high yield and optical purity, many studies focus on wild microorganisms and metabolically engineered strains. This article reviews the most recent advances in the biotechnological production of lactic acid mainly by lactic acid bacteria, and discusses the feasibility and potential of various processes.
The balance of programmed death-1 (PD-1)-expressing CD8+ T cells and regulatory T (Treg) cells in the tumor microenvironment (TME) determines the clinical efficacy of PD-1 blockade therapy through ...the competition of their reactivation. However, factors that determine this balance remain unknown. Here, we show that Treg cells gain higher PD-1 expression than effector T cells in highly glycolytic tumors, including MYC-amplified tumors and liver tumors. Under low-glucose environments via glucose consumption by tumor cells, Treg cells actively absorbed lactic acid (LA) through monocarboxylate transporter 1 (MCT1), promoting NFAT1 translocation into the nucleus, thereby enhancing the expression of PD-1, whereas PD-1 expression by effector T cells was dampened. PD-1 blockade invigorated the PD-1-expressing Treg cells, resulting in treatment failure. We propose that LA in the highly glycolytic TME is an active checkpoint for the function of Treg cells in the TME via upregulation of PD-1 expression.
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•LA induces PD-1 expression by Treg cells in highly glycolytic tumors•LA absorbed through MCT1 is a metabolic checkpoint of immune responses•MYC-amplified or liver metastatic tumors augment PD-1+ Treg cells with abundant LA•MCT1 highly expressed by Treg cells provides therapeutic target for immunotherapy
Kumagai et al. show that Treg cells uptake lactic acid in the highly glycolytic tumor microenvironment via MCT1 and robustly express PD-1, resulting in the impairment of PD-1 blockade therapy.
The quality of the monomers lactic acid and lactide as well as the chemical changes induced during polymerization and processing are crucial parameters for controlling the properties of the resulting ...poly(lactic acid) (PLA) products. This review presents the most important analysis and characterization methods for quality assessment of PLA and its precursors. The impurities typically present in lactic acid or lactide monomers and their possible origins and effects on resulting PLA products are discussed. The significance of the analyses for the different polymer production stages is considered, and special applications of the methods for studying features specific for PLA-based materials are highlighted.