Bacterial UDP-Glucose Hydrolases and P2 Receptor-Mediated Responses to Infection: A Commentary

UDP-glucose hydrolases are a group of relatively little known membrane-bound or periplasmic enzymes found in Salmonella enterica and E. coli. UDP-glucose is an agonist for a specific P2 receptor (P2Y14) found on epithelial cells and cells associated with innate immunity. It is also recognised as a ‘danger signal’. Cells respond to mechanical damage by releasing UDP-glucose which activates P2Y14 to trigger an innate immune response;it is postulated that a similar response to bacterial infection may be protective against infection. However, the UDP-glucose hydrolases may constitute virulence factors able to abrogate this response by degradation of the released UDP-glucose.

UDP-glucose epimerase 1,moonlighting as a transcriptional activator,is essential for tapetum degradation and male fertility in rice

Multiple enzymes perform moonlighting functions distinct from their main roles.UDP-glucose epimerases(UGEs),a subclass of isomerases,catalyze the interconversion of UDP-glucose(UDP-Glc)and UDP-galactose(UDP-Gal).We identified a rice male-sterile mutant,osuge1,with delayed tapetum degradation and abortive pollen.The mutant osuge1 protein lacked UDP-glucose epimerase activity,resulting in higher UDP-Gal content and lower UDP-Glc levels in the osuge1 mutant compared with the wild type.Interestingly,we discovered that OsUGE1 participates in the TIP2/bHLH142–TDR–EAT1/DTD transcriptional regulatory cascade involved in tapetum degradation,in which TIP2 and TDR regulate the expression of OsUGE1 while OsUGE1 regulates the expression of EAT1.In addition,we found that OsUGE1 regulates the expression of its own gene by directly binding to an E-box element in the OsUGE1 promoter.Collectively,our results indicate that OsUGE1 not only functions as a UDP-glucose epimerase but also moonlights as a transcriptional activator to promote tapetum degradation,revealing a novel regulatory mechanism of rice reproductive development.

Systematic optimization of the yeast cell factory for sustainable and high efficiency production of bioactive ginsenoside compound K

Ginsenoside Compound K(CK)has been recognized as a major functional component that is absorbed into the systemic circulation after oral administration of ginseng.CK demonstrates diverse bioactivities.A phase I clinical study indicated that CK was a potential candidate for arthritis therapy.However,a phase II clinical study was suspended because of the high cost associated with the present CK manufacturing approach,which is based on the traditional planting-extracting-biotransforming process.We previously elucidated the complete CK biosynthetic pathway and realized for the first time de novo biosynthesis of CK from glucose by engineered yeast.However,CK production was not sufficient for industrial application.Here,we systematically engineered Saccharomyces cerevisiae to achieve high titer production of CK from glucose using a previously constructed protopanaxadiol(PPD)-producing chassis,optimizing UGTPg1 expression,improving UDP-glucose biosynthesis,and tuning down UDP-glucose consumption.Our final engineered yeast strain produced CK with a titer of 5.74 g/L in fed-batch fermentation,which represents the highest CK production in microbes reported to date.Once scaled-up,this high titer de novo microbial biosynthesis platform will enable a robust and stable supply of CK,thus facilitating study and medical application of CK.