Peptidoglycan(PG),the essential exoskeleton in most bacteria,is synthesized through the action of bacterial transglycosylases(TGases),positioning these enzymes as elegant and desirable targets for antibiotic discovery...Peptidoglycan(PG),the essential exoskeleton in most bacteria,is synthesized through the action of bacterial transglycosylases(TGases),positioning these enzymes as elegant and desirable targets for antibiotic discovery.This review covers the major TGases involved in PG biogenesis,including TGases from the glycosyltransferase family 51(GT51)and the newly discovered shape,elongation,division,sporulation(SEDS)family.We discuss the distinct roles of these two TGases during PG synthesis and emphasize the structural and catalytic differences,highlighting their coordination in PG assembly.Moreover,we summarize recent advances in TGase-involved antimicrobial strategies,including substrate-mimicking TGase inhibitors,PG terminators,and TGase-related immunological therapy targeting TGase from the GT51 family,and the first non-substrate-like TGase inhibitor against the SEDS protein.These valuable insights pave the way for the further development of novel TGase-related antimicrobial agents.展开更多
Starch modification is vital for tailoring properties,involving changes in amylose/amylopectin ratio,chain lengths,and types of glucosidic linkages.Enzymatic modification,occurring on raw granular starch or postgelati...Starch modification is vital for tailoring properties,involving changes in amylose/amylopectin ratio,chain lengths,and types of glucosidic linkages.Enzymatic modification,occurring on raw granular starch or postgelatinization,offers mild,safe,and eco-friendly approaches.Although gelatinized starch allows more effi-cient modification,retaining the granular form is desirable for reduced energy consumption and hindering of retrogradation.Transglycosylases(TGases),such as branching enzyme,cyclodextrin glucanotransferase and 4-α-glucanotransferase,have gained attention for improving physiochemical attributes of starches by altering the structures of theα-glucan molecules.The TGases have been applied alone as well as in combination with chemical and/or physical treatments,manifesting the broad diversity in starch modification.However,under-standing the relationship between the structures of TGases and their reaction products from granular starch is lagging behind.The present mini review aims to provide and discuss:i)structural features of different TGases applied in granular starch modification;ii)effects of enzymatic modification of starch granules,including use of single or multiple enzymes;iii)obtained modifications from the perspective of enzyme structures having an open,a loop-blocked or a tunnel-shaped active site.展开更多
Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus(T2DM).Various acarbose analogs have been identified while exploring compounds with improved pharmacological ...Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus(T2DM).Various acarbose analogs have been identified while exploring compounds with improved pharmacological properties.In this study,we found that AcbE from Actinoplanes sp.SE50/110 catalyzes the production of acarbose analogs that exhibit significantly improved inhibitory activity towardsα-amylase than acarbose.Recombinant AcbE mainly catalyzed the formation of two new compounds,namely acarstatins A and B,using acarbose as substrate.Using high-resolution mass spectrometry,nuclear magnetic resonance,and glycosidase hydrolysis,we elucidated their chemical structures as O-α-d-maltosyl-(1→4)-acarbose and O-α-d-maltotriosyl-(1→4)-acarbose,respectively.Acarstatins A and B exhibited 1584-and 1478-fold greater inhibitory activity towards human salivaryα-amylase than acarbose.Furthermore,both acarstatins A and B exhibited complete resistance to microbiome-derived acarbose kinase 1-mediated phosphorylation and partial resistance to acarbose-preferred glucosidase-mediated hydrolysis.Therefore,acarstatins A and B have great potential as candidate therapeutic agents for T2DM.展开更多
基金supported by the Ministry of Education(MOE-T2EP30120-0007)the Nanyang Technological University,Singapore(RG107/23).
文摘Peptidoglycan(PG),the essential exoskeleton in most bacteria,is synthesized through the action of bacterial transglycosylases(TGases),positioning these enzymes as elegant and desirable targets for antibiotic discovery.This review covers the major TGases involved in PG biogenesis,including TGases from the glycosyltransferase family 51(GT51)and the newly discovered shape,elongation,division,sporulation(SEDS)family.We discuss the distinct roles of these two TGases during PG synthesis and emphasize the structural and catalytic differences,highlighting their coordination in PG assembly.Moreover,we summarize recent advances in TGase-involved antimicrobial strategies,including substrate-mimicking TGase inhibitors,PG terminators,and TGase-related immunological therapy targeting TGase from the GT51 family,and the first non-substrate-like TGase inhibitor against the SEDS protein.These valuable insights pave the way for the further development of novel TGase-related antimicrobial agents.
基金supported by the Independent Research Fund Denmark,project BioMarch,grant#3105-00327B(Birte Svensson,Andreas Blennow,and Dennis Sandris Nielsen)China Scholarship Council(CSC)grant#202006790033(Yu Wang)Technical Uni-versity of Denmark.
文摘Starch modification is vital for tailoring properties,involving changes in amylose/amylopectin ratio,chain lengths,and types of glucosidic linkages.Enzymatic modification,occurring on raw granular starch or postgelatinization,offers mild,safe,and eco-friendly approaches.Although gelatinized starch allows more effi-cient modification,retaining the granular form is desirable for reduced energy consumption and hindering of retrogradation.Transglycosylases(TGases),such as branching enzyme,cyclodextrin glucanotransferase and 4-α-glucanotransferase,have gained attention for improving physiochemical attributes of starches by altering the structures of theα-glucan molecules.The TGases have been applied alone as well as in combination with chemical and/or physical treatments,manifesting the broad diversity in starch modification.However,under-standing the relationship between the structures of TGases and their reaction products from granular starch is lagging behind.The present mini review aims to provide and discuss:i)structural features of different TGases applied in granular starch modification;ii)effects of enzymatic modification of starch granules,including use of single or multiple enzymes;iii)obtained modifications from the perspective of enzyme structures having an open,a loop-blocked or a tunnel-shaped active site.
基金This work was supported by the National Key Research and Development Program of China(grant No.2021YFC2100600)National Natural Science Foundation of China(grant No.31830104)Science and Technology Commission of Shanghai Municipality(grant Nos.19JC1413000 and 19430750600)to L.B.We thank the Core Facility and Technical Service Center for SLSB and the Instrumental Analysis Center in SJTU for data collection.
文摘Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus(T2DM).Various acarbose analogs have been identified while exploring compounds with improved pharmacological properties.In this study,we found that AcbE from Actinoplanes sp.SE50/110 catalyzes the production of acarbose analogs that exhibit significantly improved inhibitory activity towardsα-amylase than acarbose.Recombinant AcbE mainly catalyzed the formation of two new compounds,namely acarstatins A and B,using acarbose as substrate.Using high-resolution mass spectrometry,nuclear magnetic resonance,and glycosidase hydrolysis,we elucidated their chemical structures as O-α-d-maltosyl-(1→4)-acarbose and O-α-d-maltotriosyl-(1→4)-acarbose,respectively.Acarstatins A and B exhibited 1584-and 1478-fold greater inhibitory activity towards human salivaryα-amylase than acarbose.Furthermore,both acarstatins A and B exhibited complete resistance to microbiome-derived acarbose kinase 1-mediated phosphorylation and partial resistance to acarbose-preferred glucosidase-mediated hydrolysis.Therefore,acarstatins A and B have great potential as candidate therapeutic agents for T2DM.
