Polymethoxyflavones(PMFs)are a type of uncommon dietary flavonoids,characterized by more than one methoxy group,which exist in limited plant species,like Citrus species and Kaempferia parviflora.In addition,different ...Polymethoxyflavones(PMFs)are a type of uncommon dietary flavonoids,characterized by more than one methoxy group,which exist in limited plant species,like Citrus species and Kaempferia parviflora.In addition,different PMFs,such as nobiletin,sinensetin,tangeretin,and casticin,have been isolated from these natural sources.PMFs have received increasing attention due to their multiple bioactivities,such as antioxidant,anti-inflammatory,anti-cancer,metabolic regulatory,immunoregulatory,neuroprotective,and skin protective effects.These bioactivities of PMFs should be associated with the regulation of critical molecular targets and the interaction with gut microbiota.In order to provide a comprehensive and updated review of PMFs,their natural sources,refined extraction,biosynthesis,metabolism,and bioactivities are summarised and discussed,with the emphasis on the molecular mechanisms of PMFs on regulating different chronic diseases.Overall,PMFs may be promising flavonoids to the forefront of nutraceuticals for the prevention and/or treatment of certain human chronic diseases.展开更多
Carbazomycins(1-8)are a subgroup of carbazole derivatives that contain oxygen at the C3 and C4 positions and an unusual asymmetric substitution pattern.Several of these compounds exhibit antifungal and antioxidant act...Carbazomycins(1-8)are a subgroup of carbazole derivatives that contain oxygen at the C3 and C4 positions and an unusual asymmetric substitution pattern.Several of these compounds exhibit antifungal and antioxidant activities.To date,no systematic biosynthetic studies have been conducted on carbazomycins.In this study,carbazomycins A and B(1 and 2)were isolated from Streptomyces luteosporeus NRRL 2401 using a one-strain-many-compound(OSMAC)-guided natural product mining screen.A biosynthetic gene cluster(BGC)was iden-tified,and possible biosynthetic pathways for 1 and 2 were proposed.The in vivo genetic manipulation of the O-methyltransferase-encoding gene cbzMT proved indispensable for 1 and 2 biosynthesis.Size exclusion chro-matography indicated that CbzMT was active as a dimer.In vitro biochemical assays confirmed that CbzMT could repeatedly act on the hydroxyl groups at C3 and C4,producing monomethylated 2 and dimethylated 1.Monomethylated carbazomycin B(2)is not easily methylated;however,CbzMT seemingly prefers the dimethy-lation of the dihydroxyl substrate(12)to 1,even with a low conversion efficiency.These findings not only improve the understanding of carbazomycin biosynthesis but also expand the inventory of OMT-catalyzing it-erative methylations on different acceptor sites,paving the way for engineering biocatalysts to synthesize new active carbazomycin derivatives.展开更多
基金supported by the Local Financial Funds of National Agricultural Science and Technology Center,Chengdu,China(NASC2021KR01)the Agricultural Science and Technology Innovation Program(ASTIP-IUA-2022002)。
文摘Polymethoxyflavones(PMFs)are a type of uncommon dietary flavonoids,characterized by more than one methoxy group,which exist in limited plant species,like Citrus species and Kaempferia parviflora.In addition,different PMFs,such as nobiletin,sinensetin,tangeretin,and casticin,have been isolated from these natural sources.PMFs have received increasing attention due to their multiple bioactivities,such as antioxidant,anti-inflammatory,anti-cancer,metabolic regulatory,immunoregulatory,neuroprotective,and skin protective effects.These bioactivities of PMFs should be associated with the regulation of critical molecular targets and the interaction with gut microbiota.In order to provide a comprehensive and updated review of PMFs,their natural sources,refined extraction,biosynthesis,metabolism,and bioactivities are summarised and discussed,with the emphasis on the molecular mechanisms of PMFs on regulating different chronic diseases.Overall,PMFs may be promising flavonoids to the forefront of nutraceuticals for the prevention and/or treatment of certain human chronic diseases.
基金supported by a grant from the National Key research and development Program of China (2021YFA0909500,2021YFC2100100)National Natural Science Foundation of China (32170077,32170075).
文摘Carbazomycins(1-8)are a subgroup of carbazole derivatives that contain oxygen at the C3 and C4 positions and an unusual asymmetric substitution pattern.Several of these compounds exhibit antifungal and antioxidant activities.To date,no systematic biosynthetic studies have been conducted on carbazomycins.In this study,carbazomycins A and B(1 and 2)were isolated from Streptomyces luteosporeus NRRL 2401 using a one-strain-many-compound(OSMAC)-guided natural product mining screen.A biosynthetic gene cluster(BGC)was iden-tified,and possible biosynthetic pathways for 1 and 2 were proposed.The in vivo genetic manipulation of the O-methyltransferase-encoding gene cbzMT proved indispensable for 1 and 2 biosynthesis.Size exclusion chro-matography indicated that CbzMT was active as a dimer.In vitro biochemical assays confirmed that CbzMT could repeatedly act on the hydroxyl groups at C3 and C4,producing monomethylated 2 and dimethylated 1.Monomethylated carbazomycin B(2)is not easily methylated;however,CbzMT seemingly prefers the dimethy-lation of the dihydroxyl substrate(12)to 1,even with a low conversion efficiency.These findings not only improve the understanding of carbazomycin biosynthesis but also expand the inventory of OMT-catalyzing it-erative methylations on different acceptor sites,paving the way for engineering biocatalysts to synthesize new active carbazomycin derivatives.
