Characterization of the depsidone gene cluster reveals etherification,decarboxylation and multiple halogenations as tailoring steps in depsidone assembly

Depsides and depsidones have attracted attention for biosynthetic studies due to their broad biological activities and structural diversity.Previous structure-activity relationships indicated that triple halogenated depsidones display the best anti-pathogenic activity.However,the gene cluster and the tailoring steps responsible for halogenated depsidone nornidulin(3)remain enigmatic.In this study,we disclosed the complete biosynthetic pathway of the halogenated depsidone through in vivo gene disruption,heterologous expression and in vitro biochemical experiments.We demonstrated an unusual depside skeleton biosynthesis process mediated by both highly-reducing polyketide synthase and nonreducing polyketide synthase,which is distinct from the common depside skeleton biosynthesis.This skeleton was subsequently modified by two in-cluster enzymes DepG and DepF for the ether bond formation and decarboxylation,respectively.In addition,the decarboxylase DepF exhibited substrate promiscuity for different scaffold substrates.Finally,and interestingly,we discovered a halogenase encoded remotely from the biosynthetic gene cluster,which catalyzes triple-halogenation to produce the active end product nornidulin(3).These discoveries provide new insights for further understanding the biosynthesis of depsidones and their derivatives.

New antibacterial depsidones from an ant-derived fungus Spiromastix sp.MY-1

Six new(1–6)and seven known depsidones(7–13)were isolated from the culture of an ant(Monomorium chinensis)-derived fungus Spiromastix sp.MY-1.Their structures were elucidated by extensive spectroscopic analysis including high resolution MS,1D and 2D NMR data.The new bromide depsidones were obtained through supplementing potassium bromide in the fermentation medium of Spiromastix sp.MY-1.All isolated compounds showed various bioactivities against the tested phytopathogenic bacteria.Particularly,new bromide compound 4,named spiromastixone S,exhibited the strongest activity against Xanthomonas oryzae pv.oryzae with a MIC value of 5.2μmol·^L(−1).

Lethaclado acid A and B from Lethariella cladonioides

Two new compounds, lethaclado acid A （1） and B （2）, were isolated from the acetone extract ofLethariella cladonioides. Their structures were elucidated on the basis of 1D and 2D NMR as well as ESI-MS spectral data.

Polyketides with potential bioactivities from the mangrove‑derived fungus Talaromyces sp.WHUF0362

Metabolites of microorganisms have long been considered as potential sources for drug discovery.In this study,fve new depsidone derivatives,talaronins A-E(1-5)and three new xanthone derivatives,talaronins F-H(6-8),together with 16 known compounds(9-24),were isolated from the ethyl acetate extract of the mangrove-derived fungus Talaromyces species WHUF0362.The structures were elucidated by analysis of spectroscopic data and chemical methods including alkaline hydrolysis and Mosher’s method.Compounds 1 and 2 each attached a dimethyl acetal group at the aromatic ring.A putative biogenetic relationship of the isolated metabolites was presented and suggested that the depsidones and the xanthones probably had the same biosynthetic precursors such as chrysophanol or rheochrysidin.The antimicrobial activity assay indicated that compounds 5,9,10,and 14 showed potent activity against Helicobacter pylori with minimum inhibitory concentration(MIC)values in the range of 2.42-36.04μmol/L.While secalonic acid D(19)demonstrated signifcant antimicrobial activity against four strains of H.pylori with MIC values in the range of 0.20 to 1.57μmol/L.Furthermore,secalonic acid D(19)exhibited cytotoxicity against cancer cell lines Bel-7402 and HCT-116 with IC_(50) values of 0.15 and 0.19μmol/L,respectively.The structure–activity relationship of depsidone derivatives revealed that the presence of the lactone ring and the hydroxyl at C-10 was crucial to the antimicrobial activity against H.pylori.The depsidone derivatives are promising leads to inhibit H.pylori and provide an avenue for further development of novel antibiotics.