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About two-thirds of small molecule drugs contain methyl group and it plays a very important role in the drug development. So, methyltransferases catalyzing the methylation have always attracted great attention. Hangtaimycin (HTM) is a potent hepatoprotective agent. Previous study showed that its biosynthetic gene cluster contained three methyltransferase domains, but their characteristics in HTM biosynthetic pathway has not been revealed. In this study, we clarified multi-methylations in HTM biosynthesis in vivo. It showed that the two Sadenosylmethionine- dependent methyltransferases (SAM-MTs) of HtmA2(-module 6)-MT domain and HtmB2 (-module 18)-MT domain are responsible for the installation of methyl group at C-45 and N-12, respectively, whereas the FK506 methyltransferase (FKMT) type O-methyltransferase of HtmB1(-module 16)-MT domain take care of the methylation at O-21 of HTM. We also reported the antibacterial activities of HTM in this study, and found that it showed activities against M. luteus, B. thuringiensis and A. baumannii with MIC of 4 μg/mL, 4 μg/mL, and 64 μg/mL, respectively. [ABSTRACT FROM AUTHOR]

A new butoxy substituted indolediketopiperazine (1), together with five known indolediketopiperazines (2-6), which are derivatives of brevianamides, were isolated from the marine derived fungus Aspergillus sp. 66may. Careful analysis and comparison of the HRESIMS, as well as 1D and 2D NMR datasets, identified the structures of the isolated compounds. The subsequent antibacterial and anti-inflammatory activities showed that compound 4 possessed antimicrobial bioactivities against Bacillus subtilis ATCC 39620 with minimum inhibitory concentration (MIC) value of 64 µg/mL. Compounds 1, 2, 4 exhibited potential inhibitory activities against NO production with IC50 value of 28.2, 21.3, 23.6 µM, respectively. It seems that butoxy substitution at C-9 in brevianamides have little effects on their antimicrobial and anti-inflammatory bioactivities. [ABSTRACT FROM AUTHOR]