tetano
Editor, Senior Moderator
Bioorg Med Chem Lett. 2018 Jul 18. pii: S0960-894X(18)30610-3. doi: 10.1016/j.bmcl.2018.07.029. [Epub ahead of print]
[h=1]Generation of methylated violapyrones with improved anti-influenza A virus activity by heterologous expression of a type III PKS gene in a marine Streptomyces strain.[/h] Hou L[SUP]1[/SUP], Wang S[SUP]1[/SUP], Huang H[SUP]1[/SUP], Li H[SUP]2[/SUP], Wang W[SUP]3[/SUP], Li W[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Heterologous expression of the type III polyketide synthase (PKS) gene vioA in marine-derived Streptomyces youssoufiensis OUC6819 led to production of six violapyrones (VLPs), including four novel compounds VLPs Q-T (1-4) and two known compounds VLPs B and I (5 and 6). The structures of 1-4 were elucidated by a combination of spectroscopic analyses, including HR-ESIMS and 1D and 2D NMR data, demonstrating that 1-4 are novel VLPs which are methylated at 4-OH with their corresponding non-methylated counterparts to be VLP A, 5 and 6 and VLP C, respectively. Anti-influenza A [H1N1 (A/Virginia/ATCC1/2009) and H3N2 (A/Aichi/2/1968)] virus activity of compounds 1-6 as well as VLPs A and C were then evaluated using ribavirin as a positive control (IC[SUB]50[/SUB] = 66.7 and 99.6 μM). The results revealed that these VLPs showed considerable anti-H1N1 and anti-H3N2 activities with IC[SUB]50[/SUB] values of 30.6-132.4 μM and 45.3-150.0 μM, respectively. Notably, all the methylated VLPs displayed better anti-virus activity than their non-methylated counterparts, among which compound 3 (VLP S) exhibited the best activities. Interestingly, methylation at 4-OH has negative effect on the anti-MRSA (methicillin-resistant Staphylococcus aureus) activity instead, with methylated VLPs displaying decreased (2) or abolished (3 and 4) activities in comparison with each of their non-methylated counterparts.
[h=4]KEYWORDS:[/h] Anti-MRSA; Anti-influenza A; Heterologous expression; Streptomyces; Violapyrones (VLPs)
PMID: 30033162 DOI: 10.1016/j.bmcl.2018.07.029
[h=1]Generation of methylated violapyrones with improved anti-influenza A virus activity by heterologous expression of a type III PKS gene in a marine Streptomyces strain.[/h] Hou L[SUP]1[/SUP], Wang S[SUP]1[/SUP], Huang H[SUP]1[/SUP], Li H[SUP]2[/SUP], Wang W[SUP]3[/SUP], Li W[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Heterologous expression of the type III polyketide synthase (PKS) gene vioA in marine-derived Streptomyces youssoufiensis OUC6819 led to production of six violapyrones (VLPs), including four novel compounds VLPs Q-T (1-4) and two known compounds VLPs B and I (5 and 6). The structures of 1-4 were elucidated by a combination of spectroscopic analyses, including HR-ESIMS and 1D and 2D NMR data, demonstrating that 1-4 are novel VLPs which are methylated at 4-OH with their corresponding non-methylated counterparts to be VLP A, 5 and 6 and VLP C, respectively. Anti-influenza A [H1N1 (A/Virginia/ATCC1/2009) and H3N2 (A/Aichi/2/1968)] virus activity of compounds 1-6 as well as VLPs A and C were then evaluated using ribavirin as a positive control (IC[SUB]50[/SUB] = 66.7 and 99.6 μM). The results revealed that these VLPs showed considerable anti-H1N1 and anti-H3N2 activities with IC[SUB]50[/SUB] values of 30.6-132.4 μM and 45.3-150.0 μM, respectively. Notably, all the methylated VLPs displayed better anti-virus activity than their non-methylated counterparts, among which compound 3 (VLP S) exhibited the best activities. Interestingly, methylation at 4-OH has negative effect on the anti-MRSA (methicillin-resistant Staphylococcus aureus) activity instead, with methylated VLPs displaying decreased (2) or abolished (3 and 4) activities in comparison with each of their non-methylated counterparts.
[h=4]KEYWORDS:[/h] Anti-MRSA; Anti-influenza A; Heterologous expression; Streptomyces; Violapyrones (VLPs)
PMID: 30033162 DOI: 10.1016/j.bmcl.2018.07.029