Abstract
Syringolin, synthesized by a mixed non-ribosomal peptide synthetase/polyketide synthetase in Pseudomonas syringae pv. syringae (Pss) B728a, is a novel eukaryotic proteasome inhibitor. Meanwhile, directly modifying large fragments in the PKS/NRPS gene cluster through traditional DNA engineering techniques is very difficult. In this study, we directly cloned the syl gene cluster from Pss B301D-R via Red/ET recombineering to effectively express syringolin in heterologous hosts. A 22 kb genomic fragment containing the sylA-sylE gene cluster was cloned into the pASK vector, and the obtained recombinant plasmid was transferred into Streptomyces coelicolor and Streptomyces lividans for the heterologous expression of syringolin. Transcriptional levels of recombinant syl gene in S. coelicolor M145 and S. lividans TK24 were evaluated via RT-PCR and the production of syringolin compounds was detected via LC-MS analysis. The extracts of the engineered bacteria showed cytotoxic activity to B16, 4T1, Meth-A, and HeLa tumor cells. It is noteworthy that the syringolin displayed anticancer activity against C57BL/6 mice with B16 murine melanoma tumor cells. Together, our results herein demonstrate the potential of syrinolin as effective antitumo...Continue Reading
References
May 1, 1994·The Journal of Antibiotics·S ChatterjeeL Vertesy
Feb 26, 1999·Nucleic Acids Research·J P MuyrersA F Stewart
Dec 2, 2000·Nature Biotechnology·Y ZhangA F Stewart
May 10, 2001·Trends in Biochemical Sciences·J P MuyrersA F Stewart
Apr 18, 2002·Leukemia·J B Almond, G M Cohen
Jan 13, 2004·Molecular Plant-microbe Interactions : MPMI·Hans AmreinRobert Dudler
Nov 1, 2005·Metabolic Engineering·Luke Z YuanWonchul Suh
Nov 18, 2006·Cell Proliferation·C S ColemanA S Bachmann
Feb 24, 2007·Chemical Reviews·Ljudmila Borissenko, Michael Groll
Apr 11, 2008·Nature·Michael GrollRobert Dudler
Aug 15, 2008·Nucleic Acids Research·Jun FuYouming Zhang
Dec 19, 2008·Chembiochem : a European Journal of Chemical Biology·Sabine GrüschowRebecca J M Goss
Apr 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jérôme ClercMarkus Kaiser
Apr 11, 2009·Chembiochem : a European Journal of Chemical Biology·Thilo WaltherHans-Dieter Arndt
Dec 9, 2009·Journal of the American Chemical Society·Heidi J ImkerWilliam M Wuest
Jan 25, 2011·Cancer Letters·Thomas C ChenAxel H Schönthal
Jul 19, 2011·Proteome Science·Yushuang LuoYunjun Sun
Aug 5, 2011·Organic Letters·William M WuestChristopher T Walsh
May 1, 2012·Nature Biotechnology·Jun FuYouming Zhang
Aug 3, 2012·Molecular Plant-microbe Interactions : MPMI·Christina RamelRobert Dudler
Aug 28, 2012·Applied and Environmental Microbiology·Yunlei ZhangFeng Wu
Aug 16, 2013·Molecular Plant-microbe Interactions : MPMI·Silvia Schelbert HofstetterRobert Dudler
Apr 29, 2016·Organic Letters·Shun KitahataSatoshi Ichikawa
Jul 5, 2016·Chemical & Pharmaceutical Bulletin·Takuya ChibaSatoshi Ichikawa
Sep 20, 2016·Bioorganic & Medicinal Chemistry Letters·Henrik HarmsRoger G Linington
Jun 15, 2017·Annual Review of Phytopathology·Joel L Vanneste
Citations
Jan 9, 2019·Natural Product Reports·Liujie HuoRolf Müller
Mar 6, 2019·Microbial Biotechnology·Olga N SekurovaSergey B Zotchev
Aug 28, 2019·Natural Product Reports·Maksym Myronovskyi, Andriy Luzhetskyy
Jun 15, 2019·Natural Product Reports·Jia Jia ZhangBradley S Moore
Jan 15, 2021·Current Opinion in Biotechnology·Hahk-Soo Kang, Eung-Soo Kim
Jan 25, 2020·Trends in Biotechnology·Muhammad Nazeer AbbasiAiying Li
Jul 31, 2021·Frontiers in Bioengineering and Biotechnology·Wenfang WangYinhua Lu