Scripps Florida Logo

Shen Lab Research: Project 3

(iii) Engineering of natural product structure diversity by combinatorial biosynthesis methods for drug discovery and development

1. Engineered production of C-1027 analogs and evaluation of the analogs as anticancer drug (Science 2002, 297, 1170-1173; Cancer Res. 2007, 67, 773-781; Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 17632-17637; Cancer Res. 2009, 69, 593-598)

Diagram of C-1027 analogs

2. Engineered overproduction of fredericamycin A and E by manipulation of pathway regulation (J. Bacteriol. 2008, 190, 5587-5596)

Diagram of  fredericamycin A and E

3. Evaluation of migrastatin, dorrigocin, and congeners as tumor cell migration inhibitors (Bioorg. Med. Chem. Lett. 2008, 18, 5951-5954)

Diagram of migrastatin, dorrigocin, and congeners

4. Engineered production of decarbamoyl bleomycins (J. Biol. Chem. 2008, 283, 28236-28245)

Diagram of decarbamoyl bleomycins

5. Evaluation of iso-migrastatin, lactimidomycin, and congeners as tumor cell migration inhibitors (J. Am. Chem. Soc. 2009, 131, 1370-1371)

Diagram of iso-migrastatin, lactimidomycin, and congeners

6. Engineered overproduction of platensimycin and platencin by manipulation of pathway regulation (Antimicrob. Agents Chermother. 2009, 53, 1299-1304)

Diagram of platensimycin and platencin

7. Engineered production of tallysomycin analogues (J. Biol. Chem. 2009, 284, 8256-8264)

Diagram of tallysomycin analogues

8. Engineered production of tautomycin analogues (Org. Lett. 2009, 11, 1639-1642)

Diagram of tautomycin analogues

9. Evaluation of tautomycin and tautomycetin as drug leads for neuroendocrine cancers (Mol. Cancer Therap. 2009, 8, 914-920; Am. J. Surg. 2009, 197, 313-319)

Diagram of tautomycin and tautomycetin

10. Engineered production of fredericamycin analogues (J. Biol. Chem. 2009, 284, 24735-24743)

Diagram of fredericamycin analogues

11. Engineered production of tallysomycin analogues (Mol. BioSyst. 2010, 6, 349-356; Appl. Microbiol. Biotechnol. 2010, 86, 1345-1353)

Diagram of tallysomycin analogues

12. Evaluation of the glutarimide-containing polyketide library resulting in the discovery of inhibition of eukaryotic translation elongation as a mode of action (Nat. Chem. Biol. 2010, 6, 209-217)

Diagram of glutarimide-containing polyketide

13. Engineered overproduction of platencin and analogues by manipulation of pathway regulation (Org. Lett. 2010, 12, 1744-1747)

Diagram of platencin and analogues

14. Engineered overproduction of tautomycetin analogues by (J. Am. Chem. Soc. 2010, 132, 6663-6671)

Digram of tautomycetin analogues

15. Engineered overproduction of C-1027 and analogues by manipulation of pathway regulation (J. Antibiot. 2010, 63, 482-485; J. Nat. Prod. 2011, 74, in press)

Diagram of C-1027 and analogues

16. Engineered production of leinamycin analogues (Org. Lett. 2011, 13, 498-501)

Diagram of leinamycin analogues

17. Evaluation of the tautomycin and tautomycetin library resulting in the discovery of SHP2 as a target (Nat. Chem. Biol. 2010, 6, 209-217)

Diagram of  tautomycin and tautomycetin