Combining semi-synthesis with plant and microbial biocatalysis: new frontiers in producing a chemical arsenal against cancer†

Authors

Samuel Gary, West Virginia University
Janet Adegboye, Ohio State University
Brian Popp, West Virginia University
Jean-Christophe Cocuron, Ohio State University
Brooklyn Woodrum, West Virginia University
Nik Kovinich, West Virginia UniversityFollow

Author ORCID Identifier

N/A

N/A

https://orcid.org/0000-0001-6367-1168

N/A

N/A

https://orcid.org/0000-0002-9396-6626

Document Type

Article

Publication Date

2018

College/Unit

Davis College of Agriculture, Natural Resources and Design

Department/Program/Center

Division of Plant and Soil Sciences

Abstract

Natural products (NPs) that exhibit anticancer activities are frequently not potent enough to be used clinically as therapeutics. Semi-synthesis and metabolic engineering are promising approaches for producing more efficacious derivatives of anticancer NPs (ACNPs), but each technique alone can be inefficient at obtaining specific ACNP derivatives that may be suspected to have enhanced anticancer activity. Here, we demonstrate that the methods of semi-synthesis and biocatalysis can be used as modules in succession and in different combinations to produce 6,8-dibromogenkwanin, a derivative of the ACNP apigenin. Further, we demonstrated that soybean seed coats can be used as a biocatalyst to convert brominated flavonoids into multiple derivatives. A strength of the combinatorial (bio)synthesis approach was that the order of the modules could be rearranged to increase the yield of the desired product. At lower treatment concentration (5 mM), 6,8-dibromogenkwanin exhibited enhanced antiproliferative activities against HT-29 colorectal adenocarcinoma cancer cells under normoxic and hypoxic conditions compared to its ACNP precursors, but not at higher concentrations. Dose–response analyses suggested that dibromogenkwanin had a distinct mode-of-action compared to apigenin. Thus, this proof-of-concept paper demonstrates combinatorial (bio)synthesis as an approach that can be used to produce novel chemistries for anticancer research.

Digital Commons Citation

Gary, Samuel; Adegboye, Janet; Popp, Brian; Cocuron, Jean-Christophe; Woodrum, Brooklyn; and Kovinich, Nik, "Combining semi-synthesis with plant and microbial biocatalysis: new frontiers in producing a chemical arsenal against cancer†" (2018). Faculty & Staff Scholarship. 1940.
https://researchrepository.wvu.edu/faculty_publications/1940

Source Citation

Gary, S., Adegboye, J., Popp, B., Cocuron, J.-C., Woodrum, B., & Kovinich, N. (2018). Combining semi-synthesis with plant and microbial biocatalysis: new frontiers in producing a chemical arsenal against cancer. RSC Advances, 8(38), 21332–21339. https://doi.org/10.1039/c8ra02184h