Halichondrin B

Biosynthesis

While a producer organism for Halichondrin B has never been isolated in pure culture, the structural features of Halichondrin B, such as the 'odd-even' rule of methylation, and the abundance of oxygen heterocycles, suggest it is a product of dinoflagellate polyether metabolism In support of this conjecture, the known dinoflagellate toxin okadaic acid was isolated from the same species of sponge. But, halichondrin B is not found in the geographically and relatively phylogenetically close sponges H. panicea or H. japonica which are found in similar tide pools in Japan as Halichondria okadai. In constrast, halichondrins have been reported from geographically and phylogenetically distant sponges to Halichondria okadai, including Axinella sp. and Phakellia carteri, and Lissodendoryx. Aquaculture of the New Zealand sponge Lissodendoryx n. sp. 1 over at least 7 years, distant from its original range (at ~10 m depth nearby Wellington vs its native range ~90 m deep off the Kaikōura Peninsula), established it could produce halichondrin B at a relatively high yield over a timecourse of years, suggesting that halichondrins were being produced by vertically inherited symbionts, rather than being concentrated from a dietary source present in the environment.{{cite book | last1=Hart | first1=Joanne B. | last2=Lill | first2=Rachel E. | last3=Hickford | first3=Sarah J.H. | last4=Blunt | first4=John W. | last5=Munro | first5=Murray H.G.

References

References

1. (1986). "Halichondrins - antitumor polyether macrolides from a marine sponge". Pure Appl. Chem..
2. "Success Story: Halichondrin B (NSC 609395) E7389 (NSC 707389)". Developmental Therapeutics Program, [[National Cancer Institute]].
3. "NCI-60 DTP Human Tumor Cell Line Screen". Developmental Therapeutics Program, National Cancer Institute.
4. (August 1991). "Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data". J. Biol. Chem..
5. (1992). "Total synthesis of halichondrin B and norhalichondrin B". J. Am. Chem. Soc..
6. (February 2001). "In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B". Cancer Res..
7. (2005). "Anticancer agents from natural products". Taylor & Francis.
8. (2010-11-15). "FDA approves new treatment option for late-stage breast cancer". USFDA.
9. Kawano, Satoshi. (2019-06-17). "A landmark in drug discovery based on complex natural product synthesis". Scientific Reports.
10. Kaburagi, Yosuke. (2024-04-12). "Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials". Organic Letters.
11. Sasaki, Takeo. (2024-06-21). "What Does It Take to Develop Structurally Complex Molecules by Total Synthesis? Rapid Process Development and GMP Manufacturing of E7130 Drug Substance for First-in-Human Clinical Study". Organic Process Research & Development.
12. (2014-06-16). "Polyketide biosynthesis in dinoflagellates: what makes it different?". Royal Society of Chemistry (RSC).
13. (1981). "Okadaic acid, a cytotoxic polyether from two marine sponges of the genus Halichondria". American Chemical Society (ACS).
14. Abe, Takahiro. (2012-04-23). "Construction of a Metagenomic Library for the Marine Sponge Halichondria okadai". Bioscience, Biotechnology, and Biochemistry.
15. Pettit, George R.. (1991). "Antineoplastic agents. 219. Isolation and structure of the cell growth inhibitory constituents from the western Pacific marine sponge Axinella sp". Journal of Medicinal Chemistry.
16. Pettit, George R.. (1993). ": Isolation and structure of halistatin 1 from the eastern Indian Ocean marine sponge Phakellia carteri". The Journal of Organic Chemistry.
17. Munro, Murray H.G.. (1999). "The discovery and development of marine compounds with pharmaceutical potential". Journal of Biotechnology.
18. (2009). "Therapeutic agents from the sea: biodiversity, chemo-evolutionary insight and advances to the end of Darwin’s 200th year". South Pacific Underwater Medicine Society (Incorporated in Victoria) AO020660B and the European Underwater and Baromedical Society.