Combinatorial Strategies by Marine Cyanobacteria: Symplostatin 4, an Antimitotic Natural Dolastatin 10/15 Hybrid that Synergizes with the Coproduced HDAC Inhibitor Largazole

Abstract

Combinatorial biosynthesis meets combinatorial pharmacology, cyanobacterial style: A new antimitotic natural product with features of both dolastatins 10 and 15 was isolated from the same Floridian Symploca sp. sample that produced the histone deacetylase inhibitor largazole. Both agents in combination are more effective in inhibiting cancer cell proliferation than either agent alone.