Freshwater is essential for drinking and agriculture, yet potable watersheds are increasingly impacted by the undesirable high-density growth of algae and/or cyanobacteria. Understanding, monitoring, and remediating harmful algal/cyanobacterial blooms (HABs/cyanoHABs) and their associated toxins are essential to reducing their societal impact. Recent scientific and technological advances continue to improve environmental cyanoHAB detection and prediction; however, the vast cyanotoxin structural chemodiversity creates challenges in their comprehensive detection and quantification using standard analytical chemistry assays. In contrast, quantitative molecular biological detection of biosynthetic genes via PCR provides a multiplexable and cost-effective monitoring strategy to identify the toxic potential of blooms independent of active toxin synthesis. The biosynthetic gene clusters (BGCs) for important freshwater cyanotoxins like microcystin, cylindrospermopsin, saxitoxin, and anatoxin-a have been defined and applied toward detection over the past decades. However, the biosynthetic pathway and genes for guanitoxin, the only known natural organophosphate neurotoxin, have yet to be described.Previously known as anatoxin-a(s), guanitoxin is an irreversible inhibitor of acetylcholinesterase, sharing an identical mechanism of action with organophosphates like the synthetic chemical warfare agent sarin and the banned pesticide parathion. Guanitoxin induces acute neurological toxicity that can lead to rapid death, showing comparable lethality (LD50 = 20 μg/kg i.p.) to saxitoxin, the most potent known cyanotoxin. Sporadic detection in the Americas, Europe, and Middle East coupled with bloom-related animal deaths consistent with guanitoxin exposure suggests that this toxin could be an under-recognized threat in global watersheds.