 It's nicknamed the humongous fungus, and for good reason. This colony of armillaria gallica, a type of honey mushroom, stretches across an area the size of 28 football fields beneath the Crystal Falls, Michigan, and weighs in at a whopping 95 metric tons. Scientists estimate the colony's age to be approximately 1,500 years old, but size and longevity aren't the only things that make this species of mushroom special. Armillaria are the only known organisms to produce mellialides and armillil or selenates, natural compounds with potent antimicrobial and anti-cancer properties. Now, researchers have isolated the cluster of genes responsible for manufacturing these powerful chemicals, paving the way toward artificial means of ramping up their production. The team led by Stefan Jenerwein had previously isolated the pathway committing proto-illudine synthase, Gene Pro-1. Pro-1 encodes for a terpene cyclase that ultimately leads to the production of the coveted molecules for which armillaria are prized. In this gene, they have found the key to unlocking a treasure trove of medicinal compounds. But what was missing were the critical steps and biosynthetic intermediates in between. The team assumed that the genes coding for biosynthetic enzymes that lie on the same biosynthetic pathway tend to be clustered in the fungal genome. Thus, they believed they could find those missing steps by cloning the genes surrounding the Pro-1 gene. That led to the discovery of four genes coding for cytochrome P450-dependent monooxygenases in the vicinity of Pro-1 in the armillaria genome. Functional expression of the cytochrome P450 genes identified one of them as the gene coding for proto-illudine-8 alpha hydroxylase, which catalyzes the committing step into the armillil or selenate pathway. When engineered into a strain of yeast, that protein produced this intermediate in quantities large enough for structural confirmation using NMR spectroscopy. Much work still remains to be done, as much of the biochemical pathway that leads directly to armillaria's most potent natural products still remains unknown. Researchers will continue to explore the genetic neighborhood surrounding Pro-1 for more clues. And hopefully one day, they'll crack the code that enables the mass production of armillaria's chemical arsenal against human diseases and cancer.