With the recent arrival of the Zoalord Doctor Hamilcar Balcus at Relic's Point, events began to shift against the Guyvers. After quickly learning about the existence of the Enzyme type hyperzoanoid, Dr Balcus attempted to use these Guyver-Killers against the bio-boosted Humans but lacked all the data due to the loss of the Japanese Branch's headquarters. Thus, he was forced to remake the creatures but with his own modifications.
The first Enzyme II was optimized on Sho Fukamachi's father in order to provide a psychological reason for Guyver I to not kill the Zoanoid as he would be killing his own father. Enzyme II succeeded in severely damaging Guyver I's brain in battle when the control medal took over the body of the host and destroyed Enzyme II.
A group of three Enzyme II's were dispatched in their Human forms against the Guyvers. Approaching the group, they morphed and attacked their jeep caravan. However, whilst expecting the two Guyvers, only Agito Makishima morphed into his bio-boosted form as Sho Fukomachi's sub-conscious had repressed the memory of him killing his father as the first of the Enzyme II's. This prevented from bio-boosting leaving Makishima to attack the Hyperzoanoids. They almost defeated the lone Guyver except for the intervention of Mr Murakami who revealed his identity as a proto Zoalord test body who destroyed the Enzyme II's in a short amount of time.
Three Enzymes II's were rushed from their Optimization tanks by Richard Guyot as part of his assault against Guyver I, III, Mister Murakami and their friends. Catching up with them, the three Enzyme II's morphed into their combat form where they battled against Guyver III and the proto Zoalord Mr Murakami. The Enzyme II's proved to be an effective weapon and nearly killed Guyver III but began dying as a result of their rushed Optimization and began to melt mid battle.
The second Enzyme zoanoids were notably different from the first forms. They shared a similar body with furry white fur on their forms with batches of black chitin. Their faces had a more insectoid looking shape with four red eyes and a mouth full of mandibles. This form lost their tails but made up for this deficiency with four spear-like limbs stretching from the back. It was capable of using these insect-tile limbs to spear its enemies that approached the zoanoid.
Similar to the Enzyme I's, the second Enzyme possessed an acidic form of blood which was capable of dissolving even bio-boosted armor. This meant that any melee attack against the Hyperzoanoid had the capacity of dealing damage on the one inflicting it.
- Mark Hamill's character within the Guyver Mutronics movie was forcibly transformed into a Zoanoid that bore some resemblance to Enzyme.