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Preheat oven to 425°F. Lightly oil a 9-by-13-inch baking dish. Cook pasta according to package directions. Drain.
Heat 2 tablespoons oil in a large pot over medium heat. Add cauliflower, garlic, and onion. Season with salt. Cook, covered, stirring occasionally, until tender, 15 to 20 minutes. Add 4 cups water and simmer until vegetables are very soft, 10 to 12 minutes. Drain, reserving 2 cups cooking liquid; let cool slightly.
Combine vegetables, Cheddar, Parmesan, mustard powder, and cayenne in a blender (depending on the size of your blender, you may need to do this in two batches). Purée, adding just enough reserved cooking liquid to get mixture moving, until smooth, 1 to 2 minutes.
Add sauce to pasta and toss to combine. Transfer to prepared baking dish. Toss together panko, parsley, and remaining tablespoon oil in a bowl. Season with salt and pepper. Sprinkle over pasta. Bake until golden brown, 14 to 16 minutes.