Cook the pasta. Preheat the oven to 350 degrees. Bring a large pot of generously salted water to a roaring boil. Cook the pasta 1 minute under the suggested al dente cooking time. Drain the pasta and set it to the side.
Make the sauce. Place a medium sized pot over medium heat. Melt the butter, then add the all purpose flour. Mix to combine. Add one cup of milk to the pot, then stir until it is well combined and there are no clumps. Add the rest of the milk and reserved pasta water, then place it over high heat and bring it to a boil. Once it begins to boil, reduce the heat to medium high, then add the cheese. Stir constantly until the cheese is melted and combined. Add the salt, garlic powder, onion powder, and ground mustard. Stir to combine, then remove it from the heat.
Season the panko crumbs. In a small bowl, combine the panko bread crumbs and butter. Stir until the breadcrumbs are evenly coated. Set it to the side.
Bake the mac and cheese. Combine the pasta and sauce in a large pot and stir until the pasta is evenly coated. Place the mac and cheese in a large baking dish, then top it with the panko breadcrumbs. Place the baking dish in the oven and bake for 20-25 minutes, until the panko breadcrumbs are golden.
Serve. Remove the mac and cheese from the oven and serve immediately. Mangia!