Cities Skylines - Not enough goods and not enough purchasers

I have done everything possible to supply goods to commercial and demand for generic industry. I have balanced the amount of commercial with the amount of industry, I have cargo train terminals everywhere and two ports for ships to bring raw materials and goods. I have also developed the oil, ore, forestry and farming industries. Finally, I have a perfect road system. Yet, when my cities reach a population over 300,000, commerce states "not enough goods" and industry states "not enough raw materials" or "not enough purchasers." Then both sectors go into a death spiral of abandoned buildings. One thing I have done recently, since I got a super computer, is buy 25 tiles of land. I have heard the game is designed for only 9 tiles. So, what is causing my problem with commerce and generic industry?

Possible cause: Caps.

You state that the problem only occurs after a certain population. Cities Skylines limits the amount of agents that can be active transporting goods and people in a city at the same time. If you reach this limit, there just may not be enough vehicles available for you to get your production chains working.

To work around this limitation, you can either reduce transportation distance or time, by building highways, cargo rail, or putting the zones closer together. Supplying better mass transit will also help, as the agent pool is shared. You can also look for mods that raise these limits.

Another possible cause: Resource depletion

This is caused by the natural tendency of certain resources (oil and ore) to deplete over time. You will need to install a mod to prevent this.