Have four things ready before you enquire
The date, or a window. The audience, in a sentence that says who they are rather than how many. The job the talk has to do, which is the one most enquiries leave out and the one that changes the talk most. And your budget range, even roughly.
An enquiry with those four gets a real answer. An enquiry that says only "are you available in the spring" gets a question back, and you have lost a week.
Direct or through a bureau
A bureau handles contracting, logistics and payment, and takes a margin for it. That is genuinely worth it if you are running a large programme with many speakers and no time.
Going direct is faster and there is no margin in the middle. You will do the contract yourself. For a single keynote it is usually the better trade, and it also means the person shaping the talk is the person giving it rather than an account manager relaying notes.
One thing to check either way: whether the speaker has an exclusivity arrangement with a bureau that restricts direct booking. Ask early, because it changes who you should be talking to.
What actually moves the fee
Travel and the number of days it costs, more than anything else. A talk that needs two flights and three days is a different booking from one down the road, whatever is on stage.
Preparation. A keynote built to your theme, your sector and your programme takes real work; the same talk delivered off the shelf does not.
Extras. A workshop, a panel, a customer dinner or a recording you intend to publish are each a separate thing to agree rather than a favour to ask on the day.
The timeline
Enquire as early as you have a date, even provisionally. Good dates go first and an early conversation costs neither side anything.
Expect the shape to be settled a month or two out and the actual content in the weeks before, because a talk written too early is a talk that has stopped being about your event.