If the source is 10 bit - maybe not. If the source is 8 bit - waste of time.
Here are some bulletproof Handbrake Settings - adjust the bit rates to suit yourself, but the encodes will be solid - and generally Direct Play on everything in the Plexiverse:
As for Audio - you can maintain the original track in an MKV file as track 2, but you should create a Direct Playable audio track in slot one - whatever that has to be.
I use AC3-5.1, the Roku passes it along to the TV and the TV is quite happy doing a great job from there on it’s own.
Xmedia Recode is invaluable in the audio converting and juggling area - but without a Mac Flavor - won’t help you - unless you have PC capabilities.
Handbrake can do the audio easily enough tho:
Create 2 audio tracks using the best available - pass through the second track - convert the first track to something that will Direct Play. Find out what that is and create the best one that will Direct Play.