See haukex's article Building Regex Alternations Dynamically:

Win8 Strawberry 5.8.9.5 (32)  Sat 10/01/2022 17:18:27
C:\@Work\Perl\monks
>perl

use strict;
use warnings;

use Data::Dump qw(dd);  # for debug

my $text = <<'TEXT';
Regular expressions have the undeserved reputation
of being abstract and difficult to understand.
TEXT
print "before ---$text--- \n";

my @regexlist = split /\n/, <<'REGEX';
a A
i I
e E
REGEX

my %replace = map split, @regexlist;
# dd \%replace;  # for debug

my ($rx_search) =
    map  qr{ $_ }xms,
    join ' | ',
    map  quotemeta,
    reverse sort
    keys %replace
    ;
# dd $rx_search;  # for debug

$text =~ s{ ($rx_search) }{$replace{$1}}xmsg;
print "after +++$text+++ \n";

^Z
before ---Regular expressions have the undeserved reputation
of being abstract and difficult to understand.
---
after +++REgulAr ExprEssIons hAvE thE undEsErvEd rEputAtIon
of bEIng AbstrAct And dIffIcult to undErstAnd.
+++
[download]

Update: This approach assumes each text file can be slurped to memory; 2-100 MB should be no problem. It also assumes the number of substitutions is "reasonable"; 150-1000 should be no problem. Care must be exercised in building the $rx_search regex if it is more complex than shown in the example; see haukex's article for tips on this. I have no idea how fast this approach is versus the one you're using now. Good luck :)

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