$re = '/^(\s*(?<!#)\s*PRIMER_PRODUCT_SIZE_RANGE\s*)=.*$/m';
$str = '# PRIMER_PRODUCT_SIZE_RANGE=xxx-yyy
PRIMER_PRODUCT_SIZE_RANGE=100-300
PRIMER_NUM_RETURN=3
PRIMER_MAX_END_STABILITY=9.0
PRIMER_MAX_HAIRPIN_TH=24.0';
$subst = "\1=500-300";
$result = preg_replace($re, $subst, $str);
echo "The result of the substitution is ".$result;
Please keep in mind that these code samples are automatically generated and are not guaranteed to work. If you find any syntax errors, feel free to submit a bug report. For a full regex reference for PHP, please visit: http://php.net/manual/en/ref.pcre.php