const regex = /(me)(?!([^<]+)?>)/gi;
// Alternative syntax using RegExp constructor
// const regex = new RegExp('(me)(?!([^<]+)?>)', 'gi')
const str = `I have ever been prone to seek adventure and to investigate and experiment where <span class='me'>wiser men</span> would have left well enough alone.`;
const subst = `<span class='highlight'>$1</span>`;
// The substituted value will be contained in the result variable
const result = str.replace(regex, subst);
console.log('Substitution result: ', 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 JavaScript, please visit: https://developer.mozilla.org/en/docs/Web/JavaScript/Guide/Regular_Expressions