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The group provided a well-organized article on the mechanism of tryptophan 7-halogenase. They used 7 references for their article. The article is well-written and I personally think the tone is encyclopedic. For spelling or grammar, everthing is good. I just have a concern on some words like “7 position” or “2 position”. I think the authors want to mention “C7 position” and “C2 position”. In case the authors want to expand their writing on the mechanism, here are my suggestions: 1/. Be more extensive in the regiochemistry part, especially provide a Pymol picture which can illustrate better the structure of the tunnel and a comparison between position C2 and C7 of tryptophan’s indole ring in the active site of the enzyme. Also, giving more detail about tryptophan 5-halogenases is suggested as they mentioned it at the end but did not clarify what tryptophan 5-halogenases can benefit from having carbon 5 in the end of the tunnel. 2/. Give a short description on the mechanism proposed by Flecks et al as it does not include the formation of the chloramine species which is a more common concept. Did Flecks et al propose any intermediate species? 3/. Also are there any recent updates on the halogenation step as three references used in this part (mostly reference 7) are published in 2005 and 2007? 4/. The first and third paragraphs of “Halogenation mechanism” are not linked to any reference, so it is not clear if they are written based on the reference 4, 7 and 8. 5/. Provide the caption for the images. The authors have great images though. 6/. The authors mentioned in the last paragraph that the enzyme has been studied using X-ray crystallography, so in my opinion, it can be better if the authors also briefly mention the methods employed to arrive at the conclusions on the mechanism mentioned right before that. Thanks. Nhat Do. Nhattrongdo (talk) 01:19, 4 March 2017 (UTC)[reply]