Identified engineered pathway from human gut microbiome data

Hi there,

I’m running Humann 3.0 and matched the pathway with metacyc. It turns out one of the pathway is an engineered pathway, which does not naturally occur in any known organism and is constructed from metabolic engineering…

My data are from human gut microbiome… So I was wondering if it means something wrong with the mapping or I should just drop this pathway for downstream analysis. Thanks in advance!

A couple of ideas:

  1. If this pathway is showing up at the community level, it could be because the species in the community collectively satisfy all of its reactions (even though no single species does, consistent with the MetaCyc description).

  2. HUMAnN will gap-fill up to 1 missing reaction to boost sensitivity (you can turn this off if desired). If we are gap-filling a reaction that should legitimately be absent, then we may be assigning this pathway to species as a false positive. In that case there is probably a very similar version of the pathway (sharing most of the reactions) that the species legitimately encodes. I’ve seen this happen a lot with MetaCyc because they often define multiple subtly different variants on a pathway and they can be hard to tell apart from noisy metagenomic data.