110 Followers
56 Following
44 Posts

A sidero-10 among siderophores 🦠

Postdoc at Wageningen University | Bioinformatician | Bioinorganic chemist | they/them 🏳️‍🌈

Twitter handle: @ZachReitzPhD

Natural product researchers, do you first hear about conferences when the live tweets start or your PI leaves? I've started a list of upcoming events that feature work on secondary/specialized metabolites!

Please share and help me expand the list!
https://docs.google.com/spreadsheets/d/1-82Of7B0pjo3TqkCuIWDjqZHvceB_5VvhayLUeYtnSQ/edit#gid=0

Natural Products Conferences, Symposia, and Workshops

Upcoming events This is a list of upcoming conferences, symposia, and workshops that may be of interest to researchers working on natural products (particularly secondary/specialized metabolites) Submissions are encouraged! Please enter new events on the NEW SUBMISSIONS sheet (second tab below),...

Google Docs

AntiSMASH NRP metallophore prediction has only been out for three days and it already needs an update 🙃

Congratulations to Qihao Wu et al on finding a new class of metallophores! I'm looking forward to a full read and exploring that BGC!

https://pubs.acs.org/doi/10.1021/jacs.2c06410#.Y6H5AxGDwAc.twitter

PS: I added antiSMASH detection for three other families of metallophores: aminopolycarboxylic acids, methanobactins, and opine-like metallophores.

You'll also notice that "siderophore" clusters are now listed as "NRPS-independent-siderophore", so that the label matches the name of the biosynthetic pathway rather than the (assumed!) biological function

So what's next?

Well as for me, I'm looking for my next step! I've had a fantastic postdoc with @marnixmedema, but it will soon be time for me to move on. I'm looking for a position, possibly remote, that will allow me to return to my home in sunny Santa Barbara, California. If you have any leads, please let me know!

And as for metallophore discovery? We already have plans for an expanded full paper, so stay tuned!

Mapping the BGCs to a species phylogeny from GTDB allowed us to see who's making (detectable) NRP metallophores. We found BGCs in 60% of Myxobacteria, 41% of Cyanobacteria, 35% of Actinobacteria, 18% of Proteobacteria, and just 3.3% of Firmicutes. Few were found outside these phyla.

Where can we find biosynthetic novelty? Cyanobacteria! We found them to be severely understudied. Nearly all BGCs were distinct from each other and from the two (!) known cyanobacterial NRP metallophores.

I applied the rules to 15k bacterial genomes to generate the first global census of NRP metallophore biosynthesis in bacteria (but certainly not the last!)

BiG-SCAPE networking showed that many BGCs are unlike anything found in MIBiG, and nearly 500 were only found in a single species! We also identified a couple of chelator combinations not found in any known BGCs

NRP metallophores have chelating substructures rarely found in other natural products, and genes encoding chelator biosyntheses are often in the BGC alongside the NRPS. I developed a series of HMMs to detect those chelator pathways.

Using this (not-so-)simple strategy, we could identify 78% of NRP metallophore BGCs with just a 3% false positive rate.

How do I know? Expert examination is still the best way to find metallophore BGCs, so I manually annotated 758 NRPS BGCs as a gold standard!

I'm pleased to announce that antiSMASH can now predict if an NRPS BGC produces a metallophore!

Check out our new preprint for all the details:
https://www.biorxiv.org/content/10.1101/2022.12.14.519525v1

I tested the new algorithm on 15k bacterial genomes. NRP metallophores make up an astounding 25% of all NRPS BGCs! This thread will have some more highlights.

Test it out on the antiSMASH website and let me know what you think!
https://antismash.secondarymetabolites.org/#!/start
(You may have to clear your cache for "Enable antiSMASH beta" to appear)

ChatGPT is so fun

(RT me:)
Check out @ButlerLabUCSB's "In a Nutshell" article, just published in @FEBS_Letters!

https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14539

In 2016, we dreamed up three hypothetical siderophores, and I set out to find them using genome mining. We've now isolated them all! (1/n)

Full thread:
https://twitter.com/ZachReitzPhD/status/1598700136036605953