Using X-ray Crystallography and 1,n-ADEQUATE NMR to Revise the Structures of Highly Substituted Aromatic Natural Products: The Absolute Configuration of Formicamycin Congeners Formicamycins and their biosynthetic precursors, the fasamycins, form part of the phenylnaphthacenoid family of polyketide natural products. A recent atroposelective total synthesis of formicamycin H brought into question our original stereochemical assignment of the axially chiral linkage between C-6 and C-7. To address this, we obtained an X-ray crystal structure for formicamycin H that unambiguously confirmed our original assignment as the Sa atropisomer. X-ray structures for multiple additional fasamycins and formicamycins confirmed that this is common to all congeners. However, these studies identified a compounded error made by us whereby several structures previously reported as para-methoxy were found to have ortho-methoxy groups on the hanging E-ring. To address this for congeners that did not crystallize or gave nondiffracting crystals, we turned to the surprisingly underutilized 1,n-ADEQUATE NMR experiment. In total, we generated X-ray structures for 15 phenylnaphthacenoid metabolites and by combining these results report the corrected structures for three formicamycins, six fasamycins, and three biosynthetic lactone intermediates, noting that several revised fasamycin structures now match previously reported naphthacemycins. Our results highlight the utility of 1,n-ADEQUATE experiments for regiochemical determination in polysubstituted aromatic molecules. Moreover, our investigations uncovered a potential deracemization step during biosynthesis of the formicamycin framework.

New paper with @barriewilks.bsky.social. There are many reports on fasamycins and formicamycins (aka accramycins, naphthacemycins, streptovertimycins). Here, we unambiguously solve their structures and stereochemistry. A great effort, led by Dr Edward Hems

pubs.acs.org/doi/10.1021/...

I’m looking for an automated way to read others’s scientific data without giving credit or acknowledgement, and also claim full credit for insights from it. And I want it to have a fitting name

OAI: say no more

1. Dodgers
2. Whoever is playing the Giants.
3. Whoever is playing the Astros.

Congratulations to David Delgadillo and Jacob Rothbaum on being awarded the inaugural Nemko Mentorship Prize! 🎉

beckmaninstitute.caltech.edu/funding-opportunities/be...

My quote of the day

Science is the search for truth, that is the effort to understand the world: it involves the rejection of bias, of dogma, of revelation, but not the rejection of morality.

Linus Pauling

For a quick summary @uclacb.bsky.social al for the nice writeup of our paper www.chemistry.ucla.edu/news/innovat...

Mapping the Earth’s Hidden Fungal Kingdom | Joint Genome Institute Leveraging massive comparative genomics to decode millions of mystery genes and lay a future-ready foundation

“The enormous diversity of fungal genomes...offers catalogs of enzymes, secondary metabolites & other parts lists for biotechnology, bioenergy & biomaterials."—Igor Grigoriev, Fungal & Algal Program Head.
🖥️🧬🍄🍄‍🟫

jgi.doe.gov/user-science/science-sto...

Recent discoveries on the acquisition of the highest levels of human performance Scientists have long debated the origins of exceptional human achievements. This literature review summarizes recent evidence from multiple domains on the acquisition of world-class performance. We re...

Multidisciplinary training, over time, produces the highest impact people

www.science.org/doi/10.1126/...

The American Chemical Society held an evening reception on Sunday, the day before the official start of Pacifichem 2025, to celebrate its upcoming 150th anniversary year. Credit: Sara L. Cottle

Mona Nemer, Canada’s chief science advisor, gave the first plenary talk of the event, discussing the role of scientists as diplomats. Credit: Sara L. Cottle

A Pacifichem 2025 attendee receives a lesson in coconut frond braiding at the opening night reception. Credit: Sara L. Cottle

Pacifichem attendees learned how to braid ti leaves as part of a series of Hawaiian-themed activities at the opening night reception. Credit: Sara L. Cottle

Once every 5 years, scientists all over the world gather in Hawaii for the International Chemical Congress of Pacific Basin Societies: cen.acs.org/acs-news/mee...

#Pacifichem2025 #Pacifichem #chemsky 🧪

These archaea built a distinct genetic code to put pyrrolysine in proteins That feat has synthetic biologists excited

Because biology is so flexible, the genetic code is sometimes tweaked to add additional amino acids into select proteins. It turns out that some archaea, microorganisms distinct from bacteria and eukaryotes, have gone one step further. cen.acs.org/biological-c... #chemsky 🧪

Recurrent acquisition of nuclease-protease pairs in antiviral immunity Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin-like protease repeatedly acquired by multiple, ...

New in Science Magazine from the Doudna Lab and first author Owen Tuck: Recurrent acquisition of nuclease-protease pairs in antiviral immunity. Read here: https://ow.ly/pIWQ50XtEtM

Synthesis of Collinoketones via Biomimetic [6 + 4] Cycloaddition Cycloadditions are among the most powerful reactions for constructing molecular complexity. The archetypal example is the [4 + 2] (Diels–Alder) cycloaddition, which efficiently furnishes cyclohexene d...

[6+4] Cycloadditions! Introducing our first dive into this fascinating subject in a very enjoyable collaboration with Ken Houk and his team. Congrats to Harrison and Tufan!

pubs.acs.org/doi/10.1021/...

@dmeremin.bsky.social Absolutely crushed it with this automated workflow! It ain’t about the size of your crystals, nor the way that they look, that matters…it’s all about how they diffract! Cheers to the whole team!

Excited to share our latest @nature.com: How does naloxone (Narcan) stop an opioid overdose? We determined the first GDP-bound μ-opioid receptor–G protein structures and found naloxone traps a novel "latent” state, preventing GDP release and G protein activation.💊🧪 🧵👇 www.nature.com/articles/s41...

Structures from AlphaFold3 - while often impressively good - tend to fail representing the dynamic ensembles accurately. And often parts of the structure are not correct. Adding experimental data, directly in AlphaFold's diffusion step, provides physically realistic protein ensembles. This image shows two cases where AlphaFold3-only structures were largely improved by guiding with experimental data.

📢 New preprint:
Experiment-guided AlphaFold3 resolves accurate protein ensembles.
doi.org/10.1101/2025...

AlphaFold3 is incredible, but has crucial limitations: it typically collapses to a single conformation, ignoring the inherent dynamics of proteins. And it can be wrong. Here's a solution. 🧵👇

Screenshot that reads: The award "underlies the importance in investing in science for innovation and long-term economic growth", says economist Diane Coyle of the University of Cambridge. "It's great to see the Nobel prize recognize the importance of this topic," adds innovation policy researcher Richard Jones of the University of Manchester, UK. "It's important that economists understand the conditions that lead to technological progress," he adds. The winners, says Coyle, "have long been on people's list of potential candidates".

‘Economics Nobel prize won by researchers who showed how science boosts growth’ by @philipcball.bsky.social in @nature.com www.nature.com/articles/d41...

Metabolic controls on the carbon isotope fractionations of bacterial fermentation | PNAS Microbial fermentation facilitates the initial breakdown of organic matter into small molecules and is thought to be the rate-limiting step of anox...

Metabolic controls on the carbon isotope fractionations of bacterial fermentation www.pnas.org/doi/abs/10.1... #jcampubs

Prizes must recognize machine contributions to discovery The future of science will be written by humans and machines together. Awards should reflect that reality.

My HPLC was definitely overlooked

www.nature.com/articles/d41...

The 2025 chemistry Nobel goes to MOFs Susumu Kitagawa, Richard Robson and Omar M. Yaghi win the prize for developing metal–organic frameworks

The 2025 #NobelPrize in Chemistry has been awarded to Susumu Kitagawa, Richard Robson and Omar M. Yaghi “for the development of metal–organic frameworks.” Stay tuned for the full story to come! cen.acs.org/people/nobel...

#ChemNobel #Chem #Chemistry #chemsky 🧪

When was the NSF-GRFP eligibility change implemented? #chemsky

New electron diffraction strategy could make it easier to study solvated organic microcrystals The approach combines carbon liquid cells and rapid data acquisition to study solvated molecules at room temperature

A new electron diffraction technique could make it easier to study molecules that need to remain solvated at all times.

❄️ NEW PRE-PRINT ❄️ Happy to see our latest work online. Here we present a super simple solution to the preferred orientation problem in single particle cryo-EM: the use of ultrasonic excitation during vitrification! Details in the 🧵 below... #cryoEM #structuralbiology

The Radical S-Adenosyl-l-methionine Enzyme HydE Forms an Fe(I)Fe(I) Dimer En Route to the [FeFe] Hydrogenase H-Cluster [FeFe] hydrogenases are highly efficient metalloenzymes that catalyze hydrogen conversion via a sophisticated active site cofactor known as the H-cluster. Biosynthesis of its [2Fe]H subcluster, which ...

is the dimer core of the H-cluster of FeFe hydrogenase formed by rSAM chemistry in HydE?

pubs.acs.org/doi/full/10....

Trying to do more with less 🙂‍↕️

ACS Council approves the petition to establish the Committee on the Advancement of LGBTQ+ Chemists, 86% to 14%.

#chemsky 🧪⚗️ #acsfall2025

Scientists’ role in defending democracy The United States’ democratic leadership, commitment to freedom of expression, and investment in the pursuit of knowledge have long enabled its preeminence in science and technology. Yet today we are ...

Scientists’ role in defending democracy www.science.org/doi/10.1126/...

Let's all support this vital need: the ability to tell the truth. 💪

"Those in the science community who are willing & able to be more visible can step up. Acting together will be more impactful than going it alone."

Defending US democracy: the role of scientists
@science.org
www.science.org/doi/10.1126/...

#ChemSky #ACSFall2025 Huge thank you to Prof. Isaiah Speight, Prof. Kensha Clark, and Prof. Davita Watkins for organizing this amazing lineup of impressive speakers. Hosted by organicdivision.org POLY and INOR. Thank you to ACS President Dr. Phillips for elevating this to a Presidential Symposium

Jennifer Doudna is named 2026 Priestley Medalist The award recognizes the biochemist for discoveries on ribozyme function and CRISPR gene editing, and international science leadership

@acs.org is recognizing Jennifer A. Doudna with the Priestley Medal for her discoveries on ribozyme function, the Dicer RNase enzyme, double-stranded RNA processing, and CRISPR gene editing, along with her impactful international science leadership. cen.acs.org/people/award... #chemsky 🧪