Nitrene generation and transfer for unnatural biosynthesis in living cells.

Isaac Donnell, Andrew Quest, Jeremy Tang, Maodun Zhang, Brandon Bloomer, Douglas S Clark, Aindrila Mukhopadhyay, John Hartwig, Jay D Keasling

Abstract read

PubMed Publisher

In one paragraph

Article in Nature chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Isaac Donnell *Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.

Andrew Quest *Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0004-5081-3664

Jeremy TangCollege of Natural Resources, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0003-9152-9777

Maodun ZhangDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.

Brandon BloomerDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.

Douglas S ClarkDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-1516-035X

Aindrila MukhopadhyayJoint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA, USA.ORCID http://orcid.org/0000-0002-6513-7425

John HartwigDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA. jhartwig@berkeley.edu.ORCID http://orcid.org/0000-0002-4157-468X

Jay D KeaslingJoint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA, USA. keasling@berkeley.edu.ORCID http://orcid.org/0000-0003-4170-6088

Funding

DOE | Office of Science (SC) DE-AC02-05CH11231National Science Foundation (NSF) 2027943

6 · The paper itself

Abstract

Synthetic biology has enabled the production of natural and unnatural products from inexpensive sustainable feedstocks. Yet, the scope of available products has been limited largely to compounds accessible from nature's chemical reactions. Evolved enzymes can catalyse reactions of unnatural substrates or reactions not found in nature but often require the addition of synthetic reagents to purified enzymes or to resting cells containing those enzymes. Here we show that chemical reactions of metabolic intermediates produced intracellularly in living cells can include intermolecular nitrene transfers. The biosynthesis of N-acetoxyanilines, in combination with the generation and transfer of N-aryl nitrene intermediates from them catalysed by a cytochrome P450, generates amino alcohols, diamines, diarylamines and aminoalkyl arenes from simple carbon feedstocks. These products-common substructures of pharmaceuticals and agrochemicals-are challenging to synthesize by standard organic chemistry and were produced from inexpensive, renewable feedstocks. Evolution of the enzymes in this pathway showed that titres can be increased by engineering and that the products can be synthesized with high enantioselectivity.

Identifiers

PMID42613447

DOI10.1186/1472-6750-8-91

What OpenQuestion holds

Textmetadata

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.