Evidence map›Paper›PMID 42414636›Full record

ArticleNature chemical biology2026

Structural and biochemical basis for cannabinoid cyclase activity in marine bacterial flavoenzymes.

Anna C Love, Harshverdhan Sirohi, Felix M Hubert, Ying-Chieh Kao, Daniel E Quinnell, Tian Lan, Ryan Gappy, Marissa Sheehy, Jonathan Hsu, Adrian Lee and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemical biology, 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

5 · Who and what money

Authors and funding

15 authors.

Anna C Love *Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5657-2858
Harshverdhan Sirohi *Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
Felix M Hubert *Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA.
Ying-Chieh KaoSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
Daniel E QuinnellSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
Tian LanCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA.
Ryan GappyCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0008-2965-2156
Marissa SheehyCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA.
Jonathan HsuSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0006-0535-8329
Adrian LeeSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
Liana ZangwillCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0007-5997-5215
Timothy ChangSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
Bruce A PalfeyDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Geoffrey ChangSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA. g1chang@health.ucsd.edu.ORCID http://orcid.org/0000-0002-7476-9010
Bradley S MooreCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA. bsmoore@ucsd.edu.ORCID http://orcid.org/0000-0002-4652-1253

Funding

Biosynthesis and biological mechanism of minor cannabinoidsR01AT012641 · NCCIH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEROLD CHUN, BRADLEY S MOORE · 2024 to 2026
$2.1M
Chemoenzymatic synthesis and pharmacological evaluation of designer plant meroterpenoidsF32GM150232 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOVE, ANNA CLAIRE · 2023 to 2025
$221k
NCCIH NIH HHS R01 AT012641NIGMS NIH HHS F32 GM150232U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1F32-GM150232-02U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1R01-AT012641
6 · The paper itself

Abstract

The marine bacterial flavoenzymes Clz9 and Tcz9 can process cannabigerolic acid to the minor cannabinoid, cannabichromenic acid (CBCA); however, the mechanistic details of this extrinsic transformation are still obscure. Here we report a thorough analysis of CBCA formation by Clz9 and Tcz9 through high-resolution crystallographic characterization, biochemical analysis and spectroscopic interrogation. Our work reveals that Clz9 and Tcz9 use different biochemical mechanisms from Cannabis cyclases and each other in their production of CBCA. Collection of a high-resolution substrate-bound structure provides additional key insights into how active site architecture affects substrate binding and stereoselectivity. Engineering approaches improve the stereoselectivity of CBCA formation by Clz9 and Tcz9, providing access to (R) and (S)-CBCA. Collectively, our work advances understanding of enzymatic cannabinoid formation and cements Clz9 and Tcz9 as two unique members of the BBE-like enzyme family with encouraging potential for biocatalytic cannabinoid production applications.

Identifiers

PMID42414636
PMCPMC13623302

What OpenQuestion holds

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Registered trials

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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.