Evidence map›Paper›PMID 40789944›Full record

ArticleNature chemical biology2026

Biosynthesis of the α-D-mannosidase inhibitor (-)-Swainsonine.

Shaonan Liu, Zainab Batool, Yang Hai

Abstract read
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. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Shaonan LiuDepartment of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, USA.ORCID 0009-0001-7864-9534
Zainab BatoolDepartment of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, USA.
Yang HaiDepartment of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, USA. hai@chem.ucsb.edu.ORCID 0000-0002-2039-5367

Funding

Understanding the specificity and non-native catalytic activity of PLP-dependent enzymesR35GM151205 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI Yang Hai · 2023 to 2026
$1.8M
NIGMS NIH HHS R35 GM151205U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM151205
6 · The paper itself

Abstract

(-)-Swainsonine is a polyhydroxylated indolizidine alkaloid with potent inhibitory activity against α-D-mannosidases. Although the genetic basis of its biosynthesis has been established, the biosynthetic mechanism underlying its formation remains poorly understood. Here we report the complete elucidation of the biosynthetic pathway through a combination of in vivo and in vitro reconstitution studies. Our findings reveal an unexpected epimerization mechanism mediated by two bifunctional α-ketoglutarate-dependent nonheme iron dioxygenases, SwnH2 and SwnH1, along with an unusual imine reductase, SwnN, which exhibits substrate-dependent stereospecificity. We further discovered that an O-acetyl group can serve as a detachable directing group that modulates the site selectivity of SwnH2-catalyzed hydroxylation without altering its stereoselectivity. These mechanistic insights into Swainsonine biosynthetic enzymes enable biocatalytic synthesis of an unnatural polyhydroxylated indolizidine alkaloid, opening doors to the biosynthesis of structurally diverse natural product-derived glycosidase inhibitors.

Indexed as

alpha-MannosidaseEnzyme InhibitorsSwainsonineHydroxylationStereoisomerismSubstrate Specificityalpha-MannosidaseEnzyme InhibitorsSwainsonine

Identifiers

PMID40789944
PMCPMC12466120

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.