Skip to content
DraconiticResearch
Search Sources API
190,851 studies31 sourcesUpdated 37 min ago
PreprintCC BYbioRxiv

SpiE is a distinct gut microbial 4-cholesten-3-one 5β-reductase that acts with SpiR to convert cholesterol to coprostanol

  • A. K. Jiang1
  • G. Arp
  • M. Kato
  • T. Brunner
  • M. R. Grant
  • A. M. Clarke
  • A. M. Sidebottom
  • M. McMillin
  • C. J. Lehmann
  • M. A. Odenwald
  • K. S. Wolfe
  • B. Patel
5 more authors
  • O. Odenike
  • Y. Li
  • S. H. Light
  • B. Hall
  • X. Jiang1
  1. 1National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
Read full textPDFDOICite

Abstract

Gut microbes convert cholesterol into coprostanol, a poorly absorbed sterol that is largely excreted in feces and is linked to lower serum cholesterol levels. However, the enzymes responsible for this process remain poorly characterized. The second step of the pathway, cholestenone reduction into coprostanone, has long been established, yet the enzyme(s) responsible were unknown. Here, we use comparative genomics to identify SpiE, a cholestenone (4-cholesten-3-one) reductase that is part of the steroid processing (spi) pathway with SpiR. We confirm that SpiE binds to and reduces both cholestenone and progesterone into 5{beta}-reduced forms. SpiR and SpiE together convert cholesterol into coprostanol, indicating that both enzymes are sufficient for coprostanol formation. SpiE belongs to the short-chain dehydrogenase (SDR) family and represents an evolutionarily distinct lineage of SDR ene-reductases. Metagenomic analyses reveal that spiE relative abundance is strongly correlated with stool coprostanol (Spearman's {rho}=0.81, p=5.99e-65). In longitudinal patient cohorts, antibiotic treatment coincided with loss of SpiE and coprostanol production. Post antibiotics, the emergence of distinct SpiE-encoding genera rescued coprostanol production in some individuals. Our findings provide the biochemical basis of the cholesterol to coprostanol pathway and lay the groundwork for future studies linking it to host physiology.

Related

  1. Invasive Chinese tallow is associated with distinct rhizosphere microbial communities, core microbiomes, and functional potential relative to native Loblolly pine
    M. Khan, B. Pant, A. H. Kabir
    bioRxivPreprintAll rights reservedFull textEcologybioRxiv
  2. Distinct kinetics and mechanisms of microbial inactivation of enteric virus revealed by capsid and genome integrity
    J. Meibom, L. D. Morales, H. K. Wynn +2
    bioRxivPreprintCC BYFull textMicrobiologybioRxiv
  3. Long-read shotgun metagenomics identifies distinct urogenital microbial community states associated with functional potential and urinary tract infection during pregnancy
    M. Fontes Noronha, B. Ferneyhough, M. J. Roddis +2
    bioRxivPreprintCC BYFull textMicrobiologybioRxiv
  4. Automated compartment-based quantification reveals distinct patterns of cutaneous innervation with aging and microbial colonization
    H. Le Chang, M. Lee, L. Schneider +4
    bioRxivPreprintCC BYFull textNeurosciencebioRxiv
  5. Reconstitution of the Trimethylamine Oxide Reductase Regulatory Elements of Shewanella oneidensis in Escherichia coli
    Stéphanie Gon, Jean-Claude Patte, Jean-Philippe dos Santos +1
    Journal of BacteriologyPeer-reviewedLicence not stated36 citedMicrobiologyHAL

Cite

BibTeXRIS
BibTeX
@misc{jiang2026spie,
  title = {{SpiE is a distinct gut microbial 4-cholesten-3-one 5β-reductase that acts with SpiR to convert cholesterol to coprostanol}},
  author = {A. K. Jiang and G. Arp and M. Kato and T. Brunner and M. R. Grant and A. M. Clarke and A. M. Sidebottom and M. McMillin and C. J. Lehmann and M. A. Odenwald and K. S. Wolfe and B. Patel and O. Odenike and Y. Li and S. H. Light and B. Hall and X. Jiang},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.06.757028},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.06.757028v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - SpiE is a distinct gut microbial 4-cholesten-3-one 5β-reductase that acts with SpiR to convert cholesterol to coprostanol
AU  - A. K. Jiang
AU  - G. Arp
AU  - M. Kato
AU  - T. Brunner
AU  - M. R. Grant
AU  - A. M. Clarke
AU  - A. M. Sidebottom
AU  - M. McMillin
AU  - C. J. Lehmann
AU  - M. A. Odenwald
AU  - K. S. Wolfe
AU  - B. Patel
AU  - O. Odenike
AU  - Y. Li
AU  - S. H. Light
AU  - B. Hall
AU  - X. Jiang
PY  - 2026
DA  - 2026/10/06
PB  - bioRxiv
DO  - 10.64898/2026.10.06.757028
UR  - https://www.biorxiv.org/content/10.64898/2026.10.06.757028v1
AB  - Gut microbes convert cholesterol into coprostanol, a poorly absorbed sterol that is largely excreted in feces and is linked to lower serum cholesterol levels. However, the enzymes responsible for this process remain poorly characterized. The second step of the pathway, cholestenone reduction into coprostanone, has long been established, yet the enzyme(s) responsible were unknown. Here, we use comparative genomics to identify SpiE, a cholestenone (4-cholesten-3-one) reductase that is part of the steroid processing (spi) pathway with SpiR. We confirm that SpiE binds to and reduces both cholestenone and progesterone into 5{beta}-reduced forms. SpiR and SpiE together convert cholesterol into coprostanol, indicating that both enzymes are sufficient for coprostanol formation. SpiE belongs to the short-chain dehydrogenase (SDR) family and represents an evolutionarily distinct lineage of SDR ene-reductases. Metagenomic analyses reveal that spiE relative abundance is strongly correlated with stool coprostanol (Spearman's {rho}=0.81, p=5.99e-65). In longitudinal patient cohorts, antibiotic treatment coincided with loss of SpiE and coprostanol production. Post antibiotics, the emergence of distinct SpiE-encoding genera rescued coprostanol production in some individuals. Our findings provide the biochemical basis of the cholesterol to coprostanol pathway and lay the groundwork for future studies linking it to host physiology.
ER  -