Sayyid, Fatima and Ahmad Nadzirin, Izzuddin and Abdul Hamid, Azzmer Azzar and Alias, Norsyuhada
(2025)
In silico screening of microbial metabolites reveals Moromycin B as a potential pancreatic lipase inhibitor.
In: 1st International Biomedical Conference 2025, 3 - 4 September 2025, AC Marriot Hotel, Kuantan.
Abstract
INTRODUCTION: Obesity is a chronic, multifactorial disease contributing to health burdens worldwide.
An established therapeutic strategy involves inhibiting pancreatic lipase, the enzyme responsible for
dietary fat breakdown in the digestive system. Inhibiting this enzyme prevents fat absorption and
promotes excretion, which leads to weight loss. Currently, orlistat is the only FDA-approved pancreatic
lipase inhibitor, but its gastrointestinal side effects call for safer alternatives, particularly from natural
resources. Microbial metabolites, known for their structural diversity and bioactivity, offer promising
potential. This study leverages in silico screening to discover novel microbial metabolites capable of
inhibiting pancreatic lipase.
OBJECTIVE(S): To identify microbial metabolites that inhibit pancreatic lipase through in silico
screening, and to evaluate their interactions with the enzyme’s key catalytic residues, Ser152, His263,
and Asp176.
MATERIALS & METHODS: The structure of human pancreatic lipase (PDB ID: 1LPB) was retrieved
from the Protein Data Bank, and 36,454 microbial metabolites were sourced from Natural Product
Atlas. Drug-likeness was filtered using Lipinski’s Rule of Five. Molecular docking was conducted
using AutoDock Vina, with orlistat as a reference. Top hits were analysed using the Protein-Ligand
Interaction Profiler (PLIP) and visualised in PyMol.
RESULTS: Out of 36,454 metabolites screened, 27,297 passed Lipinski’s filter. Among them,
moromycin B, which is derived from Streptomyces, exhibited the highest binding affinity (-13.2 kcal/
mol), surpassing that of orlistat (-6.7 kcal/mol). Moromycin B formed a hydrogen bond with the catalytic
residue Ser152, suggesting favourable and potentially stable interactions within the enzyme’s active
site.
CONCLUSION: This in silico study identified moromycin B as a promising microbial inhibitor of
pancreatic lipase. While previously recognised for its anticancer properties, its strong binding affinity
and favourable interaction with a key catalytic residue in this study suggest a novel therapeutic
application as an anti-obesity agent.
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