publications

2026

1. Unified genomic and chemical representations enable bidirectional biosynthetic gene cluster and natural product retrieval

   Guimei Liu, Yiting Li, Gabriel Ong, and 5 more authors

   Scientific Reports, May 2026

   Abs DOI

   Natural product discovery is increasingly driven by the ability to analyze microbial genomes for biosynthetic gene clusters (BGCs) that encode secondary metabolites. While existing approaches have successfully linked BGCs to broad classes of chemical products, they typically operate in a single modality (genomic or chemical) limiting the scope of bidirectional prediction. In this work, we propose a multimodal framework that integrates genomic and chemical information by projecting embeddings derived from pretrained language models into a common representation space. We embed genomic sequences using a BGC foundation model and represent molecules through a chemical language model, then use a metric learning model to co-embed BGCs and their associated chemical structures. This co-embedding space allows us to quantify the similarity between BGCs and compounds using similarity measures, enabling both efficient forward and inverse retrieval tasks. Our approach consistently outperforms the non-alignment approach and represents a generalizable, scalable strategy to bridge biological and chemical modalities in natural product discovery.

2. 

   Design of a Labile RNase A Using Protein Language Models

   Gabriel Ong, Kiat Whye Kong, Si En Poh, and 3 more authors

   ACS Synthetic Biology, Jan 2026

   PMID: 41348585

   DOI

2025

1. 

   Paradigms of convergent evolution in enzymes

   Ioannis G. Riziotis, Jenny C. Kafas, Gabriel Ong, and 3 more authors

   The FEBS Journal, Mar 2025

   Abs DOI

   There are many occurrences of enzymes catalysing the same reaction but having significantly different structures. Leveraging the comprehensive information on enzymes stored in the Mechanism and Catalytic Site Atlas (M-CSA), we present a collection of 34 cases for which there is sufficient evidence of functional convergence without an evolutionary link. For each case, we compare enzymes which have identical Enzyme Commission numbers (i.e. catalyse the same reaction), but different identifiers in the CATH data resource (i.e. different folds). We focus on similarities between their sequences, structures, active site geometries, cofactors and catalytic mechanisms. These features are then assessed to evaluate whether all the evidence for these structurally diverse proteins supports their independent evolution to catalyse the same chemical reaction. Our approach combines published literature information with knowledge-based computational resources from, amongst others, M-CSA, PDBe and PDBsum, supported by tailor-made software to explore active site structures and assess similarities in mechanism. We find that there are multiple types of convergent functional evolution observed to date, and it is necessary to investigate sequence, structure, active site geometry and enzyme mechanisms to describe such convergence accurately.