McKenna Loop Yao

All Publications

• The biosynthetic gene cluster landscape of the oral microbiome across health and dental caries JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY Yao, M., Lin, P., Hua, K., Zhang, W. 2026; 53

  Abstract

  Specialized metabolites encoded by biosynthetic gene clusters (BGCs) in the oral microbiome remain largely unexplored in the context of oral health and disease. Previous genome-centric surveys have identified hundreds of uncharacterized BGCs in the oral cavity associated with health and disease, but these studies relied on reference genomes and did not capture strain-level variation or the native distribution of BGCs. Here, we assembled three independently sourced metagenomic datasets from healthy and dental caries samples, extracted BGCs and quantified their metagenomic abundance and transcriptional activity. We found that aryl polyene, ribosomally synthesized and posttranslationally modified peptide, and nonribosomal peptide encoding BGCs were the most prominent BGCs identified across the three metagenomic datasets. We grouped the identified BGCs into homology-based gene cluster families (GCFs) and found that specific GCFs were consistently associated with either health or caries across diverse taxa, suggesting that some specialized metabolites may perform conserved ecological functions. Conversely, other BGCs showed more restricted taxonomic distributions and were linked to disease-associated taxa, such as Propionibacterium acidifaciens, suggesting niche-specific biosynthetic capacities within the oral environment. Applying elastic-net regression to the metatranscriptomic dataset further identified a subset of 51 BGCs out >3,000 that distinguished healthy from caries samples, reinforcing the discriminatory power of BGC expression patterns. These results demonstrate that BGCs can provide functional resolution beyond taxonomic profiling and that BGC expression, rather than genomic presence alone, can differentiate oral microbial community states. This underscores the relevance of specialized metabolism to oral health and supports the use of BGC-centric analyses to interrogate microbial interactions underlying community stability and disease-associated shifts. One-sentence summary Specialized metabolites in oral bacteria are differentially expressed in healthy and cavity-affected communities.

  View details for DOI 10.1093/jimb/kuag005

  View details for Web of Science ID 001844908500001

  View details for PubMedID 41604220

  View details for PubMedCentralID PMC13455363

• Synergistic action of specialized metabolites from divergent biosynthesis in the human oral microbiome PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Yao, M., Zill, N. A., Barber, C., Du, Y., Lin, P., Zhai, R., Yoon, E., Al Marzooqi, D., Zhang, W. 2025; 122 (34): e2504492122

  Abstract

  Despite extensive efforts, our understanding of the virulence factors contributing to oral biofilm formation-a hallmark of dental caries-remains incomplete. We present evidence that the specialized metabolism of the oral microbiome is a critical yet underexplored factor in oral biofilm formation. Through microbiome analysis, we identified a hybrid nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) encoding biosynthetic gene cluster that correlates with dental caries and is widely represented in oral pathogens, including Streptococcus mutans. This gene cluster produces two major mutanoclumpin metabolites, MC-584 and MC-586, which feature molecular scaffolds differing in a C-C macrocyclic linkage. Both metabolites synergistically promote robust biofilm formation of S. mutans through a rare dual-metabolite mode of action. Further, each metabolite binds uniquely to the S. mutans cell surface, resulting in distinct multicellular morphologies. The biosynthesis of mutanoclumpins employs a unique chemical logic that produces two major products, rare within PKS-NRPS assembly lines. This study underscores the importance of characterizing genes implicated in human diseases through microbiome analysis and lays the foundation for exploring strategies to inhibit streptococci-induced dental caries.

  View details for DOI 10.1073/pnas.2504492122

  View details for Web of Science ID 001562202600001

  View details for PubMedID 40828023

  View details for PubMedCentralID PMC12403116

• Double emulsions as a high-throughput enrichment and isolation platform for slower-growing microbes. ISME communications McCully, A. L., Loop Yao, M., Brower, K. K., Fordyce, P. M., Spormann, A. M. 2023; 3 (1): 47

  Abstract

  Our understanding of in situ microbial physiology is primarily based on physiological characterization of fast-growing and readily-isolatable microbes. Microbial enrichments to obtain novel isolates with slower growth rates or physiologies adapted to low nutrient environments are plagued by intrinsic biases for fastest-growing species when using standard laboratory isolation protocols. New cultivation tools to minimize these biases and enrich for less well-studied taxa are needed. In this study, we developed a high-throughput bacterial enrichment platform based on single cell encapsulation and growth within double emulsions (GrowMiDE). We showed that GrowMiDE can cultivate many different microorganisms and enrich for underrepresented taxa that are never observed in traditional batch enrichments. For example, preventing dominance of the enrichment by fast-growing microbes due to nutrient privatization within the double emulsion droplets allowed cultivation of slower-growing Negativicutes and Methanobacteria from stool samples in rich media enrichment cultures. In competition experiments between growth rate and growth yield specialist strains, GrowMiDE enrichments prevented competition for shared nutrient pools and enriched for slower-growing but more efficient strains. Finally, we demonstrated the compatibility of GrowMiDE with commercial fluorescence-activated cell sorting (FACS) to obtain isolates from GrowMiDE enrichments. Together, GrowMiDE + DE-FACS is a promising new high-throughput enrichment platform that can be easily applied to diverse microbial enrichments or screens.

  View details for DOI 10.1038/s43705-023-00241-9

  View details for PubMedID 37160952