Natural-product discovery

Taxonomy- and metabolite-aware microbial library prioritization with IDBac

A microbial natural-product discovery strategy that combines MALDI protein fingerprinting with specialized-metabolite overlap to reduce taxonomic and chemical redundancy when constructing or downsizing isolate libraries.

Journal of Natural Products · 2019 · 10.1021/acs.jnatprod.9b00168

MALDI-MSMetabolite profilingNatural-product discovery

What does this strategy enable?

This strategy uses two complementary MALDI information spaces before scale-up. Protein-region spectra group bacterial isolates by taxonomic or strain-level similarity, while lower-mass specialized-metabolite spectra reveal chemical overlap within those groups. Isolates can then be selected to preserve phylogenetic breadth while minimizing redundant natural-product profiles, shifting strain prioritization from morphology or taxonomy alone to combined biological and chemical evidence.

Transferable workflow

Workflow

  1. 1

    Acquire MALDI protein fingerprints from individual isolates

    Analyze colony material in the higher mass range to generate replicate protein fingerprints suitable for similarity grouping.

  2. 2

    Group taxonomically similar isolates

    Use protein-profile clustering to organize the collection into operational groups of closely related isolates.

  3. 3

    Acquire specialized-metabolite profiles

    Analyze the lower mass region from the same isolate collection to capture differences in specialized-metabolite production.

  4. 4

    Compare chemical overlap within taxonomic groups

    Use metabolite association patterns to identify isolates that add distinct chemistry rather than duplicating existing profiles.

  5. 5

    Select a reduced but diverse library

    Prioritize representatives that retain taxonomic breadth and specialized-metabolite diversity for fermentation, extraction, and downstream discovery.

Connected resources

Tools used in this strategy

Strategy profile

Related objectives

Phenotype association

Components

Sample preparation, Data acquisition, Preprocessing and feature extraction, Metadata analysis, Statistical analysis, Biological validation

Sample types

Microbial culture or biomass

Biological context

Microbial

Ion mobility

Ion mobility not required

Scope and considerations

Designed for

  • Building or reducing bacterial isolate libraries for natural-product discovery.
  • Prioritizing isolates before scale-up using both relatedness and chemical phenotype.

Important requirements

  • Cultured bacterial isolates and reproducible MALDI protein and small-molecule acquisitions.

Considerations

  • Culture conditions strongly influence specialized-metabolite profiles, so observed chemical redundancy is condition-dependent.
  • Protein spectral similarity is an operational grouping method and does not replace sequence-based taxonomy when definitive identification is required.

Reusable resources

✓ Published method available

Publication

Costa MS, Clark CM, Ómarsdóttir S, Sanchez LM, Murphy BT. Minimizing Taxonomic and Natural Product Redundancy in Microbial Libraries Using MALDI-TOF MS and the Bioinformatics Pipeline IDBac. Journal of Natural Products 82, 2167–2173 (2019).

doi:10.1021/acs.jnatprod.9b00168