StrR-like Regulator HMM Model

Author: Sam Williams
Date: 06/03/2024

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Model Overview

This model is designed to identify StrR-like pathway-specific regulators (PSR). StrR-like regulators are known to play a role in the regulation of several clinically important natural product classes.

Natural Product Classes Regulated by StrR-like Regulators

• Glycopeptides: vancomycin, teicoplanin, balhimycin
• Aminoglycosides: streptomycin, kanamycin
• Aminocyclitols: spectinomycin
• Chloramphenicol

Model Creation

This HMM model was created from a list of 83 validated sequences, identified in the paper:
The Impact of Heterologous Regulatory Genes from Lipodepsipeptide Biosynthetic Gene Clusters on the Production of Teicoplanin and A40926.

• File Used: Multi-header file StrR_all_together.fasta

Model Validation

To check the validity of the model, a "leave-one-out analysis" was performed using the Leave_one_out_analysis.py script.

• Results File: master_hmmsearch_results.csv
• Score Range:
  • Highest: 467.7 (decaplanin)
  • Lowest: 312.8 (pyrazofurin)

Application to MiBIG 3.0 Database

The model was applied to the MiBIG 3.0 database using the following command:

hmmscan --tblout mibig_3.0_tbl_StrR_test.tbl --cpu 12 --noali --nobias StrR_model.hmm mibig_prot_seqs_3.1.fasta

• Summary of Results:
  • High-Scoring Hits:
    • Highest: 469.6 (vancomycin)
  • Low-Scoring Hits Examples:
    • Lowest: -12.9 (xenovulene A)
    • Low cut off: 207.7 (streptonigrin)

Suggested Cut-off based on bimodal distribution is 195

• Results File: mibig_3.0_hmmsearch_results.csv