Systems and Methods for Identifying and Expressing Gene Clusters

Abstract

Methods for identifying biosynthetic gene clusters that include genes for producing compounds that interact with specific target proteins are disclosed. Some methods relate to bioinformatics methods for identifying and/or prioritizing biosynthetic gene clusters. Related systems, components, and tools for the identification and expression of such gene clusters are also disclosed.

What is claimed is: 
     
         1 . A system for identifying one or more candidate biosynthetic gene cluster for introduction into a host organism to produce one or more compounds that modulate a specific non-fungal target protein, the system comprising:
 a processor; and   a memory containing a gene cluster identification application;
 wherein the gene cluster identification application directs the processor to: 
 load data describing at least one target protein into the memory; 
 load data describing a plurality of biosynthetic gene clusters into the memory; 
 score each of the plurality of biosynthetic gene clusters based on:
 the presence of one or more homologs of a target protein within or adjacent to the biosynthetic gene cluster, as determined by a homology search; and 
 the confidence in homology of the target protein to genes in the biosynthetic gene cluster. 
 
   
     
     
         2 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is further based on a fraction of a gene encoding a homolog of the target protein that meets a certain threshold of identity, wherein the certain threshold of identify is at least 25%. 
     
     
         3 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is further based on a total number of genes homologous to the target protein present in an entire genome of the organism. 
     
     
         4 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is further based on a phylogenetic relationship of the target protein to the one or more homologs of the target protein in or adjacent the biosynthetic gene cluster. 
     
     
         5 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is further based on an expected number of the one or more homologs of the target protein in or adjacent to the biosynthetic cluster. 
     
     
         6 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is further based on a likelihood that the target protein is essential for viability, growth, or other cellular processes in a native environment. 
     
     
         7 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is further based on synteny of the biosynthetic gene cluster with related species. 
     
     
         8 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is further based on whether a gene of the biosynthetic gene cluster that encodes a protein is within a protein class that is known to be targeted by secondary metabolites. 
     
     
         9 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is further based on a presence of one or more specific promoters adjacent to the one or more homologs of the target protein. 
     
     
         10 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is further based on a presence of specific regulatory elements in the biosynthetic gene cluster. 
     
     
         11 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is further based on a presence of the one or more homologs of the target protein outside the biosynthetic gene cluster that are co-regulated with some or all of the genes in the biosynthetic cluster. 
     
     
         12 . The method of  claim 1 , wherein the score for each of the plurality of biosynthetic gene clusters is based on a presence of protein- and DNA-sequence-derived features within the biosynthetic gene cluster that are known to produce secondary metabolites. 
     
     
         13 . The method of  claim 1 , wherein the target protein is not from a species from which any of the gene clusters originate.