Abstract
Secondary metabolites (SM) produced by fungi and bacteria have long been of exceptional interest owing to their unique biomedical ramifications. The traditional discovery of new natural products that was mainly driven by bioactivity screening has now experienced a fresh new approach in the form of genome mining. Several bioinformatics tools have been continuously developed to detect potential biosynthetic gene clusters (BGCs) that are responsible for the production of SM. Although the principles underlying the computation of these tools have been discussed, the biological background is left underrated and ambiguous. In this review, we emphasize the biological hypotheses in BGC formation driven from the observations across genomes in bacteria and fungi, and provide a comprehensive list of updated algorithms/tools exclusively for BGC detection. Our review points to a direction that the biological hypotheses should be systematically incorporated into the BGC prediction and assist the prioritization of candidate BGC.
Highlights
Fungi and bacteria produce a plethora of bioactive secondary metabolites (SMs), many of which play vital roles in medicine, such as antibiotics and anticancer reagents
We mainly focus on the biological background of biosynthetic gene clusters (BGCs) prioritization to complement most similar reviews in computation of identifying BGC or the resistance hypothesis only
With a traditional approach, granaticin was first isolated from Streptomyces olivaceus in 1957 and detected in S. violaceoruber based on antimicrobial testing against Gram-positive bacteria and protozoa (Barcza et al 1966; Carbaz et al 1957)
Summary
Fungi and bacteria produce a plethora of bioactive secondary metabolites (SMs), many of which play vital roles in medicine, such as antibiotics and anticancer reagents. The biological foundation of current target-directed BGC prioritization was mainly derived from observations in Salinispora species While this lineage represents a large proportion of natural product producers, it certainly does not account for the diversity in nature. The number of duplicates raises certain doubts about the predictability of potential BGCs. Theoretically, a single copy of the essential gene is sufficient to protect the producers, which has been observed in many species (Kale et al 2011; Thiara and Cundliffe 1989). There are some cases of interkingdom HGT, such as the ancient transfer event of 6-methylsalicylic acid-type PKS from actinobacteria to ascomycete fungi (Schmitt and Lumbsch 2009; Sieber et al 2014)
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