Abstract
Streptomyces sp. NP10 was previously shown to synthesize large amounts of free fatty acids (FFAs). In this work, we report the first insights into the biosynthesis of these fatty acids (FAs) gained after genome sequencing and identification of the genes involved. Analysis of the Streptomyces sp. NP10 draft genome revealed that it is closely related to several strains of Streptomyces griseus. Comparative analyses of secondary metabolite biosynthetic gene clusters, as well as those presumably involved in FA biosynthesis, allowed identification of an unusual cluster C12-2, which could be identified in only one other S. griseus-related streptomycete. To prove the involvement of identified cluster in FFA biosynthesis, one of its three ketosynthase genes was insertionally inactivated to generate mutant strain mNP10. Accumulation of FFAs in mNP10 was almost completely abolished, reaching less than 0.01% compared to the wild-type strain. Cloning and transfer of the C12-2 cluster to the mNP10 mutant partially restored FFA production, albeit to a low level. The discovery of this rare FFA biosynthesis cluster opens possibilities for detailed characterization of the roles of individual genes and their products in the biosynthesis of FFAs in NP10.
Highlights
Soil dwelling bacteria of the genus Streptomyces are well known for their ability to produce chemically diverse secondary metabolites (SMs)
Using Joint Genomics Institute online tools, we compared the genomes of NP10 and XylebKG-1, and found them to have a high degree of synteny (Figure 1A)
Based on the analyses described in the previous section, C12-2 was the only biosynthetic gene cluster (BGC) that we could presume to be responsible for production of high amounts of various, non-canonical free fatty acids (FFAs) accumulated by Streptomyces sp
Summary
Soil dwelling bacteria of the genus Streptomyces are well known for their ability to produce chemically diverse secondary metabolites (SMs) This genus, owing to its remarkable biosynthetic potential, is solely is responsible for originating about half of the antibiotics in today’s clinical use, not mentioning other bioactive molecules – anticancer agents, antifungals, biocontrol agents, and immunosuppressors (Chater, 2016). These compounds are SMs which, unlike components of the primary metabolism, such as amino acids, nucleotides, lipids, and carbohydrates, are not essential for the growth of Streptomyces bacteria. The pathway for the biosynthesis of common FAs in Streptomyces is rather well understood (Gago et al, 2011), details on the biosynthetic pathways for complex branched FAs are still missing
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