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submitted on 31.08.2020 and posted on 01.09.2020by Neil L Grenade, Dragos S. Chiriac, Graeme W. Howe, Avena Ross
Bacterial natural products are an immensely valuable source of therapeutics. As modern DNA sequencing efforts provide
increasing numbers of microbial genomes, it is clear that the molecules produced by most natural product biosynthetic gene
clusters (BGCs) remain unknown. Genome mining makes use of bioinformatic techniques to elucidate the natural products
produced by these “orphan” BGCs. Here, we report the use of sequence similarity networks (SSNs) and genome
neighborhood networks (GNNs) to identify an orphan BGC that is responsible for the production of the antitumor
tambjamine BE-18591 in Streptomyces albus NRRL B-2362. Although BE-18591 is a close structural analogue of tambjamine
YP1 produced by Pseudoalteromonas tunicata, the biosynthetic routes to produce these molecules differ significantly.
Notably, the C12-alkylamine tail that is appended onto the bipyrrole core of tambjamine YP1 is derived from fatty acids
siphoned from the primary metabolism of the pseudoalteromonad, whilst the S. albus NRRL B-2362 BGC encodes a dedicated
system for the de novo biosynthesis of the alkylamine portion of tambjamine BE-18591. These remarkably different
biosynthetic strategies represent a striking example of convergent BGC evolution, with selective pressure for the production
of tambjamines seemingly leading to the emergence of separate biosynthetic pathways in pseudoalteromonads and
streptomycetes that ultimately produce closely related compounds