Left: Predicted gene regulatory network of Streptomyces coelicolor based on 17 well-known regulators. Each node in the network represents a (regulatory) gene, and every edge represents a PWM predicted regulatory interaction between nodes. The edges colored in dark gray indicate strong PWM prediction scores, while the lighter gray shades represent weaker interactions. Matches within BGC regions are depicted as triangles. In six regions (black circled), the matches fall within a co-expressed region, highlighting their functional relation to these compounds. Right: Proposed biosynthetic pathway for assembly of desferrioxamines E and B. Main biosynthetic enzymes presented in bold face. DesG and DesH balance intracellular N-hydroxy-N-succinylcadaverine (HSC) and N-hydroxy-N-acetylcadaverine (HAC) concentrations by converting HSC to HAC. In the absence of DesG and/or DesH, the cells likely fail to produce sufficient levels of HAC, thereby strongly attenuating the production of DFOB. Although DesC has been shown to be able to catalyze the acetylation of N-hydroxycadaverine in vitro, the enzyme can only modestly compensate for the loss of DesH in vivo, underlining the important role played by DesG and DesH in DFOB production.

Most #biosynthetic gene clusters remain uncharacterized. @marnixmedema.bsky.social @gillesvanwezel.bsky.social &co integrate #GRN analysis & global expression data to identify desJGH as an operon essential for #biosynthesis of #desferrioxamineB in Streptomyces @plosbiology.org 🧪 plos.io/43UVUPB

Left: Predicted gene regulatory network of Streptomyces coelicolor based on 17 well-known regulators. Each node in the network represents a (regulatory) gene, and every edge represents a PWM predicted regulatory interaction between nodes. The edges colored in dark gray indicate strong PWM prediction scores, while the lighter gray shades represent weaker interactions. Matches within BGC regions are depicted as triangles. In six regions (black circled), the matches fall within a co-expressed region, highlighting their functional relation to these compounds. Right: Proposed biosynthetic pathway for assembly of desferrioxamines E and B. Main biosynthetic enzymes presented in bold face. DesG and DesH balance intracellular N-hydroxy-N-succinylcadaverine (HSC) and N-hydroxy-N-acetylcadaverine (HAC) concentrations by converting HSC to HAC. In the absence of DesG and/or DesH, the cells likely fail to produce sufficient levels of HAC, thereby strongly attenuating the production of DFOB. Although DesC has been shown to be able to catalyze the acetylation of N-hydroxycadaverine in vitro, the enzyme can only modestly compensate for the loss of DesH in vivo, underlining the important role played by DesG and DesH in DFOB production.

Most #biosynthetic gene clusters remain uncharacterized. @marnixmedema.bsky.social @gillesvanwezel.bsky.social &co integrate #GRN analysis & global expression data to identify desJGH as an operon essential for #biosynthesis of #desferrioxamineB in Streptomyces @plosbiology.org 🧪 plos.io/43UVUPB

Left: Predicted gene regulatory network of Streptomyces coelicolor based on 17 well-known regulators. Each node in the network represents a (regulatory) gene, and every edge represents a PWM predicted regulatory interaction between nodes. The edges colored in dark gray indicate strong PWM prediction scores, while the lighter gray shades represent weaker interactions. Matches within BGC regions are depicted as triangles. In six regions (black circled), the matches fall within a co-expressed region, highlighting their functional relation to these compounds. Right: Proposed biosynthetic pathway for assembly of desferrioxamines E and B. Main biosynthetic enzymes presented in bold face. DesG and DesH balance intracellular N-hydroxy-N-succinylcadaverine (HSC) and N-hydroxy-N-acetylcadaverine (HAC) concentrations by converting HSC to HAC. In the absence of DesG and/or DesH, the cells likely fail to produce sufficient levels of HAC, thereby strongly attenuating the production of DFOB. Although DesC has been shown to be able to catalyze the acetylation of N-hydroxycadaverine in vitro, the enzyme can only modestly compensate for the loss of DesH in vivo, underlining the important role played by DesG and DesH in DFOB production.

Most #biosynthetic gene clusters remain uncharacterized. @marnixmedema.bsky.social @gillesvanwezel.bsky.social &co integrate #GRN analysis & global expression data to identify desJGH as an operon essential for #biosynthesis of #desferrioxamineB in Streptomyces @plosbiology.org 🧪 plos.io/43UVUPB