Erratum: The dabABC operon is a marker of C4-alkylated monobactam biosynthesis and responsible for (2S,3R)-diaminobutyrate production.

[This corrects the article DOI: 10.1016/j.isci.

The operon is a marker of C4-alkylated monobactam biosynthesis and responsible for (,)-diaminobutyrate production.

Non-ribosomal peptide synthetases (NRPSs) assemble metabolites of medicinal and commercial value. Both serine and threonine figure prominently in these processes and separately can be converted to the additional NRPS building blocks 2,3-diaminopropionate (Dap) and 2,3-diaminobutyrate (Dab). Here we bring extensive bioinformatics, and experimentation to compose a unified view of the biosynthesis of these widely distributed non-canonical amino acids that both derive by pyridoxal-mediated β-elimination of the activated -phosphorylated substrates followed by β-addition of an amine donor.

Synthesis of functionalized 2,3-diaminopropionates and their potential for directed monobactam biosynthesis.

The -sulfonated monobactams harbor considerable potential to combat emerging bacterial infections that are problematic to treat due to their metallo-β-lactamase mediated resistance against conventional β-lactam antibiotics. Herein, we report a divergent synthesis of C3-substituted 2,3-diaminopropionates featuring an array of small functional groups and examine their potential as alternative precursors during monobactam biosynthesis in a mutant strain () of that is deficient in the supply of this native precursor. assays revealed high diastereoselectivity, as well as a substrate tolerance by the terminal adenylation domain of the non-ribosomal peptide synthetase (NRPS) SulM toward the majority of synthetic analogs.

Colorimetric Determination of Adenylation Domain Activity in Nonribosomal Peptide Synthetases by Using Chrome Azurol S.

Adenylation domains are the main contributor to structural complexity among nonribosomal peptides due to their varied but stringent substrate selection. Several in vitro assays to determine the substrate specificity of these dedicated biocatalysts have been implemented, but high sensitivity is often accompanied by the cost of laborious procedures, expensive reagents or the requirement for auxiliary enzymes. Here, we describe a simple protocol that is based on the removal of ferric iron from a preformed chromogenic complex between ferric iron and Chrome Azurol S.

Early Oxidative Transformations During the Biosynthesis of Terrein and Related Natural Products.

The mycotoxin terrein is derived from the C -precursor 6-hydroxymellein (6-HM) via an oxidative ring contraction. Although the corresponding biosynthetic gene cluster (BGC) has been identified, details of the enzymatic oxidative transformations are lacking. Combining heterologous expression and in vitro studies we show that the flavin-dependent monooxygenase (FMO) TerC catalyzes the initial oxidative decarboxylation of 6-HM.

Co-Oxidative Transformation of Piperine to Piperonal and 3,4-Methylenedioxycinnamaldehyde by a Lipoxygenase from Pleurotus sapidus.

The valuable aroma compound piperonal with its vanilla-like olfactory properties is of high interest for the fragrance and flavor industry. A lipoxygenase (LOX 1) of the basidiomycete Pleurotus sapidus was identified to convert piperine, the abundant pungent principle of black pepper (Piper nigrum), to piperonal and a second volatile product, 3,4-methylenedioxycinnamaldehyde, with a vanilla-like odor through an alkene cleavage. The reaction principle was co-oxidation, as proven by its dependence on the presence of linoleic or α-linolenic acid, common substrates of lipoxygenases.

Biosynthesis of 6-Hydroxymellein Requires a Collaborating Polyketide Synthase-like Enzyme.

The polyketide synthase (PKS)-like protein TerB, consisting of inactive dehydratase, inactive C-methyltransferase, and functional ketoreductase domains collaborates with the iterative non reducing PKS TerA to produce 6-hydroxymellein, a key pathway intermediate during the biosynthesis of various fungal natural products. The catalytically inactive dehydratase domain of TerB appears to mediate productive interactions with TerA, demonstrating a new mode of trans-interaction between iterative PKS components.

The same but different: multiple functions of the fungal flavin dependent monooxygenase SorD from Penicillium chrysogenum.

Sorbicillinoids are a large family of fungal secondary metabolites with a diverse range of structures and numerous bioactivites, some of which have pharmaceutical potential. The flavin-dependent monooxygenase SorD from Penicillium chrysogenum (PcSorD) utilizes sorbicillinol to catalyze a broad scope of reactions: formation of oxosorbicillinol and epoxysorbicillinol; intermolecular Diels-Alder and Michael-addition dimerization reactions; and dimerization of a sorbicillinol derivative with oxosorbicillinol. PcSorD shares only 18.

Diels-Alder Reactions During the Biosynthesis of Sorbicillinoids.

The sorbicillinoids are a class of biologically active and structurally diverse fungal polyketides arising from sorbicillin. Through co-expression of sorA, sorB, sorC, and sorD from Trichoderma reesei QM6a, the biosynthetic pathway to epoxysorbicillinol and dimeric sorbicillinoids, which resemble Diels-Alder-like and Michael-addition-like products, was reconstituted in Aspergillus oryzae NSAR1. Expression and feeding experiments demonstrated the crucial requirement of the flavin-dependent monooxygenase SorD for the formation of dimeric sorbicillinoids, hybrid sorbicillinoids, and epoxysorbicillinol in vivo.