Linaridins
and lanthipeptides are two classes of natural products
belonging to the ribosomally synthesized and posttranslationally modified
peptide (RiPP) superfamily. Although these two RiPP classes share
similar structural motifs such as dehydroamino acids and thioether-based
cross-links, the biosynthesis of linaridins and lanthipeptides involved
distinct sets of enzymes. Here, we report the identification of a
novel lanthipeptide cypepeptin from a recombinant strain of Streptomyces lividans, which harbors most of the
cypemycin (a prototypic linaridin) biosynthetic gene cluster but lacks
the decarboxylase gene cypD. In contrast to the generally
believed structure of cypemycin, multiple d-amino acids and
Z-dehydrobutyrines were observed in both cypepeptin and cypemycin,
and the stereochemistry of each amino acid was established by the
extensive structural analysis in combination with genetic knockout
and mutagenesis studies. Comparative analysis of cypemycin and cypepeptin
showed that the aminovinyl-cysteine (AviCys) moiety of cypemycin plays
an essential role in disrupting the cell integrity of M. luteus, which cannot be functionally substituted
by the structurally similar lanthionine moiety.
Glyphosate is a widely used herbicide with an annual production of more than one million tons globally. Current commercialized production processes of glyphosate are generally associated with manufacturing hazards and toxic wastes. Recently, many countries have strengthened environmental supervision and law enforcement on glyphosate manufacturing. Therefore, a green source of glyphosate is required. Here, we characterize the genes required for producing aminomethylphosphonate (AMP), one of the intermediates in the biosynthesis of the potent antibiotics argolaphos. We apply a synthetic biology strategy to improve AMP production in Streptomyces lividans, with fermentation titers of 52 mg L-1, a 500-fold improvement over the original strain. Furthermore, we develop an efficient and practical chemical process for converting AMP to glyphosate. Our findings highlight one greenness-driven alternative in the production of glyphosate.
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