Armeniaspirol Antibiotic Biosynthesis: Chlorination and Oxidative Dechlorination Steps Affording Spiro[4.4]non‐8‐ene

Abstract

Armeniaspirols are potent antibiotics containing an unusual spiro[4.4]non‐8‐ene moiety. Herein, we describe the cloning and functional analysis of the armeniaspirol biosynthetic gene cluster. Gene‐inactivation studies and subsequent isolation of previously unknown biosynthetic intermediates shed light on intriguing biosynthetic details. Remarkably, deletion of ams15, which encodes a protein bearing a flavin‐binding domain, led to the accumulation of several non‐spiro intermediates with various numbers of chlorine substitutions on the pyrrole moiety. The di‐ and trichloropyrrole species were converted by Streptomyces albus expressing Ams15 into mono‐ and dichlorinated spiro derivatives, respectively. In addition, in vitro conversion of these non‐spiro intermediates into des‐N‐methyl spiro intermediates by the cell lysate of the same recombinant strain proved Ams15 to be responsible for spiro formation through oxidative dehalogenation.

Molecular Mechanisms of Antibiotic Resistance and Novel Treatment Strategies for Helicobacter pylori Infections

“…pylori [ 68 ]. Armeniaspirols are antibiotics containing an unusual spiro(4.4)non-8-ene moiety bio-synthesized by Streptomyces armeniacus [ 69 ]. The compound has membrane-disrupting properties, which ultimately lead to an inhibition of biofilm formation.…”

A Permissive Medium Chain Acyl-CoA Carboxylase Enables the Efficient Biosynthesis of Extender Units for Engineering Polyketide Carbon Scaffolds

“…Armeniaspirols (ARMs; Figure ) are a small group of polyketide-type antibiotics effective against multidrug-resistant Gram-positive bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). , During in vivo biosynthesis, the structural variations in the C 6 position of ARMs ( ARM-1 to ARM-3 ) are derived from the incorporation of different medium chain length extender units, e.g., hexylmalonyl-CoA. , Instead of having a CCRC-encoding gene generally responsible for providing atypical extender units, the arm biosynthetic gene cluster contains two genes encoding a β-subunit ( arm13 ) and one ε-subunit ( arm14 ) of ACCase. Arm13 is both homologous to the medium chain-specific β-subunit MccB (61% identity) and the typical β-subunit of PCC (PccB) from Streptomyces coelicolor (63% identity).…”

Development of Integrated Vectors with Strong Constitutive Promoters for High-Yield Antibiotic Production in Mangrove-Derived Streptomyces

“…S. armeniacus DSM 43125 has been found to biosynthesize armeniaspirols, which are potent antibiotics against Gram-positive bacteria [4,22,23]. In S. armeniacus DSM 43125, SCO5768p and kasOp* show the best performances with kanamycin resistance up to 2200 µg/mL.…”