Biosynthesis, regulation, and engineering of natural products from Lysobacter

Abstract

This review summarizes progress in Lysobacter natural product research over the past 10 years, including identification, mechanisms for biosynthesis and regulation, and metabolic engineering.

Underexplored bacteria as reservoirs of novel antimicrobial lipopeptides

“…Recently, new analogues of WAP-8294A were identified (AZ1–AZ4, AZ6, and AZ7) from a L. enzymogenes OH11 strain, where the structures differed from A2 in one amino acid residue or the length of the fatty acid chain ( Zhu et al, 2022 ). Due to its potent antimicrobial activity against MRSA, WAP-8294A2 (also referred to as Lotilibcin) underwent phase I/II clinical trials by aRigen Pharmaceuticals in 2009 ( Gómez Expósito et al, 2015 ; Yue et al, 2022 ). Currently, stage II clinical trials, for the topical application treatment of Gram-positive bacterial infections, are underway ( Dijksteel et al, 2021 ).…”

“…The peptide structure of this compound is comprised of Val-Arg-Ser-Gly-( N me-Phe)-Leu-Arg-Glu-Val-Trp-Aba (where Aba refers to aminobutyric acid) ( Figure 3C ). This compound also exhibited strong antimicrobial activity against MRSA (MICs of 0.25–2 μg/ml) and Staphylococcus epidermis (MIC ≤0.25 μg/ml) ( Yue et al, 2022 ).…”

“…The primary cyclic lipodepsipeptide identified in this family was named lysocin E and has a peptide moiety of 12 amino acid residues [Thr-Arg-Ser-Gly-( N me-Phe)-Leu-Arg-Glu-Gln-Trp-Ile-Thr], with an ester linkage to the fatty acid chain (3-OH-5-Me-hexanoic acid) ( Figure 3C ) ( Hamamoto et al, 2015 ). Although similar in their amino acid sequence to other cyclic lipopeptides such as WAP-8294A2 and WBP-29479A1, the fatty acid of the lysocins does not form part of the cyclic system ( Yue et al, 2022 ). Derivatives of lysocins (A–I) have been shown to differ in the length of the fatty acid chain, and in the methylation of Phe in the fifth position Panthee et al (2016) .…”

“…Several derivatives of tripropeptin have been identified, each differing in the length of the fatty acid chain ( Hashizume et al, 2011 ). Tripropeptin C is reported to exhibit the most potent antimicrobial activity against MRSA, penicillin-resistant Streptococcus pneumoniae and VRE ( Arlt et al, 2021 ; Yue et al, 2022 ).…”

“…Predatory bacteria have also been recognised as natural factories of bioactive compounds, as their lifestyle depends on the production of various enzymes and secondary metabolites to naturally invade and consume specific prey microorganisms as a nutrient source ( Rosenberg and Varon, 1984 ; Herencias et al, 2020 ; Sester et al, 2020 ; Atterbury and Tyson, 2021 ). Certain predatory bacterial genera, such as such as Myxococcus , Cystobacter, and Lysobacter , have then been identified to produce lipopeptides during secondary metabolism ( Herrmann et al, 2017 ; Yan et al, 2018 ; Yue et al, 2022 ). For example, one of the most extensively studied lipopeptides produced by Myxococcus species [including Myxococcus virescens ( M. virescens ) , Myxococcus xanthus ( M. xanthus ) and an unclassified Myxococcus sp.…”