Abstract
Ohmyungsamycins (OMSs) A and B are cyclic depsipeptides produced by marine Streptomyces strains, which are synthesized by a non-ribosomal peptide synthetase. Notably, OMS A exhibits more potent activity against Mycobacterium tuberculosis and human cancer cells than OMS B. The substrate promiscuous adenylation (A) domain in the second module of OMS synthetase recruits either L-Val or L-Ile to synthesize OMSs A and B, respectively. Engineering of the substrate-coding residues of this A domain increased OMS A production by 1.2-fold, coupled with a drastic decrease in OMS B production. Furthermore, the culture conditions (sea salt concentration, inoculum size, and the supply of amino acids to serve as building blocks for OMS) were optimized for OMS production in the wild-type strain. Finally, cultivation of the A2-domain-engineered strain under the optimized culture conditions resulted in up to 3.8-fold increases in OMS A yields and an 8.4-fold decrease in OMS B production compared to the wild-type strain under the initial culture conditions.
Highlights
Ohmyungsamycins (OMSs) are macrocyclic peptides with antibacterial and anticancer properties, which are produced by marine bacterial strains belonging to the Streptomyces genus (Um et al, 2013; Kim et al, 2017; Byun et al, 2020)
A recent study (Kim et al, 2019) reported that OMSs are biosynthesized by the OhmA encoding non-ribosomal peptide synthetase (NRPS), which is comprised of 12 modules (Figure 1)
Escherichia coli DH5α was used as the host for general cloning, and non-methylating E. coli ET12567/pUZ8002 was used for conjugal transfer of recombinant plasmids between E. coli and Streptomyces (Kieser et al, 2000)
Summary
Ohmyungsamycins (OMSs) are macrocyclic peptides with antibacterial and anticancer properties, which are produced by marine bacterial strains belonging to the Streptomyces genus (Um et al, 2013; Kim et al, 2017; Byun et al, 2020). A recent study (Kim et al, 2019) reported that OMSs are biosynthesized by the OhmA encoding non-ribosomal peptide synthetase (NRPS), which is comprised of 12 modules (Figure 1). During the OMS biosynthesis process, the second A (A2) domain in module 2, which exhibits relaxed substrate selectivity, activates both L-Val and L-Ile to produce OMS A and OMS B, respectively.
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