SolS-catalyzed sulfoxidation of labionin to solabionin drives antibacterial activity of solabiomycins.

Shinta Ijichi, Shotaro Hoshino, Shumpei Asamizu, Hiroyasu Onaka

Bioorganic & medicinal chemistry letters 2023 Jun 01

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Ribosomally synthesized and posttranslationally modified peptides (RiPPs) with polar-functionalized fatty acyl groups are newly found lipopeptide-class natural products. We recently employed a combined approach of genome mining and stable isotope labeling and discovered solabiomycins as one of the polar-functionalized fatty-acylated RiPPs (PFARs) from Streptomyces lydicus NBRC13058. The solabiomycins contained a characteristic sulfoxide group in the labionin moiety referred to as the 'solabionin' structure for the RiPP moiety. A previous gene knockout experiment indicated that solS, which encodes a putative flavin adenine dinucleotide (FAD)-nicotinamide adenine dinucleotide (phosphate) (NAD(P))-binding protein, is involved in the sulfoxidation of an alkyl sulfide in the solabionin. In this study, we isolated deoxysolabiomycins A and B from ΔsolS mutant and fully determined the chemical structures using a series of NMR experiments. We also tested the bioactivity of deoxysolabiomycins against Gram-positive bacteria, including Mycolicibacterium smegmatis, and notably found that the sulfoxide is critical for the antibacterial activity. To characterize the catalytic activity of SolS, the recombinant protein was incubated with a putative substrate, deoxysolabiomycins, and the cofactors FAD and NADPH. In vitro reactions demonstrated that SolS catalyzes the sulfoxidation, converting deoxysolabiomycins to solabiomycins. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Shinta Ijichi, Shotaro Hoshino, Shumpei Asamizu, Hiroyasu Onaka. SolS-catalyzed sulfoxidation of labionin to solabionin drives antibacterial activity of solabiomycins. Bioorganic & medicinal chemistry letters. 2023 Jun 01;89:129323