Elucidation of the Tailoring Steps in Julichrome Biosynthesis by Marine Gastropod Mollusk-Associated Streptomyces sampsonii SCSIO 054

Abstract

The biosynthetic gene cluster governing the production of antibacterial julichromes was identified from marine gastropod mollusk-associated Streptomyces sampsonii SCSIO 054. Post-PKS assembly/tailoring enzymes JuiL, JuiM, JuiI, and JuiN represent key assembly enzymes. JuiL serves as a ketoreductase. JuiM is an acetyltransferase. JuiI carries out an intriguing biaryl coupling of two julichrome Q 6 units (immediate JuiL, JuiM product) to afford julichrome Q 6−6 . JuiN carries out tailoring steps on julichrome Q 6−6 , transforming Q 6−6 into Q 3−3 .

Insights into the Multisymmetric Tailoring of Julichrome Compounds by the Oxygenases JuiN and JuiO: Enzymatic Processing around the Biaryl C–C Axis

“…The mass (m/z 701.1 [M − H] − ) and the max UV absorption (281 nm) of 4 were consistent with those of julichrome Q 6-8 , a species characterized by a hydroquinone group on only one side of the dimer (Figures 2c and S23). These results clearly indicated that JuiN hydroxylated julichrome Q 6-6 (3) at C10 and C10′ in a stepwise fashion to afford julichromes Q 6-8 (4) and Q 8-8 (5).…”

“…According to the coordinates of NADP + and 7-oxo-SD8, the binding orientation of NAD(P)H and julichrome Q 8-8 (5) was proposed. This provides us the basis to propose a putative mechanism of C9 carbonyl reduction for JuiO.…”

“… − Numerous examples have established that biaryl C–C coupling is the key biosynthetic step associated with the biological activities of biaryl-containing NPs. For instance, the symmetric homodimers of julichrome, himastatin, chloptosin, and recently discovered petrichorin all display biological activities superior to those of their respective monomeric units. The tailoring steps leading up to biaryl coupling chemistry have been systematically studied in many organisms; compounds of interest have included gossypol, sporandol, rufoschweintzin, nigerone, viriditoxin, himastatin, , and julichrome .…”

Marine Bacterial Secondary Metabolites: A Treasure House for Structurally Unique and Effective Antimicrobial Compounds

“…It has antibacterial properties against S. aureus and E. faecalis, with MIC values of 12 and 8 µM, respectively [225]. S. sampsonii SCSIO 054 is a marine-gastropodmollusk-associated bacteria with a biosynthetic gene cluster that governs the synthesis of the antibacterial compound julichromes [226]. The Hawaiian bobtail squid contains symbiotic bacterial consortia in the auxiliary nidamental gland (a female reproductive system that shields eggs from fouling microorganisms).…”

Discovery and Biosynthesis of the Amodesmycins, Aromatic Polyketide-Siderophore Hybrid Conjugates

“…Furthermore, the following post-tailoring modification reactions composed of redox, group transfer, hydrolysis, and rearrangement proceed to endow the diversity of structures in aromatic polyketides . Cytochrome P450 enzymes (P450s) that catalyze various oxidation reactions including hydroxylation, , epoxidation, and biaryl coupling, , are usually widely distributed in the post-tailoring modification process of natural product biosynthesis, but are seldom involved in the PKSII system . Here, we identified a type II polyketide biosynthetic gene cluster (BGC) amd (Genbank accession number OP356209) on a cosmid (ZF484) containing a 27.75-kb inserted eDNA from a soil metagenomic library, and obtained two novel benz­[ h ]­isoquinoline-desferrioxamine B hybrid compounds that we name amodesmycins ( 1 – 2 ) and a novel benz­[ h ]­isoquinoline derivative ( 3 ) by heterologous expression of a Streptomyces albus J1074 strain harboring the amd cluster ( S. albus / amd ).…”