Enhanced Triacylglycerol Metabolism Contributes to Efficient Oil Utilization and High-Level Production of Salinomycin in Streptomyces albus ZD11

Abstract

Streptomyces is well-known for biosynthesis of secondary metabolites with diverse bioactivities. Although oils have been employed as carbon sources to produce polyketide antibiotics for several industrial Streptomyces strains, the intrinsic correlation between oil utilization and high production of antibiotics still remains unclear. In this study, we investigate the correlation between oil metabolism and salinomycin biosynthesis in Streptomyces albus ZD11 which employs soybean oil as the main carbon source. Comparative genomic analysis revealed the enrichment of genes related to triacylglycerol (TAG) metabolism in S. albus ZD11. Transcriptomic profiling further confirmed the enhancement of TAG metabolism and acyl-coenzyme A biosynthesis in S. albus ZD11. Multiple secreted lipases, which catalyze the TAG hydrolysis, were seen to be working in a synergistic and complementary manner in aiding the efficient and stable hydrolyzation of TAGs. Together, our study suggests that enhanced TAG hydrolysis and fatty acid degradation contribute to the high-efficientcy of oil utilization in S. albus ZD11 in order to provide abundant carbon precursors for cell growth and salinomycin biosynthesis. Importance In order to obtain a high production of antibiotics, oils have been used as the main carbon source for some Streptomyces strains. Based on multi-omics analysis, this study provides insight into the relationship between triacylglycerol (TAG) metabolism and antibiotic biosynthesis in S. albus ZD11, an oil-preferring industrial Streptomyces strain. Our investigation into TAG hydrolysis gave the further evidence that this strain utilized complicated strategies enabling an efficient TAG metabolism. In addition, a novel secreted lipase was identified that exhibited highly hydrolytic activity towards medium- and long-chain TAGs. Our finding presents a good start to clarify the complicated relationship between TAG catabolism and high antibiotic production in the industrial strains.

An Efficient Markerless Deletion System Suitable for the Industrial Strains of Streptomyces

“…Moreover, S. albus ZD11, S. coeruleorubidus, and their derivative strains were grown on ISP4 agar medium (BD, USA) for 6-7 days at 30 o C for sporulation. Tryptic Soy Broth (TSB) medium (3% TSB) was used for pre-cultivation [18]. The yield of salinomycin was determined as described previously [18].…”

“…Tryptic Soy Broth (TSB) medium (3% TSB) was used for pre-cultivation [18]. The yield of salinomycin was determined as described previously [18]. To determine the production of daunorubicin, the fermentation broth was hydrolyzed by treatment with 39.2 mg of oxalic acid dihydrate per ml at 50 o C for 60 min and then mixed with anhydrous methanol at the ratio of 1:9 for 12 h at room temperature.…”

Establishing an efficient salinomycin biosynthetic pathway in three heterologous Streptomyces hosts by constructing a 106‐kb multioperon artificial gene cluster

“…We posit that the highly productive salinomycin biosynthetic pathway imposes a burden on the host and may impair cell division by affecting primary metabolism. We aim to elucidate the Biosynthesis of the salinomycin polyketide skeleton requires malonyl-CoA, methylmalonyl-CoA, and ethylmalonyl-CoA as building blocks, which can be provided by the efficient β-oxidation of fatty acids in the oil-rich medium (Li et al, 2020;Lu et al, 2016). Recently, the "dynamic degradation of triacylglycerol" (ddTAG) strategy was developed to channel carbon flux into polyketide biosynthesis by fine-tuning the expression of the ACS gene involved in the first step of β-oxidation (Wang et al, 2020).…”

“…These genes enable DSM41398 to efficiently consume soybean oil to provide abundant carbon substrates for cell growth and salinomycin biosynthesis (Li et al, 2020).…”

“…Another potential reason for the lower productivity of the three heterologous hosts used in this study is that the number of genes involved in triacylglycerol catabolism in their genomes is significantly less abundant than that in DSM41398 (Li et al, 2020;Lu et al, 2016).…”