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.

Dashuigou, a unique tellurium-dominated deposit over the world, is located in the western margin of the Yangtze craton in southwestern China. It is characterized by high-grade tellurium accompanied by bismuth, gold, silver, and sulfur, and occurs in the area of less than one km 2 . The mineralization is divided into three stages, i.e. (1) The data implies that these vein carbonates were formed by the mixing fluids of magmatic or mantle source with meteoric or formation water. The δ 18 O values of ore-forming fluids responsible for the formation of vein quartz are estimated to be +3.2 to +6.8, the δD values of inclusion fluids of the quartz are measured to be -54 to -82 per mil. All those stable isotopic data suggest the involvement of the fluids from mantle and/or mantle-derived magmas through fault system in the forming process of the Dashuigou tellurium deposit.

Industrial natamycin producing strain CGMCC 2644 S. chattanoogensis L10/ pINT01 L10 carrying vector pINT01, apr This study S. chattanoogensis L10/ pSOK804 L10 carrying vector pSOK804, apr This study S. chattanoogensis L10-Δazo L10 with disruption of azoxymycin BGC This study S. albus ZD11 A derivative obtained with streak plate method from an industrial salinomycin-producing strain CGMCC 4.7658 S. albus ZD11-Δsal ZD11 with disruption of salinomycin BGC This study S. albus ZD11-Δ200k ZD11 with disruption of 200 kb non-essential chromosomal region deleted This study S. coeruleorubidus Daunorubicin producing strain purchased from CICC CICC 11043 S. coeruleorubidus -Δdnr Streptomyces coeruleorubidus with disruption of daunorubicin BGC

Streptomyces is well known for synthesis of many biologically active secondary metabolites, such as polyketides and non-ribosomal peptides.Understanding the coupling mechanisms of primary and secondary metabolism can help develop strategies to improve secondary metabolite production in Streptomyces. In this work, Streptomyces albus ZD11, an oil-preferring industrial Streptomyces strain, was proved to have a remarkable capability to generate abundant acyl-CoA precursors for salinomycin biosynthesis with the aid of its enhanced β-oxidation pathway. It was found that the salinomycin biosynthetic gene cluster contains a predicted 3-hydroxyacyl-CoA dehydrogenase (FadB3), which is the third enzyme of β-oxidation cycle. Deletion of fadB3 significantly reduced the production of salinomycin. A variety of experimental evidences showed that FadB3 was mainly involved in the β-oxidation pathway rather than ethylmalonyl-CoA biosynthesis and played a very important role in regulating the rate of β-oxidation in S. albus ZD11. Our findings elucidate an interesting coupling mechanism by which a PKS biosynthetic gene cluster could regulate the β-oxidation pathway by carrying β-oxidation genes, enabling Streptomyces to efficiently synthesize target polyketides and economically utilize environmental nutrients.