Efficient Ilamycins Production Utilizing Enteromorpha Prolifera by Metabolically Engineered Streptomyces Atratus

Overview

Journal Biotechnol Biofuels Bioprod

Publisher Biomed Central

Date 2023 Oct 5

PMID 37798770

Authors

Yu-Xi Jiang

Gao-Fan Zheng

Long-Chao Chen

Na Yang

Xiu-Juan Xin

Jun-Ying Ma

Jian-Hua Ju

Hui Wu

Ming Zhao

Ruida Wang

Fa-Liang An

Affiliations

Soon will be listed here.

Abstract

With the invasion of green tides and the increase of urban green areas worldwide, multimillion tons of Enteromorpha need to be reutilized. In this study, Enteromorpha prolifera powder is considered a promising biomass resource for the production of commercial chemical products production. Ilamycins, novel cyclic heptapeptides with significant anti-TB activities, are isolated from Streptomyces atratus SCSIO ZH16, a deep-sea-derived strain. Using EP powder as a nitrogen source, the production of ilamycins reached 709.97 mg/L through optimization of the nitrogen source using the engineered strain S. atratus SCSIO ZH16 ΔR. After mutant strain constructions and tests, strain S. atratus SCSIO ZH16 ΔR::bldD EP powder achieved a higher production titer of ilamycins. Furthermore, the production titer of ilamycins and ilamycin E reached 1561.77 mg/L and 745.44 mg/L, respectively, in a 5 L bioreactor. This study suggests that E. prolifera is a promising and eco-friendly nitrogen source for the production of ilamycins.

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References

Wang R, Kong F, Wu H, Hou B, Kang Y, Cao Y . Complete genome sequence of high-yield strain B48 and identification of crucial mutations contributing to lincomycin overproduction. Synth Syst Biotechnol. 2020; 5(2):37-48. PMC: 7160387. DOI: 10.1016/j.synbio.2020.03.001. View

Bu Q, Li Y, Xie H, Li J, Lv Z, Su Y . Rational engineering strategies for achieving high-yield, high-quality and high-stability of natural product production in actinomycetes. Metab Eng. 2021; 67:198-215. DOI: 10.1016/j.ymben.2021.06.003. View

Del Carratore F, Hanko E, Breitling R, Takano E . Biotechnological application of Streptomyces for the production of clinical drugs and other bioactive molecules. Curr Opin Biotechnol. 2022; 77:102762. DOI: 10.1016/j.copbio.2022.102762. View

Cuebas-Irizarry M, Grunden A . Streptomyces spp. as biocatalyst sources in pulp and paper and textile industries: Biodegradation, bioconversion and valorization of waste. Microb Biotechnol. 2023; 17(1):e14258. PMC: 10832569. DOI: 10.1111/1751-7915.14258. View

Makitrynskyy R, Tsypik O, Nuzzo D, Paululat T, Zechel D, Bechthold A . Secondary nucleotide messenger c-di-GMP exerts a global control on natural product biosynthesis in streptomycetes. Nucleic Acids Res. 2020; 48(3):1583-1598. PMC: 7026642. DOI: 10.1093/nar/gkz1220. View

Yan H, Lu X, Sun D, Zhuang S, Chen Q, Chen Z . BldD, a master developmental repressor, activates antibiotic production in two Streptomyces species. Mol Microbiol. 2019; 113(1):123-142. DOI: 10.1111/mmi.14405. View

Zhou Q, Ning S, Luo Y . Coordinated regulation for nature products discovery and overproduction in . Synth Syst Biotechnol. 2020; 5(2):49-58. PMC: 7176746. DOI: 10.1016/j.synbio.2020.04.002. View

Schalchli H, Hormazabal E, Astudillo A, Briceno G, Rubilar O, Diez M . Bioconversion of potato solid waste into antifungals and biopigments using Streptomyces spp. PLoS One. 2021; 16(5):e0252113. PMC: 8139487. DOI: 10.1371/journal.pone.0252113. View

Yan X, Zhang B, Tian W, Dai Q, Zheng X, Hu K . Puromycin A, B and C, cryptic nucleosides identified from NRRL B-1832 by PPtase-based activation. Synth Syst Biotechnol. 2018; 3(1):76-80. PMC: 5884247. DOI: 10.1016/j.synbio.2018.02.001. View

10.

Sun C, Yang Z, Zhang C, Liu Z, He J, Liu Q . Genome Mining of Streptomyces atratus SCSIO ZH16: Discovery of Atratumycin and Identification of Its Biosynthetic Gene Cluster. Org Lett. 2019; 21(5):1453-1457. DOI: 10.1021/acs.orglett.9b00208. View

11.

Huang H, Zheng G, Jiang W, Hu H, Lu Y . One-step high-efficiency CRISPR/Cas9-mediated genome editing in Streptomyces. Acta Biochim Biophys Sin (Shanghai). 2015; 47(4):231-43. DOI: 10.1093/abbs/gmv007. View

12.

Fan Z, Tong N, Zhuang Z, Ma C, Ma J, Ju J . Medium optimization and subsequent fermentative regulation enabled the scaled-up production of anti-tuberculosis drug leads ilamycin-E1/E2. Biotechnol J. 2022; 17(4):e2100427. DOI: 10.1002/biot.202100427. View

13.

Zhu Y, Zheng G, Xin X, Ma J, Ju J, An F . Combinatorial strategies for production improvement of anti-tuberculosis antibiotics ilamycins E/E from deep sea-derived Streptomyces atratus SCSIO ZH16 ΔilaR. Bioresour Bioprocess. 2024; 9(1):111. PMC: 10992044. DOI: 10.1186/s40643-022-00599-z. View

14.

Yang Z, Wei X, He J, Sun C, Ju J, Ma J . Characterization of the Noncanonical Regulatory and Transporter Genes in Atratumycin Biosynthesis and Production in a Heterologous Host. Mar Drugs. 2019; 17(10). PMC: 6835768. DOI: 10.3390/md17100560. View

15.

Zhao S, Li P, Fang H, Song L, Li D, Liu R . Enhancement methane fermentation of Enteromorpha prolifera waste by Saccharomyces cerevisiae: batch kinetic investigation, dissolved organic matter characterization, and synergistic mechanism. Environ Sci Pollut Res Int. 2020; 27(14):16254-16267. DOI: 10.1007/s11356-020-08013-x. View

16.

Beld J, Sonnenschein E, Vickery C, Noel J, Burkart M . The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life. Nat Prod Rep. 2013; 31(1):61-108. PMC: 3918677. DOI: 10.1039/c3np70054b. View

17.

Ma J, Huang H, Xie Y, Liu Z, Zhao J, Zhang C . Biosynthesis of ilamycins featuring unusual building blocks and engineered production of enhanced anti-tuberculosis agents. Nat Commun. 2017; 8(1):391. PMC: 5577134. DOI: 10.1038/s41467-017-00419-5. View

18.

Yang Z, Sun C, Liu Z, Liu Q, Zhang T, Ju J . Production of Antitubercular Depsipeptides via Biosynthetic Engineering of Cinnamoyl Units. J Nat Prod. 2020; 83(5):1666-1673. DOI: 10.1021/acs.jnatprod.0c00194. View

19.

Chng C, Lum A, Vroom J, Kao C . A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea. Proc Natl Acad Sci U S A. 2008; 105(32):11346-51. PMC: 2516264. DOI: 10.1073/pnas.0803622105. View

20.

Overland M, Mydland L, Skrede A . Marine macroalgae as sources of protein and bioactive compounds in feed for monogastric animals. J Sci Food Agric. 2018; 99(1):13-24. PMC: 6585948. DOI: 10.1002/jsfa.9143. View