Single nucleotide polymorphism analysis for the production of valuable steroid intermediates in Mycobacterium neoaurum

Liu, Min; Zhu, Zhan‐Tao; Tao, Xinyi; Wang, Fengqing; Wei, Dongzhi

doi:10.1007/s10529-016-2187-z

Cited by 3 publications

(4 citation statements)

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“…Genome and transcriptome sequencing can reveal the gene expression changes that may be responsible for steroid catabolism of M. neoaurum . On the basis of significant differences in omics data, combined with single nucleotide polymorphisms and dynamic sRNA data, we can understand gene associations and interactions, as well as the regulatory mechanism of small molecules in various pathways, such as lipid transport and metabolism, amino acid metabolism, signal transduction, cell envelope function and ATP biosynthesis (Liu et al 2016a , b ). For example, a high yield and substrate resistant mutation of M. neoaurum MN4 was obtained by physical and chemical mutagenesis and screening.…”

Section: Significance Of Monooxygenase Resources For Steroid Modifica...mentioning

confidence: 99%

Rational development of mycobacteria cell factory for advancing the steroid biomanufacturing

Wang

Liu

et al. 2022

World J Microbiol Biotechnol

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Steroidal resource occupies a vital proportion in the pharmaceutical industry attributing to their important therapeutic effects on fertility, anti-inflammatory and antiviral activities. Currently, microbial transformation from phytosterol has become the dominant strategy of steroidal drug intermediate synthesis that bypasses the traditional chemical route. Mycobacterium sp. serve as the main industrial microbial strains that are capable of introducing selective functional modifications of steroidal intermediate, which has become an indispensable platform for steroid biomanufacturing. By reviewing the progress in past two decades, the present paper concentrates mainly on the microbial rational modification aspects that include metabolic pathway editing, key enzymes engineering, material transport pathway reinforcement, toxic metabolic intermediates removal and byproduct reconciliation. In addition, progress on omics analysis and direct genetic manipulation are summarized and classified that may help reform the industrial hosts with more efficiency. The paper provides an insightful present for steroid biomanufacturing especially on the current trends and prospects of mycobacteria.

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Section: Significance Of Monooxygenase Resources For Steroid Modifica...mentioning

confidence: 99%

Rational development of mycobacteria cell factory for advancing the steroid biomanufacturing

Wang

Liu

et al. 2022

World J Microbiol Biotechnol

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“…For example, a deep understanding of the enzymatic steps involved into the sterol side-chain degradation could be useful for the design of new AD/ADD-producing strains that do not accumulate the intermediates 4-HBC/1,4-HBC. In order to further understand the regulatory mechanisms of sterol catabolism and steroid production, several transcriptomic and proteomic studies have been also done in recent years, increasingly focused on higher-producer strains (Liu et al, 2016a , b ; Xiong et al, 2017a , b ).…”

Section: Current Challenges Of Steroid Biotechnologymentioning

confidence: 99%

New Insights on Steroid Biotechnology

2018

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Nowadays steroid manufacturing occupies a prominent place in the pharmaceutical industry with an annual global market over $10 billion. The synthesis of steroidal active pharmaceutical ingredients (APIs) such as sex hormones (estrogens, androgens, and progestogens) and corticosteroids is currently performed by a combination of microbiological and chemical processes. Several mycobacterial strains capable of naturally metabolizing sterols (e.g., cholesterol, phytosterols) are used as biocatalysts to transform phytosterols into steroidal intermediates (synthons), which are subsequently used as key precursors to produce steroidal APIs in chemical processes. These synthons can also be modified by other microbial strains capable of introducing regio- and/or stereospecific modifications (functionalization) into steroidal molecules. Most of the industrial microbial strains currently available have been improved through traditional technologies based on physicochemical mutagenesis and selection processes. Surprisingly, Synthetic Biology and Systems Biology approaches have hardly been applied for this purpose. This review attempts to highlight the most relevant research on Steroid Biotechnology carried out in last decades, focusing specially on those works based on recombinant DNA technologies, as well as outlining trends and future perspectives. In addition, the need to construct new microbial cell factories (MCF) to design more robust and bio-sustainable bioprocesses with the ultimate aim of producing steroids à la carte is discussed.

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“…There are a number of organisms known to transform phytosterols to AD such as Aspergillus, Arthrobacter, Bacillus, Brevibacterium, Chryseobacterium, Fusarium, Gordonia, Nocardia, Pseudomonas, Rhodococcus, Streptomyces and Mycobacterium sp. [2,3].…”

Section: Biotransformation and Substrates Usedmentioning

confidence: 99%

“…AD is a compound specifically used as a precursor for the majority of pharmaceutically active steroids such as testosterone, estradiol, ethinylestradiol, testolactone, progesterone, cortisone, cortisol, prednisone and prednisolone [1]. The steroid pharmaceuticals are of great importance for their role in the management of human fertility, osteoporosis, menopause and blood pressure regulation [2,3]. Commercially, steroid production represents one of the largest sectors of medical products manufactured by the pharmaceutical industry [4].…”

Section: Introductionmentioning

confidence: 99%

Microbial Biotransformation for the Production of Steroid Medicament

Rokade¹,

Ravindran²,

Singh³

et al. 2018

Secondary Metabolites - Sources and Applications

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Androstenedione (AD) is a steroid intermediate valuable for the production of steroid medicaments. Microbial biotransformation of phytosterol to produce AD is a wellresearched area. However, low substrate solubility of phytosterol in aqueous media and nucleus degradation of AD to androstadienedione (ADD) or 9-hydroxy-AD are the major obstacles for AD production leading to detailed research for optimization of biotransformation process. In this review, microbial transformation of AD with respect to the existing methods of chemical or biochemical synthesis of AD are extensively discussed. This review examines the microbial biotransformation process and limitations for enhanced AD production. Factors affecting the effective biotransformation process to obtain AD are discussed and limitations are highlighted. The main content of this review focuses on the recent and futuristic biotechnological advances and strategies in techniques to enhance AD bioprocess.

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Single nucleotide polymorphism analysis for the production of valuable steroid intermediates in Mycobacterium neoaurum

Abstract: The work facilitates the understanding of underlying genetic changes that may be responsible for steroid accumulation in M. neoaurum and is useful for its targeted genetic engineering.

Cited by 3 publications

References 14 publications

Rational development of mycobacteria cell factory for advancing the steroid biomanufacturing

Rational development of mycobacteria cell factory for advancing the steroid biomanufacturing

New Insights on Steroid Biotechnology

Microbial Biotransformation for the Production of Steroid Medicament

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