Identification and <i>in situ</i> removal of an inhibitory intermediate to develop an efficient phytosterol bioconversion process using a cyclodextrin-resting cell system

Da, Wang; Zhang, Jian; Cao, Dandan; Wang, Xuedong; Wei, Dongzhi

doi:10.1039/d1ra02774c

Cited by 7 publications

(3 citation statements)

References 22 publications

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“…The in-depth influence of detergents on the synthesis of steroids at the metabolic level is worth exploring. In addition to these results, propionyl-CoA, ROS, and 4-ene-3-ketosteroids were identified as toxic molecules that inhibit the synthesis of 9α-OH-AD, and an in-situ adsorption scheme improved the production efficiency by 23.15% (Wang et al 2021 ). Development of omics not only rapidly promoted the technological development of the biosynthesis of steroids, but also provided genetic data for constructing efficient pathways and designing biological cell factories.…”

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

confidence: 98%

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: 98%

Rational development of mycobacteria cell factory for advancing the steroid biomanufacturing

Wang

Liu

et al. 2022

World J Microbiol Biotechnol

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“…In Actinobacteria, the degradation of sterols begins with the oxidation of the β-hydroxyl group of cholesterol, catalyzed by either cholesterol oxidase (ChO) or 3-hydroxysteroid dehydrogenase (3-HSD), leading to the formation of cholest-4-en-3-one (Figure 3) [58][59][60]. Subsequently, through the combined action of 3-ketosteroid-∆1-dehydrogenase (KstD) and 3-sterone-9α-hydroxylase (Ksh), the B-ring of the steroid nucleus undergoes cleavage, eventually resulting in the degradation of products into short-chain organic molecules like propionyl-CoA and propionate [50,61].…”

Section: Reconstructing the Degradation Pathway Of Steroid Nucleusmentioning

confidence: 99%

Green Manufacturing of Steroids via Mycolicbacteria: Current Status and Development Trends

Zhao,

Li,

Xiong

et al. 2023

Fermentation

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Steroids, the second largest drug category ranked after antibiotics, find widespread use in treatments for reproductive health, endocrine regulation, and inflammation. Advances in steroidal chemistry to date have led to the widespread use of sterols as starting substances in the development of environmentally friendly biotechnologies for steroid production, including biocatalysis, microbial transformations, and biosynthesis using engineered micro-organisms. In this review, we synthesize some of the recent advancements in steroid biocatalysis using the Mycolicibacterium species, including the identification and modification of crucial elements for enhanced production. We also delve into the detailed characterization and reconstruction of metabolic pathways in specific microbial strains, shedding light on their potential for steroid biosynthesis. Additionally, we highlight the development of innovative de novo biosynthesis pathways for steroids within engineered cell factories. These results collectively provide an overview of the current landscape and emerging trends in green steroid manufacturing within the steroidal pharmaceutical industry.

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“…However, with the further increase of SSL, the yields decreased; and no ADD was generated when the ratio of SSL/phytosterols reached 4:1. Hence, SSL as co-solvent could not enhance the ADD biosynthesis of the perlite-immobilized M. neoaurum R. Resins were employed as adsorbents for steroids in several researches on steroid biotransformation (Molchanova et al 2007;Wang et al 2021). In fermentation medium containing the equal amount of macroporous resin HPD826 as phytosterols, ADD reached 1.11 g/L, which was 60.9% higher than that in media without HPD826.…”

Section: Optimization Of Add Accumulation By Immobilized M Neoaurum Rmentioning

confidence: 99%

Immobilization of rough morphotype Mycolicibacterium neoaurum R for androstadienedione production

Zhao,

Li,

et al. 2023

Biotechnol Lett

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Enhance androstadienedione (Androst-1,4-diene-3,17-dione, ADD) production of rough-type morphotype Mycolicibacterium neoaurum variant by repeated-batch fermentation of immobilized cells. ResultsM. neoaurum R was a rough colony morphotype variant, obtained from routine plating of smooth M. neoaurum strain CICC 21097. M. neoaurum R showed rougher cell surface and aggregated in broth. The ADD production of M. neoaurum R was notably lower than that of M. neoaurum CICC 21097 during the free cell fermentation, but the yield gap could be erased after proper cell immobilization. Subsequently, repeated-batch fermentation by immobilized M. neoaurum R was performed to shorten the production cycle and enhance the bio-production e ciency of ADD. Through the optimization of the immobilization carriers and the solvents for phytosterols, the ADD productivity of M. neoaurum R immobilized by semiexpanded perlite reached 0.075 g/L/h during the repeated-batch fermentation for 40 days. ConclusionsAlthough smooth strains that could homogenously suspended in broth seemed to be preferred in the steroid bioconversion, the rough-type strain M. neoaurum R might be able to nd their place by proper cell immobilization.

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Identification and in situ removal of an inhibitory intermediate to develop an efficient phytosterol bioconversion process using a cyclodextrin-resting cell system

Abstract: We identified an inhibitory intermediate, 4-ene-3-keto steroids, that limits the bioconversion rate and provided a solution based on resin adsorption for improving 9α-OH-AD production efficiency in a commercial-scale process.

Cited by 7 publications

References 22 publications

Rational development of mycobacteria cell factory for advancing the steroid biomanufacturing

Rational development of mycobacteria cell factory for advancing the steroid biomanufacturing

Green Manufacturing of Steroids via Mycolicbacteria: Current Status and Development Trends

Immobilization of rough morphotype Mycolicibacterium neoaurum R for androstadienedione production

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