Dataset Information

Nitric Oxide and Hydrogen Peroxide Signaling in Extractive Shiraia Fermentation by Triton X-100 for Hypocrellin A Production.

ABSTRACT: Shiraia mycelial culture is a promising biotechnological alternative for the production of hypocrellin A (HA), a new photosensitizer for anticancer photodynamic therapy (PDT). The extractive fermentation of intracellular HA in the nonionic surfactant Triton X-100 (TX100) aqueous solution was studied in the present work. The addition of 25 g/L TX100 at 36 h of the fermentation not only enhanced HA exudation to the broth by 15.6-fold, but stimulated HA content in mycelia by 5.1-fold, leading to the higher production 206.2 mg/L, a 5.4-fold of the control on day 9. After the induced cell membrane permeabilization by TX100 addition, a rapid generation of nitric oxide (NO) and hydrogen peroxide (H2O2) was observed. The increase of NO level was suppressed by the scavenger vitamin C (VC) of reactive oxygen species (ROS), whereas the induced H2O2 production could not be prevented by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), suggesting that NO production may occur downstream of ROS in the extractive fermentation. Both NO and H2O2 were proved to be involved in the expressions of HA biosynthetic genes (Mono, PKS and Omef) and HA production. NO was found to be able to up-regulate the expression of transporter genes (MFS and ABC) for HA exudation. Our results indicated the integrated role of NO and ROS in the extractive fermentation and provided a practical biotechnological process for HA production.

SUBMITTER: Li XP

PROVIDER: S-EPMC7037624 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Nitric Oxide and Hydrogen Peroxide Signaling in Extractive <i>Shiraia</i> Fermentation by Triton X-100 for Hypocrellin A Production.

Li Xin Ping XP Wang Yue Y Ma Yan Jun YJ Wang Jian Wen JW Zheng Li Ping LP

International journal of molecular sciences 20200130 3

<i>Shiraia</i> mycelial culture is a promising biotechnological alternative for the production of hypocrellin A (HA), a new photosensitizer for anticancer photodynamic therapy (PDT). The extractive fermentation of intracellular HA in the nonionic surfactant Triton X-100 (TX100) aqueous solution was studied in the present work. The addition of 25 g/L TX100 at 36 h of the fermentation not only enhanced HA exudation to the broth by 15.6-fold, but stimulated HA content in mycelia by 5.1-fold, leadin ...[more]

PMID: 32019072

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Project description:Hydrogen peroxide (H2O2) and nitric oxide (NO·) are toxic metabolites that immune cells use to attack pathogens. These antimicrobials can be present at the same time in phagosomes, and it remains unclear how bacteria deal with these insults when simultaneously present. Here, using Escherichia coli, we observed that simultaneous exposure to H2O2 and NO· leads to prioritized detoxification, where enzymatic removal of NO· is impeded until H2O2 has been eliminated. This phenomenon is reminiscent of carbon catabolite repression (CCR), where preferred carbon sources are catabolized prior to less desirable substrates; however, H2O2 and NO· are toxic, growth-inhibitory compounds rather than growth-promoting nutrients. To understand how NO· detoxification is delayed by H2O2 whereas H2O2 detoxification proceeds unimpeded, we confirmed that the effect depended on Hmp, which is the main NO· detoxification enzyme, and used an approach that integrated computational modeling and experimentation to delineate and test potential mechanisms. Plausible interactions included H2O2-dependent inhibition of hmp transcription and translation, direct inhibition of Hmp catalysis, and competition for reducing equivalents between Hmp and H2O2-degrading enzymes. Experiments illustrated that Hmp catalysis and NAD(P)H supply were not impaired by H2O2, whereas hmp transcription and translation were diminished. A dependence of this phenomenon on transcriptional regulation parallels CCR, and we found it to involve the transcriptional repressor NsrR. Collectively, these data suggest that bacterial regulation of growth inhibitor detoxification has similarities to the regulation of growth substrate consumption, which could have ramifications for infectious disease, bioremediation, and biocatalysis from inhibitor-containing feedstocks.IMPORTANCE Bacteria can be exposed to H2O2 and NO· concurrently within phagosomes. In such multistress situations, bacteria could have evolved to simultaneously degrade both toxic metabolites or preferentially detoxify one over the other. Here, we found that simultaneous exposure to H2O2 and NO· leads to prioritized detoxification, where detoxification of NO· is hampered until H2O2 has been eliminated. This phenomenon resembles CCR, where bacteria consume one substrate over others in carbon source mixtures. Further experimentation revealed a central role for transcriptional regulation in the prioritization of H2O2 over NO·, which is also important to CCR. This study suggests that regulatory scenarios observed in bacterial consumption of growth-promoting compound mixtures can be conserved in bacterial detoxification of toxic metabolite mixtures.

Dataset Information

Nitric Oxide and Hydrogen Peroxide Signaling in Extractive Shiraia Fermentation by Triton X-100 for Hypocrellin A Production.

Publications

Nitric Oxide and Hydrogen Peroxide Signaling in Extractive <i>Shiraia</i> Fermentation by Triton X-100 for Hypocrellin A Production.

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