LeTetR Positively Regulates 3-Hydroxylation of the Antifungal HSAF and Its Analogs in Lysobacter enzymogenes OH11

Yu, Lingjun; Khetrapal, Vimmy; Liu, Fengquan; Du, Liangcheng

doi:10.3390/molecules25102286

Cited by 3 publications

(3 citation statements)

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“…5). 89 Deletion of Le TetR resulted in significant reduction of HSAF and alteramides, while the production of their biosynthetic precursors, 3-deOH HSAF and 3-deOH alteramides, was barely affected. This is an interesting finding as it implies that Le TetR selectively regulates the final step of the HSAF biosynthetic pathway, namely, the 3-hydroxylation of 3-deOH-HSAF.…”

Section: Natural Products From Lysobactermentioning

confidence: 97%

Biosynthesis, regulation, and engineering of natural products from Lysobacter

et al. 2022

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Section: Natural Products From Lysobactermentioning

confidence: 97%

Biosynthesis, regulation, and engineering of natural products from Lysobacter

et al. 2022

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“…At present, HSAF can be produced only by Lysobacter , and its biosynthetic gene cluster and synthesis mechanism have been gradually revealed 6,7 . The biosynthetic genes of HSAF include a single module of PKS/NRPS, arginase, 5 redox enzymes, and sterol desaturation/fatty acid hydroxylase 9–11 . To date, HSAF has not been synthesized by chemical means, and L. enzymogenes is one of the few strains that can produce HSAF.…”

Section: Introductionmentioning

confidence: 99%

“… 6 , 7 The biosynthetic genes of HSAF include a single module of PKS/NRPS, arginase, 5 redox enzymes, and sterol desaturation/fatty acid hydroxylase. 9 , 10 , 11 To date, HSAF has not been synthesized by chemical means, and L. enzymogenes is one of the few strains that can produce HSAF. The regulatory mechanism of HSAF biosynthesis and how to improve the yield of HSAF are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Developing a new treatment for superficial fungal infection using antifungal Collagen‐HSAF dressing

Zhong

Yan

Zuo

et al. 2022

Bioengineering & Transla Med

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Fungal pathogens are common causes of superficial clinical infection. Their increasing drug resistance gradually makes existing antifungal drugs ineffective. Heat stable antifungal factor (HSAF) is a novel antifungal natural product with a unique structure. However, the application of HSAF has been hampered by very low yield in the current microbial producers and from extremely poor solubility in water and common solvents. In this study, we developed an effective mode of treatment applying HSAF to superficial fungal infections. The marine‐derived Lysobacter enzymogenes YC36 contains the HSAF biosynthetic gene cluster, which we activated by the interspecific signaling molecule indole. An efficient extraction strategy was used to significantly improve the purity to 95.3%. Scanning electron microscopy images revealed that the Type I collagen‐based HSAF (Col‐HSAF) has a transparent appearance and good physical properties, and the in vitro sustained‐release effect of HSAF was maintained for more than 2 weeks. The effective therapeutic concentration of Col‐HSAF against superficial fungal infection was explored, and Col‐HSAF showed good biocompatibility, lower clinical scores, mild histological changes, and antifungal capabilities in animals with Aspergillus fumigatus keratitis and cutaneous candidiasis. In conclusion, Col‐HSAF is an antifungal reagent with significant clinical value in the treatment of superficial fungal infections.

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TetR and OmpR family regulators in natural product biosynthesis and resistance

Patil,

Sharma,

Bhaskarwar

et al. 2023

Proteins

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This article provides a comprehensive review and sequence‐structure analysis of transcription regulator (TR) families, TetR and OmpR/PhoB, involved in specialized secondary metabolite (SSM) biosynthesis and resistance. Transcription regulation is a fundamental process, playing a crucial role in orchestrating gene expression to confer a survival advantage in response to frequent environmental stress conditions. This process, coupled with signal sensing, enables bacteria to respond to a diverse range of intra and extracellular signals. Thus, major bacterial signaling systems use a receptor domain to sense chemical stimuli along with an output domain responsible for transcription regulation through DNA‐binding. Sensory and output domains on a single polypeptide chain (one component system, OCS) allow response to stimuli by allostery, that is, DNA‐binding affinity modulation upon signal presence/absence. On the other hand, two component systems (TCSs) allow cross‐talk between the sensory and output domains as they are disjoint and transmit information by phosphorelay to mount a response. In both cases, however, TRs play a central role. Biosynthesis of SSMs, which includes antibiotics, is heavily regulated by TRs as it diverts the cell's resources towards the production of these expendable compounds, which also have clinical applications. These TRs have evolved to relay information across specific signals and target genes, thus providing a rich source of unique mechanisms to explore towards addressing the rapid escalation in antimicrobial resistance (AMR). Here we focus on the TetR and OmpR family TRs, which belong to OCS and TCS, respectively. These TR families are well‐known examples of regulators in secondary metabolism and are ubiquitous across different bacteria, as they also participate in a myriad of cellular processes apart from SSM biosynthesis and resistance. As a result, these families exhibit higher sequence divergence, which is also evident from our bioinformatic analysis of 158 389 and 77 437 sequences from TetR and OmpR family TRs, respectively. The analysis of both sequence and structure allowed us to identify novel motifs in addition to the known motifs responsible for TR function and its structural integrity. Understanding the diverse mechanisms employed by these TRs is essential for unraveling the biosynthesis of SSMs. This can also help exploit their regulatory role in biosynthesis for significant pharmaceutical, agricultural, and industrial applications.

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LeTetR Positively Regulates 3-Hydroxylation of the Antifungal HSAF and Its Analogs in Lysobacter enzymogenes OH11

Cited by 3 publications

References 23 publications

Biosynthesis, regulation, and engineering of natural products from Lysobacter

Biosynthesis, regulation, and engineering of natural products from Lysobacter

Developing a new treatment for superficial fungal infection using antifungal Collagen‐HSAF dressing

TetR and OmpR family regulators in natural product biosynthesis and resistance

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