Heterologous characterization of mechercharmycin A biosynthesis reveals alternative insights into post-translational modifications for RiPPs

Pei, Zeng-Fei; Yang, Min-Jie; Zhang, Kai; Jian, Xiao‐Hong; Tang, Gong‐Li

doi:10.1016/j.chembiol.2021.08.005

Cited by 7 publications

(8 citation statements)

References 44 publications

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“…Thus, the P450 in mechercharmycin biosynthesis (McmI) is expected for the leader and follower peptide dependent β-hydroxylation at Phe after the regioselective dehydration and consecutive heterocyclizations. The β-hydroxylated Phe1 is eventually converted to the unique 5-phenyloxazole via heterocyclization and dehydrogenation, a process which is worthy of further investigation (Figure B) …”

Section: P450s In Other Ripp Biosynthesesmentioning

confidence: 99%

“… a Homologous proteins of TsrP and TsrR are also encoded in the BGCs of siomycin ( 51 ) (ref ), thiopeptin ( 52 ) (refs , ), Sch18640 ( 53 ) (ref ), and saalfelduracin ( 54 ) (ref ). b Homologous proteins of NosB and NosC are also encoded in the BGCs of nocathiacin ( 62 ) (refs , ) and persiathiacin ( 63 ) (ref ). c Homologous proteins of NocV, NocU and NocT are also encoded in the BGC of persiathiacin ( 63 ) (ref ). d Homologous proteins of McmI are also encoded in the BGCs of YM-216391 ( 121 ) (ref ), aurantizolicin ( 122 ) (ref ), and curacozole ( 123 ) (ref ). …”

Section: Introductionmentioning

confidence: 99%

“… d Homologous proteins of McmI are also encoded in the BGCs of YM-216391 ( 121 ) (ref ), aurantizolicin ( 122 ) (ref ), and curacozole ( 123 ) (ref ). …”

Section: Introductionmentioning

confidence: 99%

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Cytochromes P450 Associated with the Biosyntheses of Ribosomally Synthesized and Post-translationally Modified Peptides

Zhong

2023

ACS Bio Med Chem Au

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Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a class of exponentially increased natural products with characteristic chemical structures, topologies, and biosynthetic mechanisms as well as exceptional bioactivities including antibacteria, antitumors, and antiviruses. The biosynthesis of RiPP proceeds via a ribosomally assembled precursor peptide that undergoes varied post-translational modifications to generate a mature peptide. Cytochrome P450 (CYP or P450) monooxygenases are a superfamily of heme-containing enzymes that span a wide range of secondary metabolite biosynthetic pathways due to their broad substrate scopes and excellent catalytic versatility. In contrast to the enormous quantities of RiPPs and P450s, the P450 associated RiPP biosynthesis is comparatively limited, with most of their functions and timings remaining mysterious. Herein, this Review aims to provide an overview on the striking roles of P450s in RiPP biosyntheses uncovered to date and to illustrate their remarkable functions, mechanisms, as well as remaining challenges. This will shed light on novel P450 discovery and characterizations in RiPP biosyntheses.

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Section: P450s In Other Ripp Biosynthesesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cytochromes P450 Associated with the Biosyntheses of Ribosomally Synthesized and Post-translationally Modified Peptides

Zhong

2023

ACS Bio Med Chem Au

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“… Curacozole (Figure ) was isolated from Streptomyces curacoi by genome mining in 2018 which also shares a similar core peptide (FIIGSTCC) with YM-216391 and showed highly toxic toward HCT116 and HOS cancer cell lines with IC 50 values at 8.6 and 10.5 nM respectively (Table ). Two novel congeners MCM 17 and 18 (Figure ) were obtained by expressing engineered mechercharmycin pathway in heterologous host B. subtilis TG1111 and exhibited comparable cytotoxicity against Jurkat cell lines …”

Section: Antitumor Rippsmentioning

confidence: 99%

“… 133 Two novel congeners MCM 17 and 18 ( Figure 18 ) were obtained by expressing engineered mechercharmycin pathway in heterologous host B. subtilis TG1111 and exhibited comparable cytotoxicity against Jurkat cell lines. 134 …”

Section: Antitumor Rippsmentioning

confidence: 99%

Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides

Zhong

Wang

Yan

et al. 2022

ACS Bio Med Chem Au

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Ribosomally synthesized and post-translationally modified peptides (RiPPs) are of increasing interest in natural products as well as drug discovery. This empowers not only the unique chemical structures and topologies in natural products but also the excellent bioactivities such as antibacteria, antifungi, antiviruses, and so on. Advances in genomics, bioinformatics, and chemical analytics have promoted the exponential increase of RiPPs as well as the evaluation of biological activities thereof. Furthermore, benefiting from their relatively simple and conserved biosynthetic logic, RiPPs are prone to be engineered to obtain diverse analogues that exhibit distinct physiological activities and are difficult to synthesize. This Review aims to systematically address the variety of biological activities and/or the mode of mechanisms of novel RiPPs discovered in the past decade, albeit the characteristics of selective structures and biosynthetic mechanisms are briefly covered as well. Almost one-half of the cases are involved in anti-Gram-positive bacteria. Meanwhile, an increasing number of RiPPs related to anti-Gram-negative bacteria, antitumor, antivirus, etc., are also discussed in detail. Last but not least, we sum up some disciplines of the RiPPs' biological activities to guide genome mining as well as drug discovery and optimization in the future.

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Rational Engineering of Secondary Metabolic Pathways in a Heterologous Host to Enable the Biosynthesis of Hibarimicin Derivatives with Enhanced Anti-Melanomic Activity

Liu,

Zhao,

Tian

et al. 2024

Engineering

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Heterologous characterization of mechercharmycin A biosynthesis reveals alternative insights into post-translational modifications for RiPPs

Cited by 7 publications

References 44 publications

Cytochromes P450 Associated with the Biosyntheses of Ribosomally Synthesized and Post-translationally Modified Peptides

Cytochromes P450 Associated with the Biosyntheses of Ribosomally Synthesized and Post-translationally Modified Peptides

Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides

Rational Engineering of Secondary Metabolic Pathways in a Heterologous Host to Enable the Biosynthesis of Hibarimicin Derivatives with Enhanced Anti-Melanomic Activity

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