Crystallomycin revisited after 60 years: aspartocins B and C

Anton P Tyurin; Vera A Alferova; Alexander S Paramonov; Maxim V Shuvalov; Irina A Malanicheva; Natalia E Grammatikova; Pavel N Solyev; Shaowei Liu; Chenghang Sun; Igor A Prokhorenko; Tatyana A Efimenko; Larisa P Terekhova; Olga V Efremenkova; Zakhar O Shenkarev; Vladimir A Korshun

doi:10.1039/c8md00002f

Crystallomycin revisited after 60 years: aspartocins B and C

Medchemcomm. 2018 Feb 27;9(4):667-675. doi: 10.1039/c8md00002f. eCollection 2018 Apr 1.

Authors

Anton P Tyurin^{1

2}, Vera A Alferova¹, Alexander S Paramonov², Maxim V Shuvalov^{1

3}, Irina A Malanicheva¹, Natalia E Grammatikova¹, Pavel N Solyev⁴, Shaowei Liu⁵, Chenghang Sun⁵, Igor A Prokhorenko^{1

2}, Tatyana A Efimenko¹, Larisa P Terekhova¹, Olga V Efremenkova¹, Zakhar O Shenkarev^{2

6}, Vladimir A Korshun^{1

2}

Affiliations

¹ Gause Institute of New Antibiotics , B. Pirogovskaya 11 , Moscow 119021 , Russia . Email: v-korshun@yandex.ru.
² Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry , Miklukho-Maklaya 16/10 , Moscow 117997 , Russia . Email: zakhar-shenkarev@yandex.ru.
³ Department of Chemistry , Lomonosov Moscow State University , 1-3 Leninskie Gory , Moscow 119992 , Russia.
⁴ Engelhardt Institute of Molecular Biology , Vavilova 32 , Moscow 119991 , Russia.
⁵ Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences & Peking Union Medical College , Tian Tan Xi Li 1 , Beijing 100050 , China.
⁶ Moscow Institute of Physics and Technology , Institutsky lane 9, Dolgoprydny , Moscow region 141700 , Russia.

Abstract

The study of an archived sample of crystallomycin complex using HPLC, ESI HRMS, and 2D NMR showed that two major components of the antibiotic, compounds 1 and 2, are lipopeptides having the same peptide core, Asp1-cyclo(Dab2-Pip3-MeAsp4-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11-), N-acylated either with Δ³-iso-tetradecenoyl or Δ³-anteiso-pentadecenoyl that are identical to aspartocins C and B, respectively. According to the 2D NMR study, compound 2 in DMSO solution exists as a mixture of four conformers. The producing strain was identified as Streptomyces griseorubens. Compounds 1 and 2 have considerable Ca²⁺-dependent activity against Gram-positive bacteria including five MRSA strains.